Effects of Low Doses of Endothelin-1 on Basal Vascular Tone and Autoregulatory Vasodilation in Canine Coronary Microcirculation in Vivo

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The plasma level of endothelin-1(ET-1)increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion pressure in the coronary microcirculation in vivo. In anesthetized open-chest dogs, arterial microvessels in the epimyocardium were observed through a microscope equipped with a floating objective. In 6 dogs, ET-1(10^<-13> to 10^<-8> mol/L)was superfused onto the epimyocardium in a cumulative fashion. In another set of dogs(n=16), the perfusion pressure of the observed vascular bed was reduced to 60 mmHg(mild stenosis)and to 40 mmHg(severe stenosis)by a hydraulic occluder, and the microvascular responses were observed in the presence(n=9)or absence(n=7)of ET-1(10^<-12> or 10^<-11> mol/L). ET-1≥10^<-11> mol/L constricted coronary arterioles(≤100 μm in diameter)and small arteries(>100 μm in diameter)in a dose-dependent fashion. ET-1 of 10^<-12> mol/L affected neither the basal diameters nor the dilation of vessels during the pressure reduction. ET-1 of 10^<-11> mol/L decreased the diameters of arterioles and small arteries before and during the mild and severe stenosis. However, ET-1 did not attenuate the percentage dilation of arterioles from the baseline in response to the mild and severe stenosis. The data indicates the following:(1)ET-1 at doses ≥10^<-11> mol/L similarly constricts coronary arterioles and small arteries;(2)ET-1 at 10^<-11> mol/L, which is slightly higher tnan the pathophysiological plasma level, increases the basal vascular tone, bt does not attenuate the autoregulatory vasodilation of the coronary microcirculation.
社団法人日本循環器学会の論文
1999-07-20

Effects of Low Doses of Endothelin-1 on Basal Vascular Tone and Autoregulatory Vasodilation in Canine Coronary Microcirculation in Vivo

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