title: Chronic high-NaCl intake prolongs the cardiorenal responses to central N/OFQ and produces regional changes in the endogenous brain NOP receptor system.
abstract: Intracerebroventricular nociceptin/orphanin FQ (N/OFQ) produces cardiovascular depressor, diuretic, and renal sympathoinhibitory responses in conscious rats. These studies examined how a chronic high-NaCl intake alters these peptide-evoked responses and the activity of the endogenous central N/OFQ peptide (NOP) receptor system. In normotensive Sprague-Dawley rats fed a chronic (3-wk) high (8%)-NaCl diet, intracerebroventricular N/OFQ (5.5 nmol) produced prolonged bradycardic, hypotensive, and diuretic responses but failed to suppress renal sympathetic nerve activity. In a separate group of rats maintained on a high-NaCl diet, intracerebroventricular infusion of the NOP receptor antagonist UFP-101 significantly decreased urine output. At the tissue level, high-NaCl treatment of rats significantly increased NOP receptor density, without altering endogenous N/OFQ peptide levels in whole hypothalamus (control, 712 +/- 35 fmol/mg vs. 8% NaCl, 883 +/- 49 fmol/mg, P < 0.05) and paraventricular nucleus. Furthermore, in the hypothalamus, basal GTPgammaS binding was increased without altering the sensitivity of N/OFQ-stimulated G protein coupling. In contrast, in whole medulla and the ventrolateral medulla (VLM), high-NaCl treatment decreased NOP receptor density (medulla: control, 1,473 +/- 131 fmol/mg vs. 8% NaCl, 327 +/- 31 fmol/mg, P < 0.05) and endogenous N/OFQ peptide levels (medulla: control, 35.3 +/- 2 fmol/mg vs. 8% NaCl, 11.9 +/- 3 fmol/mg, P < 0.05), while increasing the sensitivity of G protein signaling pathways to N/OFQ stimulation. Together, these findings suggest that during a chronic high-salt intake, regional changes in the activity of the N/OFQ-NOP system in the brain may contribute to the tonic regulation of cardiovascular function and urine output and to the altered physiological responses to exogenous central N/OFQ.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA. rwainf@lsuhsc.edu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Wainford
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kapusta
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure; D002319:Cardiovascular System / Q000294:innervation*; D004231:Diuresis; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006339:Heart Rate; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014563:Urodynamics; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D001127:Arginine Vasopressin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018847:Opioid Peptides; D011957:Receptors, Opioid; D017673:Sodium Chloride, Dietary; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722285:Oprl1 protein, rat