Renal vasoconstriction by the endothelial cell-derived peptide endothelin in spontaneously hypertensive rats.
The effects of endothelin on systemic and renal hemodynamics in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were examined. Endothelin (500 ng i.v. +1,000 ng/hr per 300-g rat) elevated mean blood pressure by 13% (p less than 0.02) and decreased renal blood flow by 71% and glomerular filtration rate by 66% (both p less than 0.01), resulting in a 430% (p less than 0.05) increase in renal vascular resistance (RVR) in SHR. This rise in blood pressure was associated with a significant increase in hematocrit (+8%), but a decrease in urinary sodium excretion (-51%). This dose of endothelin reduced cardiac output by 40% (p less than 0.001) and brought about a 96% (p less than 0.01) rise in systemic vascular resistance (SVR). However, the SVR increase was significantly smaller than the RVR increase. These changes in systemic and renal hemodynamics were observed in a dose-dependent manner, and the degrees of change did not differ between the two strains. Additional infusion of atrial natriuretic peptide (0.33 microgram/kg/min) into SHR completely reversed the changes in blood pressure and renal hemodynamics caused by endothelin, resulting in pronounced natriuresis (+760%). The renal vascular casting study revealed that endothelin mainly constricted the arcuate and interlobular arteries, as well as afferent arterioles. These results suggest that endothelin may be involved in blood pressure and body fluid volume regulation through systemic and renal vasoconstriction.
Hirata
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Matsuoka
H
H
Kimura
K
K
Fukui
K
K
Hayakawa
H
H
Suzuki
E
E
Sugimoto
T
T
Sugimoto
T
T
Yanagisawa
M
M
Masaki
T
T
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction
D016232:Endothelins; D010455:Peptides