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 Citations (Scopus)

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 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 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 hypertensive 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 PART 1
StatePublished - Jun 1990

Fingerprint

Dopamine Agents
Dopamine Antagonists
Inbred SHR Rats
Kidney
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Dopamine Agonists
Dopamine Receptors
Sodium
Inbred WKY Rats
Glomerular Filtration Rate
Natriuretic Agents
Natriuresis
Diuresis
Pentobarbital
Autoradiography
Dopamine
Anesthesia
SCH 23390

Keywords

  • Dopamine
  • Dopamine receptors
  • Essential hypertension
  • Renal function
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Felder, R. A., Seikaly, M. G., Cody, P., Eisner, G. M., & Jose, P. A. (1990). Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. Hypertension, 15(6 PART 1), 560-569.

Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. / Felder, Robin A.; Seikaly, Mouin G.; Cody, Peter; Eisner, Gilbert M.; Jose, Pedro A.

In: Hypertension, Vol. 15, No. 6 PART 1, 06.1990, p. 560-569.

Research output: Contribution to journalArticle

Felder, RA, Seikaly, MG, Cody, P, Eisner, GM & Jose, PA 1990, 'Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats', Hypertension, vol. 15, no. 6 PART 1, pp. 560-569.
Felder RA, Seikaly MG, Cody P, Eisner GM, Jose PA. Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. Hypertension. 1990 Jun;15(6 PART 1):560-569.
Felder, Robin A. ; Seikaly, Mouin G. ; Cody, Peter ; Eisner, Gilbert M. ; Jose, Pedro A. / Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. In: Hypertension. 1990 ; Vol. 15, No. 6 PART 1. pp. 560-569.
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