Vasoconstrictor effects of endothelin-1 on myocardium microcirculation studied by the Langendorff perfusion method: differential sensitivities among microvessels.
An intravital fluorescence microscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in the isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Changes in diameters of coronary microvessels accompanying the cumulative injection of ET-1 in the perfusate were observed and recorded with a video camera system. Coronary perfusion pressure was also measured during each experiment. Bolus injections of ET-1 (1-300 pmole) elicited a dose-dependent increase in perfusion pressure from 54 +/- 6 mm Hg (mean +/- SEM; n = 10, before the ET-1 injection) to 144 +/- 9 mm Hg (n = 8, at the ET-1 dose of 300 pmole). A dose-dependent narrowing of microvessels was also observed. This vasoconstriction was especially prominent in small-sized arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles (P less than 0.05). The response induced by ET-1 dose of 3-10 pmole was significantly larger in arterioles than in postcapillary venules in the diameter range between 10 and 40 microns. The vasoconstriction produced by ET-1 was inhomogeneous. Some part of bifurcations of arterioles showed a prominent localized vasoconstriction, and occasionally showed a complete luminal obstruction. Such a segmental vasospasm might be attributed to localized sensitivities of arterioles to ET-1. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in the myocardium.
Homma
S
S
Department of Biomedical Engineering, University of Tsukuba, Ibaraki, Japan.
Miyauchi
T
T
Sugishita
Y
Y
Goto
K
K
Sato
M
M
Ohshima
N
N
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006339:Heart Rate; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D010477:Perfusion; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014699:Venules / Q000187:drug effects
D016232:Endothelins