Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.
The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.
Braun
C
C
5th Department of Medicine (Nephrology/Endocrinology), University of Heidelberg, Klinikum der Stadt Mannheim, Germany.
Lang
C
C
Hocher
B
B
Gretz
N
N
van der Woude
F J
FJ
Rohmeiss
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000077300:Bosentan; D004353:Drug Evaluation, Preclinical; D016232:Endothelins / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology*; D007672:Kidney Cortex / Q000098:blood supply; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000502:physiology*; D012083:Renin / Q000097:blood; D013449:Sulfonamides / Q000627:therapeutic use
D000959:Antihypertensive Agents; D016232:Endothelins; D013449:Sulfonamides; D012083:Renin; D000077300:Bosentan