Effects of low doses of endothelin-1 on basal vascular tone and autoregulatory vasodilation in canine coronary microcirculation in vivo

The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affe ct vascular tone and autoregulatory vasodilation during a reduction in perf usion pressure in the coronary microcirculation in vivo. In anesthetized op en-chest dogs, arterial microvessels in the epimyocardium were observed thr ough 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. Tn another set of dogs (n=16), the perfusion pressure of the obser ved vascular bed was reduced to 60 mmHg (mild stenosis) and to 40 mmHg (sev ere 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 greater than or equal to 10(-11) mol/L constricted coronary arterioles (less than or equal to 100 mu m in diameter) and small arteries (>100 mu m 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 arter ioles and small arteries before and during the mild and severe stenosis. Ho wever, ET-1 did not attenuate the percentage dilation of arterioles from th e baseline in response to the mild and severe stenosis. The data indicates the following: (1) ET-1 at doses greater than or equal to 10(-11) mol/L sim ilarly constricts coronary arterioles and small arteries; (2) ET-1 at 10(-1 1) mol/L, which is slightly higher than the pathophysiological plasma level , increases the basal vascular tone, but does not attenuate the autoregulat ory vasodilation of the coronary microcirculation.