Influence of the renal endothelin A system on the autoregulation of renal hemodynamics in SHRs and WKY rats.
In this study, we investigated the influence of a short-term blockade of the renal endothelin A system on the autoregulation of total renal blood flow, cortical renal blood flow, and pressure-dependent plasma renin activity in spontaneously hypertensive rats (SHRs) and normotensive controls [Wistar-Kyoto (WKY) rats]. In anesthetized rats, renal blood flow was measured by a transit-time flow probe and cortical blood flow by a laser flow probe. Blood samples were taken for measurement of plasma renin activity. Renal perfusion pressure was reduced in 5-mm Hg steps by means of a servocontrolled electropneumatic device by an inflatable suprarenal cuff. During the experiments, the rats (n = 6, each group) received an intrarenal infusion of either the selective endothelin A-receptor antagonist BQ123 (3 mg/kg/h) or vehicle. We observed an improvement of total and cortical blood flow autoregulation as indicated by a shift of lower limits of autoregulation to lower threshold pressures [103 +/- 2 vs. 132 +/- 4 mm Hg compared with 98 +/- 3 vs. 120 +/- 4 mm Hg (mean +/- SEM); p < 0.01 resp. p < 0.05] in BQ123-treated SHRs, whereas BQ123 had no influence on breakpoints of autoregulation in WKY rats (p > 0.05). Pressure-dependent plasma renin activity in SHRs was not influenced by BQ123. Renal blood flow autoregulation is improved in SHRs after short-term blockade of the renal endothelin A system. This effect is independent of the renin-angiotensin system. The endothelin A system does not seem to play an important role in the autoregulation of renal blood flow in normotensive WKY rats.
Braun
C
C
Medical Clinic V (Nephrology/Endocrinology), University Medical Center Mannheim of the University of Heidelberg, Germany.
Lang
C
C
Hocher
B
B
van der Woude
F J
FJ
Rohmeiss
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000097:blood; D006706:Homeostasis; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D012083:Renin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)