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.
Department of Physiology, Medical Sciences Building, University of Western Ontario, London N6A 5C1, Canada.
S A
SA
Dukacz
M G
MG
Feng
L F
LF
Yang
R M
RM
Lee
R L
RL
Kline
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