Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment.
This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng. kg(-1). min(-1)) in SHR. Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while L-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg. kg(-1). day(-1) when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after L-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.
Dukacz
S A
SA
Department of Physiology, Medical Sciences Building, University of Western Ontario, London N6A 5C1, Canada.
Feng
M G
MG
Yang
L F
LF
Lee
R M
RM
Kline
R L
RL
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester