Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats

Hypertension. 1990 Jun;15(6 Pt 1):560-9. doi: 10.1161/01.hyp.15.6.560.


Activation of renal dopamine-1 receptors decreases sodium transport. However, the spontaneously hypertensive rat retains sodium despite increased renal dopamine concentration. We tested the hypothesis that the abnormal sodium handling in spontaneously hypertensive rats (Okamoto-Aoki strain) is related to a decreased dopaminergic response by studying the effects of the intrarenal infusion of the dopamine-1 agonist SKF-38393 and the dopamine-1 antagonist SCH-23390 in hypertensive and in normotensive Wistar-Kyoto rats. Rats (9-16 weeks old) were studied with renal nerves intact under pentobarbital anesthesia (n = 5-6 in each group). Specificity of dopamine-1 effects of SKF-38393 was verified because its natriuretic effect was blocked in a dose-related manner by the dopamine-1 antagonist SCH-23390 (n = 5). Intrarenal but resulted in a dose-related natriuresis and diuresis in normotensive but not in hypertensive rats. Intrarenal arterial infusion of the dopamine-1 antagonist SCH-23390 alone induced an antinatriuresis, without affecting glomerular filtration rate, in normotensive but not in hypertensive rats. Addition of the dopamine-2 antagonist YM-09151 to the dopamine-1 antagonist infusion did not enhance the effect of the dopamine-1 antagonist. The lack of response to the dopamine-1 agonist or antagonist in hypertensive rats was not due to differences in renal dopamine-1 receptor density (1.3 +/- 0.3 pmol/mg protein for spontaneously hypertensive rats, n = 4; 1 +/- 0.2 for Wistar-Kyoto rats, n = 4) or affinity; distribution determined by autoradiography was also similar. The abnormal renal sodium handling in 9-16-week-old spontaneously hypertensive rats is in part due to decreased response distal to the dopamine-1 receptor.

Publication types

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

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Benzamides / pharmacology
  • Benzazepines / pharmacology
  • Dopamine Agents / pharmacology*
  • Dopamine Antagonists
  • Hypertension / physiopathology*
  • Kidney / metabolism
  • Kidney / physiopathology*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Dopamine / analysis
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine D1
  • Regression Analysis
  • Urodynamics / drug effects


  • Benzamides
  • Benzazepines
  • Dopamine Agents
  • Dopamine Antagonists
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • nemonapride