Vascular and renal effects of dopamine during extracellular volume expansion: Role of nitric oxide pathway

Life Sci. 2006 Feb 28;78(14):1543-9. doi: 10.1016/j.lfs.2005.07.024. Epub 2005 Oct 11.

Abstract

Objective: The aim of the study was to determine the possible role of NO-system activation in vascular and renal effects of the dopaminergic system and the probable interaction between both systems during acute volume expansion in rats.

Design and methods: Expanded (10% bw) and non-expanded anaesthetized male Wistar rats were treated with haloperidol, a DA receptor antagonist (3 mg/kg bw, ip). Mean arterial pressure, diuresis, natriuresis, renal plasma flow, glomerular filtration rate, nitrites and nitrates excretion (NOx) were determined. NADPH diaphorase activity was measured using a histochemistry technique in kidney, aorta and renal arteries. NOS activity in kidney and aorta from expanded and non-expanded animals was determined with L-[U14C]-arginine substrate, in basal conditions and after DA (1 microM) administration.

Results: The hypotensive effect of L-arg and hypertension induced by L-NAME were not modified by haloperidol. This blocker reverted the increase in diuresis, natriuresis and RPF induced by L-arg in both groups. Dopaminergic blockade induced a decrease in NOx excretion and in NADPH-diaphorase activity in glomeruli, proximal tubule and medullar collecting duct and in endothelium and vascular smooth muscle of renal arteries. DA induced an increase in NOS activity in renal medulla and cortex in both groups, but no changes in the aorta were observed.

Conclusions: Our results suggest that renal DA would be associated with the renal response induced by NO during extracellular volume expansion. NO-system activation would be one of the mechanisms involved in renal DA activity during saline load, but NO appears not to be involved in DA vascular effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Citrulline / analysis
  • Diuresis / drug effects
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Extracellular Fluid / drug effects
  • Haloperidol / pharmacology
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • NADPH Dehydrogenase / analysis
  • NADPH Dehydrogenase / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Natriuresis / drug effects
  • Nitrates / metabolism
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Nitrites / metabolism
  • Rats
  • Rats, Wistar
  • Renal Artery / drug effects
  • Renal Artery / enzymology
  • Renal Plasma Flow* / drug effects

Substances

  • Dopamine Antagonists
  • Nitrates
  • Nitrites
  • Citrulline
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • NADPH Dehydrogenase
  • Haloperidol
  • NG-Nitroarginine Methyl Ester
  • Dopamine