Abnormal renal medullary response to angiotensin II in SHR is corrected bylong-term enalapril treatment

This study tested the hypotheses that renal medullary blood flow (MBF) in s pontaneously hypertensive rats (SHR) has enhanced responsiveness to angiote nsin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not alt ered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced do se 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 sen sitivity in WKY rats while L-arginine given into the renal medulla abolishe d the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enal april (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 infu sed into the renal medulla. Endothelium-dependent vasodilation (assessed wi th aortic rings) was significantly greater in treated SHR when compared wit h 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 c ounterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensi tivity of MBF to ANG II. These effects may be causally related to the persi stent antihypertensive action of enalapril in SHR.