Effects of cerebroventricular administration of ouabain on renal hemodynamics in anesthetized dogs: evidence for the participation of renal dopaminergic vasodilator fibers

GJ Hom and BS Jandhyala

Cerebroventricular infusion of ouabain (10(-6) M) in cerebrospinal fluid produced significant increases in renal blood flow and reductions in renal vascular resistance in chloralose anesthetized, vagotomized dogs; these renal effects were not accompanied by any changes in arterial blood pressure and heart rate. Infusion of a higher concentration of ouabain (10(-5) M) enhanced significantly blood pressure, heart rate, renal vascular resistance and reduced renal blood flow. The renal vasodilator effects precipitated by lower concentration of ouabain have not been documented before and the mechanisms involved in these observations were investigated in the present study. Pretreatment of the dogs with indomethacin did not prevent renal vasodilator effects of ouabain, indicating that prostaglandins were not involved. Acute renal denervation abolished these actions suggesting that these renal vascular effects were mediated neurogenically. In the dogs, pretreated with i.v. sulpiride, a dopamine receptor antagonist, central infusions of ouabain (10(-6) M) produced significant increases in blood pressure, renal vascular resistance and reduced renal blood flow. These effects were opposite to those noted in control animals. These data suggested that vasodilatation induced by central ouabain was mediated via activation of renal dopaminergic fibers. Prior intraventricular infusion of small doses of sulpiride that antagonized central dopamine receptors, without affecting peripheral sites, also prevented but did not reverse the renal effects of ouabain. Selective blockade of central alpha receptors with phentolamine also abolished ouabain-induced renal vasodilatation. In addition, after central alpha receptor blockade ouabain increased arterial blood pressure. In the dogs pretreated with i.v. phentolamine, cerebroventricular ouabain did not produce any changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 230, Issue 2, pp. 275-283, 08/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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