Participation of multiple neurohumoral mechanisms in the antinatriuretic response to central MU opioids

V. A. Kenigs, S. F. Sezen, D. R. Kapusta

Research output: Contribution to journalArticlepeer-review

Abstract

Intracerebroventricular (i.c.v.) injection of the mu-opioid agonist, dermorphin (DER), produces an antinatriuretic response in conscious rats which is abolished by concurrent bilateral renal denervation (RDNX) and adrenalectomy. We tested the hypothesis that DER acts via these pathways to activate angiotensin II mechanisms and contribute to the antinatriuresis. Sprague-Dawley rats were instrumented with femoral arterial and venous catheters and a bladder cannula for collection of urine. During continuous i.v. infusion of isotonic saline (55 μl/min), changes in urine flow rate (V) and urinary sodium excretion (UNaV) were measured during control (C, 20 min) and during six consecutive periods (t20-t70, 10 min ea) starting 10 min after i.c.v. DER (0.1 nmol/kg). The role of angiotensin II in these renal responses was examined by repeating these studies in rats pretreated with the converting enzyme inhibitor, losartan (L,10 mg/kg; n=12) or vehicle (n=6). Rssults: In vehicle treated rats, i.c.v. DER produced a significant and sustained decrease in UNaV (C, 3.1±0.3 μeq/min/gkw vs DER t20, 0.8±0.1; t40, 0.8±0.2; t70, 1.8±0.3). In rats pretreated with losartan, i.c.v. DER produced a similar magnitude and time course antinatriuresis (C, 3.4±0.4 μeq/min/gkw; L, 4.5±0.4 vrs DER t20, 0.8±0.2; t40, 0.9±0.2; and 170, 1.8±0.3). In other studies, pretreatment of LOS did not prevent the antinatriuresis to i.c.v. dermorphin in rats having undergone chronic bilateral RDNX. While DER appears to activate multiple neurohumoral mechanisms to affect renal function, these results suggest that central mu opioids do not require angiotensin II to evoke an antinatriuretic response.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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