Matches in SemOpenAlex for { <https://semopenalex.org/work/W2029226821> ?p ?o ?g. }
- W2029226821 endingPage "1100" @default.
- W2029226821 startingPage "1081" @default.
- W2029226821 abstract "Cyclic nucleotide phosphodiesterases (PDEs) comprise at least seven families of isozymes coded by related but distinct genes, grouped on the basis of their structural and enzymatic characteristics. Five of these families are known to be present in the cardiovascular system. A number of potent inhibitors have been synthesised with relative selectivity for some PDEs. However, there is no selective inhibitor of PDE1 (calmodulin-activated), and only one compound has been reported which selectively inhibits PDE2 (stimulated by cGMP). Available information is limited to pharmacological and therapeutic properties of drugs selectively inhibiting two PDEs specific for cAMP (PDE3, inhibited by milrinone-like cardiotonics, and PDE4, inhibited by rolipram) and a cGMP-PDE (PDE5, inhibited by zaprinast). Differential expression of PDEs and differential subcellular localisation provide the possibility of selectively targeting cardiovascular and platelet functions with selective PDE inhibitors. The resulting effects include short- and long-term modulation of cardiac and vascular inotropy, cardiac rhythm and exoitability, thrombosis, inflammatory responses to injury and, probably, proliferation of vascular smooth muscle cells. PDE3 inhibitors have been investigated in heart failure. Despite leading to marked haemodynamic improvement, chronic treatment with PDE3 inhibitors does not increase (and may even decrease) survival, due to arrhythmias (probably induced by excessive cAMP accumulation). PDE4 inhibitors are being actively investigated in inflammatory diseases. Their actions in endothelial cells may also lead to antithrombotic effects. PDE5 inhibitors might compensate the pathological impairment of nitric oxide-induced cGMP levels seen in atherosclerosis and after endothelial injury. Preclinical studies suggest that they may reduce myointimal proliferation after angioplasty. Identification of isozymes expressed in each tissue and determination of their possible pathological alterations will probably be possible in the near future. This will afford clarification of the role of PDEs in the cardiovascular system and the potential therapeutic uses of PDE inhibitors." @default.
- W2029226821 created "2016-06-24" @default.
- W2029226821 creator A5067044709 @default.
- W2029226821 creator A5082015327 @default.
- W2029226821 creator A5084001156 @default.
- W2029226821 creator A5086042397 @default.
- W2029226821 date "1995-11-01" @default.
- W2029226821 modified "2023-09-25" @default.
- W2029226821 title "Section Review: Cardiovascular & Renal: Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiovascular diseases" @default.
- W2029226821 cites W110557356 @default.
- W2029226821 cites W1486274077 @default.
- W2029226821 cites W1505892934 @default.
- W2029226821 cites W1510098440 @default.
- W2029226821 cites W1531734841 @default.
- W2029226821 cites W1558386025 @default.
- W2029226821 cites W1566938829 @default.
- W2029226821 cites W1575601729 @default.
- W2029226821 cites W1580526233 @default.
- W2029226821 cites W1855637366 @default.
- W2029226821 cites W187129005 @default.
- W2029226821 cites W1875395090 @default.
- W2029226821 cites W1964002039 @default.
- W2029226821 cites W1965071737 @default.
- W2029226821 cites W1965753603 @default.
- W2029226821 cites W1965987256 @default.
- W2029226821 cites W1968133040 @default.
- W2029226821 cites W1974675539 @default.
- W2029226821 cites W1974821785 @default.
- W2029226821 cites W1976187561 @default.
- W2029226821 cites W1977177612 @default.
- W2029226821 cites W1979604520 @default.
- W2029226821 cites W1982492319 @default.
- W2029226821 cites W1982677020 @default.
- W2029226821 cites W1985084727 @default.
- W2029226821 cites W1985416654 @default.
- W2029226821 cites W1988408001 @default.
- W2029226821 cites W1991339741 @default.
- W2029226821 cites W1991369800 @default.
- W2029226821 cites W1991706389 @default.
- W2029226821 cites W1992084443 @default.
- W2029226821 cites W1997624464 @default.
- W2029226821 cites W1998154155 @default.
- W2029226821 cites W1999874899 @default.
- W2029226821 cites W2009114097 @default.
- W2029226821 cites W2013039234 @default.
- W2029226821 cites W2018168922 @default.
- W2029226821 cites W2020726609 @default.
- W2029226821 cites W2024881120 @default.
- W2029226821 cites W2026256311 @default.
- W2029226821 cites W2027778775 @default.
- W2029226821 cites W2027825091 @default.
- W2029226821 cites W2031048595 @default.
- W2029226821 cites W2036246796 @default.
- W2029226821 cites W2036687660 @default.
- W2029226821 cites W2037404641 @default.
- W2029226821 cites W2038422814 @default.
- W2029226821 cites W2039266436 @default.
- W2029226821 cites W2042531223 @default.
- W2029226821 cites W2042836765 @default.
- W2029226821 cites W2047242707 @default.
- W2029226821 cites W2047354087 @default.
- W2029226821 cites W2048990297 @default.
- W2029226821 cites W2049804330 @default.
- W2029226821 cites W2052098549 @default.
- W2029226821 cites W2053132471 @default.
- W2029226821 cites W2053805288 @default.
- W2029226821 cites W2055698980 @default.
- W2029226821 cites W2058217093 @default.
- W2029226821 cites W2060306792 @default.
- W2029226821 cites W2061579073 @default.
- W2029226821 cites W2062020346 @default.
- W2029226821 cites W2064514516 @default.
- W2029226821 cites W2065215622 @default.
- W2029226821 cites W2066739500 @default.
- W2029226821 cites W2067043353 @default.
- W2029226821 cites W2068137401 @default.
- W2029226821 cites W2069411481 @default.
- W2029226821 cites W2071437372 @default.
- W2029226821 cites W2071590869 @default.
- W2029226821 cites W2072728865 @default.
- W2029226821 cites W2074212602 @default.
- W2029226821 cites W2075603196 @default.
- W2029226821 cites W2080766468 @default.
- W2029226821 cites W2080955714 @default.
- W2029226821 cites W2081123642 @default.
- W2029226821 cites W2082834057 @default.
- W2029226821 cites W2085847022 @default.
- W2029226821 cites W2087933068 @default.
- W2029226821 cites W2092004001 @default.
- W2029226821 cites W2092996139 @default.
- W2029226821 cites W2099441694 @default.
- W2029226821 cites W2101873472 @default.
- W2029226821 cites W2107732949 @default.
- W2029226821 cites W2110960164 @default.
- W2029226821 cites W2114497687 @default.
- W2029226821 cites W2125141239 @default.
- W2029226821 cites W2126711789 @default.
- W2029226821 cites W2136297988 @default.