NO dependency of RBF and autoregulation in the spontaneously hypertensive rat

Am J Physiol Renal Physiol. 2003 Jul;285(1):F105-12. doi: 10.1152/ajprenal.00348.2002. Epub 2003 Mar 11.

Abstract

In the spontaneously hypertensive rat (SHR), renal blood flow (RBF) has been reported to be very dependent on nitric oxide (NO); however, autoregulation is normal, albeit shifted to higher perfusion pressures. To test the hypothesis that in the SHR NO dependency of RBF autoregulation is diminished, we investigated RBF autoregulation in anesthetized young male SHR and normotensive Wistar-Kyoto (WKY) rats before and during acute intravenous NO synthase (NOS) inhibition with N(omega)-nitro-L-arginine (L-NNA) and urinary excretion of nitrate plus nitrite (U(NOx)V) at different renal perfusion pressures (RPP). Under baseline conditions, SHR had higher mean arterial pressure (147 +/- 4 mmHg) and renal vascular resistance (16 +/- 1 U) than WKY (105 +/- 4 mmHg and 10 +/- 0.5 U, respectively, P < 0.05). RBF was similar (9.4 +/- 0.5 vs. 10.3 +/- 0.1 ml x min(-1)x g kidney wt(-1)). Acute NOS blockade increased mean arterial pressure similarly, but there was significantly more reduction in RBF and hence an enhanced increase in renal vascular resistance in SHR (to 36 +/- 3 vs. 17 +/- 1 U in WKY, P < 0.001). The renal vasculature of SHR is thus strongly dependent on NO in maintaining basal RBF. The lower limit of autoregulation was higher in SHR than WKY in the baseline situation (85 +/- 3 vs. 71 +/- 2 mmHg, P < 0.05). Acute L-NNA administration did not decrease the lower limit in the SHR (to 81 +/- 3 mmHg, not significant) and decreased the lower limit to 63 +/- 2 mmHg (P < 0.05) in the WKY. The degree of compensation as a measure of autoregulatory efficiency attained at spontaneous perfusion pressures was comparable in SHR vs. WKY but with a shift of the curve toward higher perfusion pressures in SHR. Acute NOS blockade only increased the degree of compensation in WKY. Remarkably, U(NOx)V was significantly lower at spontaneous RPP in SHR. After reduction of RPP, the observed decrease in U(NOx)V was significantly more pronounced in WKY than in SHR. In conclusion, the renal circulation in SHR is dependent on high levels of NO; however, the capacity to modulate NO in response to RPP-induced changes in shear stress seems to be limited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Kidney / blood supply*
  • Kidney / metabolism*
  • Male
  • Nitrates / urine
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitrites / urine
  • Nitroarginine / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Renal Circulation / physiology*

Substances

  • Nitrates
  • Nitrites
  • Nitroarginine
  • Nitric Oxide
  • Nitric Oxide Synthase