title: Effects of low doses of endothelin-1 on basal vascular tone and autoregulatory vasodilation in canine coronary microcirculation in vivo.
abstract: 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 > or =10(-11) mol/L constricted coronary arterioles (< or =100 microm in diameter) and small arteries (>100 microm 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 > or =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.
authors.affiliation: The First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Kanatsuka
authors.forename: K
authors.initials: K
authors.lastname: Akai
authors.forename: A
authors.initials: A
authors.lastname: Sugimura
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.forename: T
authors.initials: T
authors.lastname: Komaru
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000818:Animals; D001158:Arteries; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001784:Blood Gas Analysis; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002550:Cerebral Veins / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D019332:Endothelin-1