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1 Department of Physiology, University of Western Ontario, London N6A 5C1; and 2 Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
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 · min1) in SHR.
Infusion of NG-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 · kg1 · day1 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.
endothelial-dependent relaxation; nitric oxide; renal blood flow; blood pressure; vascular hypertrophy
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