Functional evidence for increased nitric oxide involvement in cardiovascular and autonomic modulation by the PVN in conscious HU rats

Abstract

PVN is a pivotal hypothalamic integrative center for circulatory control and may play a role in autonomic regulation after cardiovascular deconditioning. Previous work demonstrates that neuronal nitric oxide (NO) synthase activity and protein expression is increased in the PVN of hindlimb unloaded (HU) rats, an animal model of cardiovascular deconditioning, compared to control. However, the functional role of increased nNOS is unknown. In this study we tested the hypothesis that tonic effects of NO in the PVN are augmented in HU rats. We studied the cardiovascular and autonomic responses to NOS inhibition in the PVN after return of HU rats to upright posture. Rats underwent 14 days HU or cage control (CC). Guide cannulas to the PVN were implanted on Day 9. Artery and vein catheters and renal nerve electrodes were implanted on Day 13 to record mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Baseline MAP was similar but resting HR was increased in conscious HU compared to control. Inhibition of NOS with L‐NMMA (2mM/100nL) into the PVN produced greater increases in MAP (CC: 13±1 vs. HU: 20±2 mmHg) and RSNA (CC: 155±34 vs. HU: 309±49% Baseline) in HU compared to control. Changes in HR to L‐NMMA were similar between groups. Data indicate that tonic NO function in the PVN is enhanced after HU in conscious rats and it may be part of the adjustments required for microgravity environment. HL55306