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 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^-8mol/L) was superfused onto the epimyocardium in a cumulative fashion. In another set of dogs (n=l6), the perfusion pressure of the observed vascular bed was reduced to 60mmHg (mild stenosis) and to 40mmHg (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 (≤100μm in diameter) and small arteries (>100μm 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 than the pathophysiological plasma level, increases the basal vascular tone, but does not attenuate the autoregulatory vasodilation of the coronary microcirculation.