Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats

Robin A. Felder, Mouin G. Seikaly, Peter Cody, Gilbert M. Eisner, Pedro A. Jose

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

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 angonist 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-2390 (n = 5). Intrarenal arterial infusion of the dopamine-1 agonist SKF-38393 did not affect glomerular filtration rate 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 hypertension rats is in part due to decreased response distal to the dopamine-1 receptor.

Original languageEnglish (US)
Pages (from-to)560-569
Number of pages10
JournalHypertension
Volume15
Issue number6 I
DOIs
StatePublished - 1990

Keywords

  • dopamine
  • dopamine receptors
  • essential hypertension
  • renal function
  • spontaneously hypertensive rats

ASJC Scopus subject areas

  • Internal Medicine

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