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• W126366915 abstract "Nitric oxide (NO) produced by the endothelium diffuses into the vascular smooth muscle, where it activates soluble guanylyl cyclase (sGC); the resultant increase in cyclic guanosine monophosphate (cGMP) causes vasodilation of the resistance arteries through modulation of calcium channels and by decreasing the calcium sensitivity of the vascular smooth muscle contractile proteins (1). The response to guanylyl cyclase activation is terminated by enzymatic hydrolysis of cGMP. Coronary artery vascular smooth muscle cGMP-hydrolyzing activity is mainly the result of phosphodiesterase-1 (PDE1), a calmodulin-dependent PDE, and PDE5, which is a calcium-calmodulin independent cGMP-specific PDE (2). Of the total cGMP hydrolyzing activity, PDE1 constituted 73% in porcine and approximately 80% in bovine normal epicardial coronary artery (3). Vinpocetin, a selective inhibitor PDE1, has been shown to cause concentration-dependent relaxation of isolated arterial vessel segments (4). Similarly, the PDE5 inhibitors zaprinast, E4021, and sildenafil caused relaxation of isolated porcine or canine normal epicardial coronary artery segments in vitro that was associated with an increase of vascular cGMP concentration (5–7). Comparable results have been obtained in vivo where E4021, 10 µg/kg/min iv, a dose that produced no change in aortic pressure, caused epicardial coronary artery dilation in awake pigs with a 2.9 ± 0.5% increase in coronary diameter (6). The findings indicate that selective inhibition of either PDE1 or PDE5 alone can cause an increase in coronary cGMP content with resultant vasodilation and imply that either PDE pathway alone may be insufficient to maintain normal cGMP levels. It should be noted that these findings apply to epicardial coronary arteries, and that measurements of PDE activity and cGMP content in coronary resistance vessels (where blood flow is regulated) are not available." @default.
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• W126366915 date "2004-01-01" @default.
• W126366915 modified "2023-09-23" @default.
• W126366915 title "Effect of Phosphodiesterase-5 Inhibition on Coronary Blood Flow in Experimental Animals" @default.
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• W126366915 doi "https://doi.org/10.1007/978-1-59259-748-2_10" @default.
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