Identification of CNS Sites Involved in the Cardiovascular and Renal Responses Elicited by Nociceptin/Orphanin FQ in Conscious Hypertensive Rats via c‐Fos Immunocytochemistry.

Abstract

Intracerebroventricular (ICV) administration of the opioid‐like peptide agonist, nociceptin/Orphanin FQ (N/OFQ), produces a free water diuresis in addition to marked depressor effects on cardiovascular function and renal sympathetic nerve activity (RSNA). This study examined the changes in cFos expression in forebrain regions of angiotensin II high salt diet (ANGII) hypertensive rats following ICV administration of N/OFQ or saline vehicle. Protocol: 14 days prior to the experiment day, rats were implanted with an osmotic pump filled with angiotensin II and placed on a 2% high salt diet. At the day of the experiments, animals were placed in a metabolic cage and allowed to habituate for 3 hours. Following habituation, then two 15 minutes control periods, rats were than microinjected with either saline vehicle or nociceptin. Ninety minutes after the ICV injection, animals were perfused. Alternate sets of forebrain sections were processed for cFos using a commercially available antibody (Oncogene AB‐5). Results: ANGII treatment significantly increased cFos staining in the magnocellular and parvocellular PVN, SON, PNZ, OVLT, MPA and DMH brain sites as compared to Sham rats. ICV N/OFQ produced significant decrease in c‐Fos staining in the magnocellular PVN, SON, PNZ, OVLT, MPA and DMH of ANGII rats as compared to ANGII group microinjected with saline vehicle. Together, central N/OFQ receptor activation in these forebrain regions may contribute directly to or indirectly participate in the neuropathways involved in the cardiovascular and renal effects of N/OFQ. Supported by NIH 5SC2 HL104639