Central kappa opioid receptor (KOR) activation produces a marked increase in renal sympathetic nerve activity with a concurrent free water diuresis in conscious rats. However, the role of KOR in the angiotensin II high salt diet (AngII) mediated hypertension model is yet to be determined. This study examines cFOS expression in several brain regions of AngII rats as compared to normal rats. In addition, cFos expression in these brain regions was examined following intracerebroventricular (ICV) microinjection of norbinaltorphimine (Nor‐BNI; 1 μg/5μl), a selective KOR antagonist. Alternate sets of forebrain sections were processed for c‐Fos using a commercially available antibody. Sections were also double labeled with vasopressin to anatomically define specific brain regions. Fos expression was significantly increased in several lamina terminalis and hypothalamic sites. ICV nor‐BNI produced significant decreases in cFos staining in the PVN (AngII, 106 ± 12; nor‐BNI 62 ± 7; P < .01) and OVLT (AngII, 132 ± 7; nor‐BNI 73 ± 5; P < .05). There was no significant change in urine and sodium excretion in all groups. Altogether, this data provides new information concerning the role of KOR in the regulation of blood pressure Grant Funding Source: 5SC2HL104639‐03

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

Intracerebroventricular (ICV) administration of the opioid‐like peptide, nociceptin/Orphanin (N/OFQ), produces a free water diuresis, in addition to marked effects on cardiovascular function and renal sympathetic nerve activity (RSNA). The present study utilized an angiotensin II high salt diet (ANGII) hypertension model to determine the central‐mediated cardiovascular effects of N/OFQ in anesthetized rats. Rats were chronically instrumented with cannulas in the femoral artery, femoral vein and urinary bladder and implanted with a renal nerve electrode. Cardiovascular and renal parameters were measured during control (C, two 10‐minutes) and for 60 minutes after ICV injection of saline vehicle or N/OFQ (10 mg/5 ml) in normotensive or ANGII rats. ICV N/OFQ produced a marked decrease in heart rate (HR), mean arterial pressure (MAP) and RSNA in both normotensive and ANGII rats. However, N/OFQ produced greater percentage decreases in HR, MAP and RSNA in ANGII rats than normotensive rats. N/OFQ also produced a significant increase in urine flow rate (V) in both groups, but ANGII blunted this diuretic effect. ICV saline did not produce any significant changes in any of the measured parameters. These findings suggest that, in urethane‐alpha‐chloralose anesthetized rats, N/OFQ appears to have greater effect on the cardiovascular system than on the renal. As such, drugs targeting the central N/OFQ receptors could facilitate the lowering of blood pressure in diseases, such as salt‐sensitive hypertension. Supported by NIH 5SC2 HL104639