Chronic endothelin-induced pressor and renal actions in conscious dogs do not require altered ANG II formation.
Plasma endothelin levels are elevated approximately two- to threefold in a number of chronic pathophysiological conditions associated with hypertension. Results from recent studies indicate an important interaction between endothelin and the renin-angiotensin system (RAS). The role of the RAS in mediating the increases in arterial pressure produced by long-term pathophysiological elevations in circulating levels of endothelin is unknown. Therefore, the purpose of this study was to chronically increase circulating levels of endothelin within the pathophysiological range and determine the long-term cardiovascular and renal actions of endothelin in control dogs (n = 6) and in dogs pretreated with a converting-enzyme inhibitor (CEI) (n = 6) or CEI + angiotensin II (ANG II) replacement (n = 6). Infusion of endothelin-1 for 8 days at a rate of 2.5 ng.kg-1.min-1 increased plasma endothelin from 7.1 +/- 0.9 to 19.8 +/- 3.3 pg/ml. In control dogs, endothelin increased mean arterial pressure (MAP) by 19% (90 +/- 2 to 107 +/- 3 mmHg) while decreasing renal blood flow (RBF) by 30% and glomerular filtration rate (GFR) by 15-20%. Long-term elevation of circulating endothelin produced similar elevations in MAP in dogs pretreated with CEI (+16%) or CEI + ANG II (+17%). Similar decreases in RBF and GFR also occurred in response to endothelin in all three groups. These results indicate that although long-term increases in circulating endothelin within the pathophysiological range produce significant increases in arterial pressure, this effect does not appear to be mediated by the RAS.
Wilkins
F C
FC
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216.
Kassab
S
S
Kato
T
T
Mizelle
H L
HL
Opgenorth
T J
TJ
Granger
J P
JP
D000804:Angiotensin II / Q000096:biosynthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D004338:Drug Combinations; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D004338:Drug Combinations; D016232:Endothelins; D006728:Hormones; D000804:Angiotensin II; D002216:Captopril