Tonic nociceptinergic inputs to neurons in the hypothalamic paraventricular nucleus contribute to sympathetic vasomotor tone and water and electrolyte homeostasis in conscious rats.
Central administration of nociceptin/orphanin FQ (N/OFQ) produces bradycardia, hypotension, diuresis, and antinatriuresis in rats. Because N/OFQ peptide (NOP) receptors exist in the paraventricular nucleus (PVN) of the hypothalamus, we hypothesized that N/OFQ acts in the PVN to alter cardiovascular and renal function. To test this premise, N/OFQ (10 and 100 pmol) or artificial cerebrospinal fluid (vehicle) was microinjected into the right PVN of conscious, chronically instrumented rats infused i.v. with isotonic saline. After injection, N/OFQ, but not vehicle, dose-dependently decreased renal sympathetic nerve activity (RSNA) and increased urine flow rate. At 100 pmol, N/OFQ also decreased urinary sodium and potassium excretion and increased free water clearance. In separate groups, the diuretic response to N/OFQ injection into the PVN was blunted in chronic bilaterally renal denervated rats and abolished in intact rats continuously infused i.v. with [Arg(8)]vasopressin (60 fmol/kg/min). Finally, in other studies bilateral microinjection of the NOP receptor antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101; 300 pmol) into the PVN increased heart rate and RSNA and decreased urine flow rate without altering electrolyte excretion. Pretreatment of separate rats with UFP-101 (300 pmol, PVN) blocked the N/OFQ-evoked (100 pmol) cardiovascular, renal sympathetic nerve, and renal excretory responses. Together, these findings demonstrate that in conscious rats activation of NOP receptors in the PVN by N/OFQ produces bradycardia, renal sympathoinhibition, and water diuresis. Moreover, UFP-101 blocks a tonically active inhibitory influence of endogenous N/OFQ on central sympathetic outflow and vasopressin pathways which arise from the PVN to affect heart rate and urine output.
Krowicki
Zbigniew K
ZK
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, USA. zkrowi@hotmail.com
Kapusta
Daniel R
DR
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000294:innervation; D003243:Consciousness; D004573:Electrolytes / Q000652:urine*; D006706:Homeostasis / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine / Q000737:chemistry; D014563:Urodynamics / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D004573:Electrolytes; D018847:Opioid Peptides; D010446:Peptide Fragments; C466980:nociceptin orphanin FQ(1-17)OH