SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2050358509> ?p ?o ?g. }

Showing items 1 to 100 of ±131 with 100 items per page.

W2050358509 endingPage "312" @default.
W2050358509 startingPage "307" @default.
W2050358509 abstract "HomeHypertensionVol. 53, No. 2Sympathetic Activity, Vascular Capacitance, and Long-Term Regulation of Arterial Pressure Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBSympathetic Activity, Vascular Capacitance, and Long-Term Regulation of Arterial Pressure Gregory D. Fink Gregory D. FinkGregory D. Fink From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing. Search for more papers by this author Originally published29 Dec 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.119990Hypertension. 2009;53:307–312Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 29, 2008: Previous Version 1 I am honored to have been chosen to present the 2008 Arthur C. Corcoran Memorial Lecture, because Dr Corcoran was both a brilliant scientist and one of the founding fathers in the field of hypertension research, but I am particularly gratified to join the list of superb scientists who have preceded me as Corcoran lecturers.When I began studying hypertension as a postdoctoral fellow, under the tutelage of Dr Michael Brody at the University of Iowa, I quickly acquired what turned out to be a lifelong interest in the integrative aspects of cardiovascular system regulation. Because of Dr Brody’s research interests, this naturally included a focus on the sympathetic nervous system. However, a major stimulus for my fascination with integrative physiology was the excitement at that time over the detailed and refined mathematical model of the circulation developed by Arthur Guyton, Thomas Coleman, and colleagues at the University of Mississippi.1 It is well known of course that the model highlights the importance of body fluid volume regulation as the key determinant of long-term arterial pressure regulation. The combined impact of these 2 influences—at a formative stage in my research career—led to my deep interest in the following question: “Can the sympathetic nervous system participate in long-term arterial pressure regulation within the framework of the Guyton-Coleman circulatory model?” Guyton and colleagues incorporated sympathetic regulation into their model. They emphasized the importance of nonrenal sympathetic activity in determining the hemodynamic pattern of many forms of hypertension and the potential for renal sympathetic nerve activity to affect the renal function curve (pressure-natriuresis relationship) and to thereby help establish the long-term value of arterial pressure. However, they also pointed out the tendency of reflex mechanisms regulating sympathetic activity to reset and, thus, maintain sympathetic activity at normal levels. This would minimize the influence of sympathetic activity on the regulation of arterial pressure. Evidence has accumulated over the last few decades, however, based on a variety of methods in experimental animals and humans, that sympathetic nervous system activity is chronically increased (albeit modestly) in at least a subset of hypertensive individuals.2–4 This has led to a renewed interest in how sympathetic nervous system activity—renal and nonrenal—influences the circulation in hypertension. In this review, I discuss theoretical and experimental evidence for the importance of one nonrenal effect of sympathetic activity in explaining the pathophysiology of hypertension.Mechanisms of Long-Term Control of Arterial Pressure by the Sympathetic Nervous SystemSympathetic nervous system activity can elevate arterial pressure by augmenting the force and/or rate of cardiac contraction; decreasing the diameter of resistance arteries; and reducing sodium and water excretion by the kidneys. Within the conceptual framework of the Guyton-Coleman model, however, only 1 of these actions can exert a major effect on the long-term level of arterial pressure. Because pressure-natriuresis is presumed to have infinite gain over the long term within the hierarchy of circulatory control mechanisms,5 the ability of efferent renal sympathetic nerve activity to shift the pressure-natriuresis relationship to higher pressures,6 directly or indirectly (eg, through renin release), is of paramount importance. If this were the only physiological effect of sympathetic activation, the results would be sodium and water retention, blood volume expansion, and increased arterial pressure. There is good evidence supporting an important role for renal sympathetic activity in the pathophysiology of hypertension. Renal denervation lowers resting arterial pressure and also attenuates the development of hypertension in numerous experimental models.7–9 Furthermore, sympathetic activity at rest is quite low and is only increased ≈50% in hypertension4,10; and renal tubules and juxtaglomerular cells respond to significantly lower sympathetic firing rates than do resistance arteries.11 Thus, it is quite plausible that moderately increased sympathetic nerve activity causes hypertension by affecting renal sodium and water excretion.Nevertheless, there are some problems with this concept. First, although the majority of published studies report an effect of renal denervation on hypertension development,7 this is not uniformly the case.12,13 Second, evidence linking renal sympathetic activity to chronic changes in sodium excretion or total circulating blood volume in hypertension is also conflicting.14–16 Third, although expansion of total blood volume alone can increase arterial pressure and account for chronic hypertension under some circumstances,17,18 in general there is an inverse relationship between arterial pressure and total blood volume, across the spectrum from abnormally low to abnormally high pressures.19–21Vascular Capacitance and Arterial Pressure RegulationIf arterial pressure is not always directly related to total blood volume, then exactly how does this volume-based control system work? Guyton and colleagues1 recognized that hypertension is manifested through a wide variety of distinct hemodynamic patterns and showed clearly how changes in, eg, total peripheral resistance brought on by myogenic or local vascular control mechanisms (autoregulation), vasoconstrictor hormones, or sympathetic nervous system activity could produce an elevated steady-state arterial pressure associated with normal or even low total blood volumes, as long as the pressure-natriuresis mechanism was shifted to a higher pressure level.1,5Another key factor built into their model—and the focus of this review—is the “blood holding capacity” of the circulation, ie, the vascular capacitance. Simply put, it is evident that pressure within a closed but compliant fluid containing system will be determined by both the total contained fluid volume and by the fluid-holding capacity (dimensions) of the system. Although blood is held to some extent in all parts of the cardiovascular system (heart, lung, arteries, veins, etc), ≈70% of total blood volume is contained in systemic veins.22,23 This is because veins have much thinner walls and larger lumen diameters than do arteries. Therefore, the compliance (Δ stored volume/Δ distending pressure) and capacitance (volume at a given internal pressure) of veins (at low internal pressures) are very large relative to that of arteries (venous compliance is estimated to be 30 times greater than arterial compliance in humans24), ie, overall vascular capacitance is largely determined by the structure and function of veins. There is less smooth muscle in the wall of veins than in arteries, but sufficient muscle exists in all but the very smallest veins to actively regulate wall tension and venous diameter.22,23 Therefore, even quite modest alterations in smooth muscle tone (eg, venoconstriction) can dramatically affect the amount of blood stored within veins.In the Guyton-Coleman model, changes in venous capacitance (in addition to total peripheral resistance) were understood to play a part in determining the hemodynamic pattern of hypertension, including the association of high arterial pressure with low total blood volume.1,5 They considered vascular capacitance primarily in terms of its impact on steady-state blood flow through the circulation (venous return and cardiac output). Recently, a new synthesis has been developed that focuses on blood volume redistribution (driven by transient flow changes) from vascular regions of differing compliances as the most critical circulatory response to alterations in vascular capacitance. Detailed explanations of this conceptual scheme are found in the works of Tyberg,25 Brengelmann,26 and Reddi and Carpenter.27 The ideas developed by these individuals complement the theory of Schrier28 that also highlights the importance of blood volume distribution in cardiovascular regulation. In particular, Schrier28 has noted that the term “effective blood volume,” often used to explain apparently anomalous relationships between total blood volume and arterial pressure, more accurately refers to the amount of blood in the arterial circulation only. Thus, redistribution of blood from the venous to the arterial system can increase effective blood volume, even when total blood volume is reduced.28The venous system can be considered as 2 compartments, because its capacitance function is not invested equally in all parts of the venous circulation.24 Relative capacitance of the 3 major compartments of the systemic circulation (arterial, peripheral venous, and central venous) are 5%, 80%, and 15%, respectively, of total vascular capacitance (estimated to be 175 mL/mm Hg for a 70-kg human).26 The very compliant peripheral venous compartment (mostly composed of veins within the splanchnic region) stores the great majority (≈60%) of blood in the circulation. However, it is the far smaller volume of blood (≈10%) in the less compliant central venous compartment (composed of the thoracic vena cava and other great veins) that is especially critical to circulatory dynamics.26,27 A decrease in peripheral compartment capacitance affects arterial pressure because it causes venous return to transiently exceed cardiac output, thereby increasing central compartment blood volume. Volumes of blood ≤10% of total intravascular volume can be transferred into the central circulation in this fashion.29 As central blood volume increases, cardiac filling rises, and the Frank-Starling mechanism causes more blood to be ejected into the very low compliance arterial system. Of course, the precise magnitude, pattern, and duration of circulatory changes caused by alterations in vascular capacitance will depend on the effectiveness of baroreflex, renal, hormonal, and other counterregulatory responses to altered blood volume in the various vascular compartments. For example, the impact of increased central compartment volume on arterial pressure likely depends on the following: (1) the efficiency of the heart’s transfer of blood into the arterial system; (2) arterial system compliance; and (3) the ways in which the kidney and arteriolar resistance vessels respond to increased arterial system filling. It is essential to note that, within the framework of the Guyton-Coleman model, reduced vascular capacitance alone would be incapable of causing a sustained increase in arterial pressure unless the pressure-natriuresis relationship also was shifted to a higher pressure level. In the model, such a shift would require additional external neural or humoral influences on the kidney. Other investigators have proposed, however, that such a shift may be attributable simply to rapid resetting of the pressure-natriuresis relationship in response to changes in renal perfusion pressure.30–33 Some studies, however, provide evidence against resetting of the pressure-natriuresis relationship.34Vascular Capacitance and HypertensionThe hallmark hemodynamic change in established hypertension clearly is increased vascular resistance. However, in human subjects with established hypertension, total systemic and specifically venous capacitance also are reduced.35 Decreased vascular capacitance is most marked in the veins outside the central compartment35–37 and is particularly notable in the splanchnic circulation.38 Central redistribution of blood volume is observed in young or borderline hypertensive patients while total blood volume is normal.37,39–41 In established hypertension, central blood volume is near normal, but total blood volume is reduced.37,41–43 Very similar results (ie, increased central but not total blood volumes) have been reported in experimental hypertension in animals.44,45 Thus, redistribution of circulating blood without a change in its total volume could be an important aspect of the hemodynamics of hypertension.A helpful example of the potential impact of blood volume distribution on arterial pressure is the phenomenon of supine hypertension observed in patients with peripheral autonomic failure.46 Although most such patients have abnormally low blood pressure while standing, ≈50% develop marked hypertension when they are supine. Why do some patients exhibit supine hypertension whereas other do not? One obvious possible explanation is that the hypertensive patients have a higher total blood volume, perhaps because of a greater propensity of their kidneys to retain sodium and water. However, no correlation was found between total blood volume and blood pressure in these patients.46 An alternative explanation is as follows. Blood pressure is low when the patients are upright because gravity pulls blood into the lower parts of the body, where it is stored in the highly compliant veins, particularly in the splanchnic organs. This constitutes a reduction in effective blood volume. When the patients move to the supine position, gravitational forces are negated, and blood is transferred back toward the central circulation. This increases effective blood volume and arterial blood pressure. Support for this scenario is provided by the fact that 3 treatments, head-up tilt, nitroglycerin, and sildenafil, known to be effective in treating supine hypertension,47,48 cause either venodilation or a redistribution of blood from central to peripheral compartments. Selective arterial vasodilators, on the other hand, are generally ineffective.48Finally, it deserves mention that redistributing blood from the central compartment to the highly compliant splanchnic vasculature (peripheral compartment) leads to a chronic reduction in arterial blood pressure in association with increased total blood volume, even in individuals with sustained hypertension. For example, portal vein ligation normalizes arterial pressure in spontaneously hypertensive rats49; and the onset of portal hypertension in patients with hepatic cirrhosis and essential hypertension also can produce dramatic decreases in arterial pressure.50Sympathetic Nervous System and Vascular Capacitance in HypertensionSmall veins and venules in the splanchnic region make up the bulk of the peripheral venous compartment and also exhibit the highest degree of active venoconstriction.51–53 Therefore, factors regulating venomotor tone in these vessels are critical in determining active changes in capacitance. Sympathetic venoconstrictor activity is quantitatively the most important determinant of venomotor tone in splanchnic veins54,55 and of venomotor tone in the entire circulation.56,57 Like the renal tubules, veins respond to much lower frequencies of sympathetic nerve activity than do arteries.58,59 Therefore, it seems reasonable to hypothesize that moderately increased sympathetic nervous system activity could contribute to the development of hypertension by reducing vascular capacitance. This scenario was previously proposed explicitly for human hypertension,60 and substantial supporting animal data exist.61–63 In the last section of this brief review, I discuss in more detail theoretical and experimental evidence supporting the importance of sympathetic control of vascular capacitance in 1 specific form of hypertension, ie, angiotensin-dependent hypertension.Angiotensin-Dependent HypertensionAlthough there are abundant data from humans and experimental animals showing that the renin-angiotensin system participates in the development of hypertension, the precise mechanisms involved remain in dispute. A very convincing case can be made that direct actions of angiotensin II within the kidney are of particular importance,64 without any necessary contribution from actions of angiotensin II outside the kidney. Here I marshal evidence, however, for reduced vascular capacitance as a plausible alternative, or possibly complementary, mechanism.Drs Guyton and Coleman obviously were not the only researchers who constructed a mathematical model of the circulation. Luetscher and colleagues in 1973 published a detailed, computer-based, mathematical model of the human circulation that particularly focused on how the renin-angiotensin system contributes to arterial pressure regulation.65 Importantly, their model emphasized the potential for the autonomic nervous system to affect long-term blood pressure regulation. The article included the results of impressive simulations demonstrating that the model could very accurately reproduce many features of the human circulation. What conclusions did these investigators draw about the development of renin-dependent hypertension based on their model? First, “It is not necessary to assume that blood volume is increased.” Second, “Cardiac output is enhanced by adrenergic activity … and supported by increased venous return from contracted peripheral capacitance vessels.” Other attempts to explain disordered arterial pressure regulation with the use of circulatory models have also emphasized the potentially important role of changes in venous compliance or capacitance.66,67 Thus, there is theoretical support for the notion that a sympathetically mediated reduction in vascular capacitance occurs in angiotensin-dependent hypertension.In 1980, Young et al68 published an experimental analysis of the hemodynamic basis of chronic angiotensin II–induced hypertension in the dog. Among the many variables hat they measured was mean circulatory filling pressure (MCFP). When combined with measurements of blood volume, MCFP provides a good estimate of overall circulatory capacitance or compliance, properties determined for the most part by the smooth muscle tone of veins. They concluded that, “In this form of hypertension, the increase in arterial pressure was achieved without volume expansion and cardiac output elevation, but with large initial increases in arterial and venous vascular tone.” Two years later, additional studies on angiotensin-induced hypertension in the dog were published.69 These investigators focused their attention on the quantitative relationships between segmental body fluid volumes and the hemodynamics of angiotensin-induced hypertension. They concluded the following: “ … about half of the rise in blood pressure during angiotensin infusion is due to increased end-diastolic volume caused by blood redistribution. About 2/3 of this increase in preload is due to redistribution from the splanchnic bed … ” Therefore, experimental evidence also supports the idea that reduced vascular capacitance, particularly in the splanchnic region, participates in angiotensin-dependent hypertension.None of the studies cited up to now, however, directly addressed the question of whether changes in vascular capacitance are a cause of angiotensin-dependent hypertension. Recently, Dr Andrew King and I70 undertook studies to investigate changes in vascular capacitance in an experimental model of hypertension in which chronic angiotensin II infusion is combined with either normal (0.4% NaCl) or high (2.0% NaCl) dietary salt intake in the rat. Vascular capacitance was determined using serial measurements of blood volume and MCFP in conscious rats. One advantage of the model is that increased sympathetic nervous system activity is evident during angiotensin II infusion in animals on high but not normal salt intake.71 This allows investigation of 2 mechanistically distinct forms of angiotensin-dependent hypertension. Hypertension is more severe in animals on the high-salt diet. We found increased venoconstriction during angiotensin II infusion only in rats on the high-salt diet. To investigate the mechanism of this venoconstriction, we measured acute changes in MCFP in response to ganglion blockade with hexamethonium. The magnitude of the acute fall in MCFP during ganglion blockade was unchanged during angiotensin II infusion in rats on normal salt intake but significantly increased in rats on a high-salt diet. We concluded that, under certain circumstances (in this case, a high-salt diet), sympathetically mediated venoconstriction occurs in angiotensin-dependent hypertension. The question that these results do not answer, however, is: does sympathetic venoconstriction play a part in causing angiotensin II–salt hypertension?Experiments we performed to determine whether sympathetic venoconstriction caused hypertension in rats receiving a high-salt diet, and angiotensin II infusions focused on the sympathetic innervation of the splanchnic region.72 As discussed earlier, splanchnic veins contain a substantial fraction of the circulating blood volume; and that blood is readily mobilized into the central circulation by low levels of sympathetic nerve activity. Splanchnic sympathetic nerve activity has been reported to be increased in angiotensin-induced hypertension in rats.73 Finally, surgical section of the splanchnic sympathetic nerves was an early (and generally successful) treatment for hypertension in human patients.74 The method that we chose to achieve splanchnic sympathetic denervation was to remove the celiac ganglion plexus, which supplies the majority of sympathetic innervation to the splanchnic region. We confirmed the effectiveness of denervation by measuring norepinephrine content in various splanchnic organs. The main finding of our study was that sympathetic denervation of the splanchnic region significantly attenuated, but did not fully prevent, hypertension development during chronic angiotensin II infusion in rats on a high-salt diet. Importantly, the increased venoconstriction (presumably for the most part splanchnic) that normally occurs in this model of hypertension was abolished by splanchnic sympathetic denervation. Only a small portion of sympathetic innervation to the kidney passes through the celiac ganglion in the rat.75,76 However, to confirm that the effect of celiac ganglionectomy was not attributed to removing renal sympathetic innervation, we showed that selective renal denervation alone did not attenuate hypertension development during chronic angiotensin II infusion in rats on a high-salt diet.72 Another recent study in rabbits also showed no effect of renal denervation on angiotensin-induced hypertension.12 Finally, we found that splanchnic denervation had no influence on hypertension development in rats receiving a normal salt diet and angiotensin II infusion. We concluded that sympathetically mediated splanchnic venoconstriction is one, but obviously not the only, cause of hypertension in angiotensin-dependent hypertension.PerspectivesMy overall conclusions are that venous smooth muscle tone and vascular capacitance contribute to long-term blood pressure regulation and that this is one important mechanism by which elevated sympathetic nervous system activity can lead to hypertension. One attractive aspect of this idea is its congruence with the large body of data showing a weak or even inverse relationship between total blood volume and arterial blood pressure, although additional mechanisms also can account for this phenomenon, as discussed earlier. It also helps explain some other characteristics commonly found in hypertensive individuals, such as exaggerated increases in cardiac output and natriuresis during acute volume loading. What are some additional implications?First, because of the finite blood storing capacity of the peripheral venous compartment, blood volume redistribution can affect arterial pressure level only over a limited range of blood volumes. The gain of this pressure control mechanism, therefore, is limited, especially under conditions associated with substantial blood volume excess or deficit. Second, vascular capacitance is merely one component of a complex, interacting regulatory network, as highlighted in detailed mathematical models of the circulatory control system. One important function of capacitance regulation within that network is probably modulating the gain of other control mechanisms. For example, as noted by Guyton et al,1 reduced vascular capacitance could markedly amplify the hemodynamic effects of renal sodium and water retention. Third, experimental and clinical findings suggest that the impact of sympathetically mediated changes in vascular capacitance may be larger during the development of hypertension than during its sustained phase. Finally, it should be noted that many factors other than the sympathetic nervous system affect venous structure and function and, thus, likely participate in the regulation of vascular capacitance. Examples include endothelin, NO, reactive oxygen species, and other proinflammatory and anti-inflammatory molecules. Capitalizing on the overall concept I’ve presented here to develop new approaches to cardiovascular therapy targeting capacitance regulation will require a more thorough understanding of all of the factors affecting venous structure and function.The ideas expressed in this review are those of myself alone. I have benefited from discussions of the topic with many colleagues and students, however, including Dr John Osborn, Dr J.R. Haywood, Dr Andrew King, Dr Melissa Li, and Sachin Kandlikar. The data from my laboratory that I presented were obtained as part of the research program of the Neurogenic Cardiovascular Disease Consortium (Principal Investigator: Dr John Osborn).Sources of FundingThe results discussed from my laboratory were generated with funding from National Institutes of Health grant RO1 HL076312 to the Neurogenic Cardiovascular Disease Consortium. My work comparing the function of arteries and veins also is supported by NHLBI grant PO1 HL070687.DisclosuresNone.FootnotesCorrespondence to Gregory D. Fink, Department of Pharmacology and Toxicology, B440 Life Sciences Building, Michigan State University, East Lansing, MI 48824-1317. E-mail [email protected] References 1 Guyton AC, Coleman TG, Cowley AW Jr, Liard JF, Norman RA Jr, Manning RD Jr. Systems analysis of arterial pressure regulation and hypertension. Ann Biomed Eng. 1972; 1: 254–281.CrossrefMedlineGoogle Scholar2 Grassi G, Quarti-Trevano F, Dell'oro R, Mancia G. Essential hypertension and the sympathetic nervous system. Neurol Sci. 2008; 29 (suppl 1): S33–S36.CrossrefMedlineGoogle Scholar3 Joyner MJ, Charkoudian N, Wallin BG. A sympathetic view of the sympathetic nervous system and human blood pressure regulation. Exp Physiol. 2008; 93: 715–724.CrossrefMedlineGoogle Scholar4 Mary DA, Stoker JB. The activity of single vasoconstrictor nerve units in hypertension. Acta Physiol Scand. 2003; 177: 367–376.CrossrefMedlineGoogle Scholar5 Guyton AC. Kidneys and fluids in pressure regulation. Small volume but large pressure changes. Hypertension. 1992; 19: I2–I8.LinkGoogle Scholar6 Roman RJ, Cowley AW Jr. Characterization of a new model for the study of pressure-natriuresis in the rat. Am J Physiol. 1985; 248: F190–F198.CrossrefMedlineGoogle Scholar7 DiBona GF. Physiology in perspective: the wisdom of the body. Neural control of the kidney. Am J Physiol Regul Integr Comp Physiol. 2005; 289: R633–R641.CrossrefMedlineGoogle Scholar8 Grisk O, Rettig R. Interactions between the sympathetic nervous system and the kidneys in arterial hypertension. Cardiovasc Res. 2004; 61: 238–246.CrossrefMedlineGoogle Scholar9 DiBona GF. Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens. 2002; 11: 197–200.CrossrefMedlineGoogle Scholar10 Macefield VG, Elam M, Wallin BG. Firing properties of single postganglionic sympathetic neurones recorded in awake human subjects. Auton Neurosci. 2002; 95: 146–159.CrossrefMedlineGoogle Scholar11 DiBona GF. Dynamic analysis of patterns of renal sympathetic nerve activity: Implications for renal function. Exp Physiol. 2005; 90: 159–161.CrossrefMedlineGoogle Scholar12 Burke SL, Evans RG, Moretti JL, Head GA. Levels of renal and extrarenal sympathetic drive in angiotensin ii-induced hypertension. Hypertension. 2008; 51: 878–883.LinkGoogle Scholar13 Dzielak DJ, Norman RA Jr. Renal nerves are not necessary for onset or maintenance of doc-salt hypertension in rats. Am J Physiol. 1985; 249: H945–H949.MedlineGoogle Scholar14 Greenberg S, Osborn JL. Relationship between sodium balance and renal innervation during hypertension development in the spontaneously hypertensive rat. J Hypertens. 1994; 12: 1359–1364.MedlineGoogle Scholar15 Lohmeier TE, Hildebrandt DA. Renal nerves promote sodium excretion in angiotensin-induced hypertension. Hypertension. 1998; 31: 429–434.CrossrefMedlineGoogle Scholar16 Winternitz SR, Katholi RE, Oparil S. Role of the renal sympathetic nerves in the development and maintenance of hypertension in the spontaneously hypertensive rat. J Clin Invest. 1980; 66: 971–978.CrossrefMedlineGoogle Scholar17 Saad E, Charra B, Raj DS. Hypertension control with daily dialysis. Semin Dial. 2004; 17:" @default.
W2050358509 created "2016-06-24" @default.
W2050358509 creator A5053076079 @default.
W2050358509 date "2009-02-01" @default.
W2050358509 modified "2023-09-28" @default.
W2050358509 title "Sympathetic Activity, Vascular Capacitance, and Long-Term Regulation of Arterial Pressure" @default.
W2050358509 cites W1509950818 @default.
W2050358509 cites W1798432044 @default.
W2050358509 cites W1893317275 @default.
W2050358509 cites W1968217945 @default.
W2050358509 cites W1969433205 @default.
W2050358509 cites W1969483062 @default.
W2050358509 cites W1973377271 @default.
W2050358509 cites W1973636919 @default.
W2050358509 cites W1977409958 @default.
W2050358509 cites W1978558019 @default.
W2050358509 cites W1982919290 @default.
W2050358509 cites W1985989203 @default.
W2050358509 cites W1992830196 @default.
W2050358509 cites W1993375259 @default.
W2050358509 cites W2001858748 @default.
W2050358509 cites W2003516857 @default.
W2050358509 cites W2005427938 @default.
W2050358509 cites W2008503235 @default.
W2050358509 cites W2009802087 @default.
W2050358509 cites W2010344494 @default.
W2050358509 cites W2012228453 @default.
W2050358509 cites W2013806185 @default.
W2050358509 cites W2017217215 @default.
W2050358509 cites W2021817633 @default.
W2050358509 cites W2023467695 @default.
W2050358509 cites W2027895758 @default.
W2050358509 cites W2027921696 @default.
W2050358509 cites W203738730 @default.
W2050358509 cites W2039602478 @default.
W2050358509 cites W2056748604 @default.
W2050358509 cites W2059330344 @default.
W2050358509 cites W2059665052 @default.
W2050358509 cites W2060435183 @default.
W2050358509 cites W2062485924 @default.
W2050358509 cites W2072471946 @default.
W2050358509 cites W2079792046 @default.
W2050358509 cites W2083426283 @default.
W2050358509 cites W2084042223 @default.
W2050358509 cites W2088125353 @default.
W2050358509 cites W2090052448 @default.
W2050358509 cites W2091856082 @default.
W2050358509 cites W2093922062 @default.
W2050358509 cites W2094746084 @default.
W2050358509 cites W2112154387 @default.
W2050358509 cites W2124111965 @default.
W2050358509 cites W2129343903 @default.
W2050358509 cites W2131177304 @default.
W2050358509 cites W2136694337 @default.
W2050358509 cites W2146300757 @default.
W2050358509 cites W2148071655 @default.
W2050358509 cites W2148473247 @default.
W2050358509 cites W2149964263 @default.
W2050358509 cites W2158265212 @default.
W2050358509 cites W2161838161 @default.
W2050358509 cites W2167154997 @default.
W2050358509 cites W2334435078 @default.
W2050358509 cites W4234423997 @default.
W2050358509 doi "https://doi.org/10.1161/hypertensionaha.108.119990" @default.
W2050358509 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2685147" @default.
W2050358509 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19114645" @default.
W2050358509 hasPublicationYear "2009" @default.
W2050358509 type Work @default.
W2050358509 sameAs 2050358509 @default.
W2050358509 citedByCount "68" @default.
W2050358509 countsByYear W20503585092012 @default.
W2050358509 countsByYear W20503585092013 @default.
W2050358509 countsByYear W20503585092014 @default.
W2050358509 countsByYear W20503585092015 @default.
W2050358509 countsByYear W20503585092016 @default.
W2050358509 countsByYear W20503585092017 @default.
W2050358509 countsByYear W20503585092018 @default.
W2050358509 countsByYear W20503585092019 @default.
W2050358509 countsByYear W20503585092020 @default.
W2050358509 countsByYear W20503585092021 @default.
W2050358509 countsByYear W20503585092022 @default.
W2050358509 countsByYear W20503585092023 @default.
W2050358509 crossrefType "journal-article" @default.
W2050358509 hasAuthorship W2050358509A5053076079 @default.
W2050358509 hasBestOaLocation W20503585091 @default.
W2050358509 hasConcept C121332964 @default.
W2050358509 hasConcept C126322002 @default.
W2050358509 hasConcept C164705383 @default.
W2050358509 hasConcept C2776533406 @default.
W2050358509 hasConcept C2777953023 @default.
W2050358509 hasConcept C3020789104 @default.
W2050358509 hasConcept C58245268 @default.
W2050358509 hasConcept C61797465 @default.
W2050358509 hasConcept C62520636 @default.
W2050358509 hasConcept C71924100 @default.
W2050358509 hasConcept C84393581 @default.
W2050358509 hasConceptScore W2050358509C121332964 @default.
W2050358509 hasConceptScore W2050358509C126322002 @default.