Abstract
Studies were performed in conscious Sprague-Dawley rats to characterize the changes in renal excretory function produced by activation ofdelta opioid systems. The intravenous infusion of 50 μg/kg/min, BW373U86 (BW), a nonpeptide delta opioid receptor agonist, produced a significant increase in urine flow rate and urinary sodium excretion. The infusion of BW at a dose of 30 μg/kg/min produced diuresis without affecting urinary sodium excretion. In contrast, BW did not alter either renal excretory parameter at a dose of 10 μg/kg/min. The renal responses produced by BW occurred without changes in heart rate or mean arterial blood pressure. The diuretic and natriuretic responses produced by the i.v. infusion of BW (50 μg/kg/min) were prevented by pretreatment of animals with the selective delta opioid receptor antagonist, naltrindole (1 mg/kg, i.v.). When administered alone, naltrindole (1 mg/kg, i.v.) failed to change any systemic cardiovascular or renal excretory parameter. In other groups of animals, the peripheral administration of the deltaopioid receptor agonist, SNC80, also evoked a profound diuretic and natriuretic response (naltrindole sensitive) similar to that produced by BW. In contrast to these findings, the diuretic and natriuretic response produced by BW infusion (30 or 50 μg/kg/min, i.v.) was abolished in rats having undergone chronic bilateral renal denervation. Together, these results demonstrate that the peripheral administration of BW373U86 or SNC80 produce marked diuretic and natriuretic responses in conscious Sprague-Dawley rats via a delta opioid receptor pathway and that intact renal nerves are required for mediating these responses. Although endogenous deltaopioid systems do not appear to exert a tonic influence under basal conditions, these findings suggest that delta opioid pathways may evoke significant changes in renal excretory function under conditions in which these systems are activated.
Footnotes
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Send reprint requests to: Daniel R. Kapusta, Ph.D., Department of Pharmacology, LSU Medical Center, 1901 Perdido St., New Orleans, LA 70112.
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↵1 This work was supported by grants to D.R.K. from the National Institute of Diabetes and Digestive and Kidney Diseases (DK43337) and the American Heart Association, Louisiana Affiliate (91–6-08B).
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↵2 Present address: Sena F. Sezen, Ph.D., Brady Urological Institute, The Johns Hopkins Hospital, 600 N. Wolfe St., Marburg 414, Baltimore, MD 21287.
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↵3 Correspondence to Sena F. Sezen, Ph.D.
- Abbreviations:
- BW
- BW373U86, 4-[(α-R*)-α-[2S*, 5 R*)- 4 allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N, N-diethylbenzamide
- SNC80
- methyl ether of (+)BW373U86
- i.v. intravenous.
- Received December 29, 1997.
- Accepted May 26, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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