Differing actions of endothelin-1 on canine systemic resistance and capacitance vessels.
In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1 (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase; phase 1), followed by a continuous elevation of blood pressure (late hypertensive phase; phase 2). The constriction and dilation of the systemic capacitance and resistance vessels were evaluated from the change in mean circulatory pressure (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the modification of the action of ET-1 on the blood vessels by the baroceptor reflex or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1, we performed experiments in dogs under total spinal anesthesia (TSA group), methylene blue-treated dogs (MB group) as well as in the untreated dogs (control group). ET-1 decreased the TPR significantly, and increased the MCP significantly in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference between the groups. ET-1 had no significant effect on TPR but increased the MCP significantly in MB group (n = 8) during phase 1. The percentage increase of MCP in the MB group significantly exceeded that of the control group. ET-1 increased both the TPR and MCP significantly in phase 2 in the control group (n = 8). This study indicated that the vasoconstrictor action of ET-1 on the systemic capacitance vessels in phase 1 did not result from a baroceptor reflex, and that the vasodilator action of ET-1 on the systemic resistance vessels may be at least in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator action of EDRF on the systemic capacitance vessels is weak.
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
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K
Takai
H
H
Ito
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T
Sahashi
H
H
Wada
T
T
Segawa
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S
Hirakawa
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006439:Hemodynamics / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D016232:Endothelins; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D008751:Methylene Blue