Renal response to methoxamine in portal hypertensive rats: role of prostaglandins and nitric oxide

J Hepatol. 1996 Aug;25(2):206-11. doi: 10.1016/s0168-8278(96)80075-4.

Abstract

Background/aims: In the present study we have evaluated the role of nitric oxide and prostaglandins in the renal vascular response to a vasoconstrictor (methoxamine) and to endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators.

Methods: The experiments were performed in isolated and perfused kidneys of portal vein ligated and sham rats under various treatments.

Results: Baseline renal perfusion pressure was lower in the portal vein ligated than in the sham group (37.2 +/- 2.6 vs 48.4 +/- 2.5 mmHg). Indomethacin (10(-5)M) did not modify baseline renal perfusion pressure in any group, but the nitric oxide inhibitor N(W)-Nitro-L-Arginine (10(-4) M) increased it in both sham and portal vein ligated kidneys, but without abolishing the differences between them. The vasoconstrictor renal response to methoxamine was blunted in portal vein ligated rats compared to controls. Indomethacin did not modify this renal hyporesponsiveness, but N(W)-Nitro-L-Arginine completely abolished it. In another set of experiments, both acetylcholine and nitroprusside caused dose-dependent vasodilation in kidneys, preconstricted with methoxamine, from sham and portal vein ligated rats, and there were no significant differences between them. N(W)-Nitro-L-Arginine reduced acetylcholine-induced vasodilation and did not modify the vasodilation evoked by nitroprusside.

Conclusions: These results indicate that the renal vasculature of portal vein ligated rats shows a basal reduction in perfusion resistance that is not related to nitric oxide or prostaglandins. However, increased nitric oxide production interferes with the effects of the alfa-agonist methoxamine. This suggests that nitric oxide plays an important role in the modulation of the renal vascular responses to vasoconstrictors in portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Enzyme Inhibitors / pharmacology
  • Hypertension, Portal / physiopathology*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Male
  • Methoxamine / pharmacology*
  • Nitric Oxide / physiology*
  • Nitroarginine / pharmacology
  • Nitroprusside / pharmacology
  • Perfusion
  • Prostaglandins / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects
  • Vasoconstriction
  • Vasodilator Agents / pharmacology

Substances

  • Enzyme Inhibitors
  • Prostaglandins
  • Vasodilator Agents
  • Nitroprusside
  • Nitroarginine
  • Nitric Oxide
  • Methoxamine
  • Acetylcholine
  • Indomethacin