Differential cardiovascular and renal responses produced by microinjection of the {kappa}-opioid U-50488H [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) methane sulfonate] into subregions of the paraventricular nucleus

The Journal of Pharmacology and Experimental Therapeutics
Helmut B GottliebDaniel R Kapusta

Abstract

kappa-Opioids produce a centrally mediated diuresis, antinatriuresis, and renal sympathoexcitation in vivo; however, the specific brain sites mediating these responses are unknown. This study examined the role of the hypothalamic paraventricular nucleus (PVN) and the renal sympathetic nerves in mediating the cardiovascular and renal responses to central kappa-opioid receptor activation. In ketamine/xylazine-anesthetized rats, bilateral microinjection of the selective kappa-agonist U-50488H [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) methane sulfonate; 100 ng] into the posterior magnocellular division of the PVN significantly increased urine flow rate (control, 47 +/- 9 microl/min; 40 min, 108 +/- 10 microl/min) without changing urinary sodium excretion or cardiovascular function. In other animals, microinjection of U-50488H into the same site elicited a similar water diuresis without a change in renal sympathetic nerve activity. In contrast, microinjection of U-50488H (100 ng) into the parvocellular PVN produced an immediate pressor response (Delta 16 +/- 3 mm Hg) that occurred with a potential baroreflex evoked bradycardia (Delta -26 +/- 8 beats per minute), renal sympathoinhibition (Delta...Continue Reading

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Citations

Dec 14, 2005·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Grace P ChenJames H Caldwell
Sep 29, 2007·Canadian Journal of Physiology and Pharmacology·Wei Qi, Francine G Smith
Aug 25, 2007·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Assaf T GordonAllen Lebovits
May 5, 2011·European Journal of Pharmacology·Matthew F PetersTodd A Brugel
Sep 16, 2006·Peptides·Richard J Bodnar, Gad E Klein
May 27, 2006·Experimental Physiology·Wei Qi, Francine G Smith
Jun 25, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Helmut B Gottlieb, Daniel R Kapusta

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