The Cardiovascular Effects Produced by Intracerebroventricular Microinjection of N/OFQ in Angiotensin II/High Salt Diet Rats.

Abstract

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