Intracerebroventricular (ICV) benzamil attenuates the maintenance phase of DOCA-salt hypertension: Role of the paraventricular nucleus of the hypothalamus.

The present study was conducted to characterize the effect of ICV benzamil on the time course of DOCA-salt hypertension and the role of the paraventricular nucleus (PVN) in these responses. Uninephrectomized rats were instrumented with a cannula connected to a minipump for infusion of benzamil (BENZ; N=6, 20 nmol/day) or vehicle (VEH; N=6), as well as a transmitter for continuous recording of arterial pressure (AP). DOCA (50 mg) was implanted subcutaneously and AP was recorded for 5 days while rats drank water. Baseline AP was similar (∼100 mmHg) in both groups. Water was replaced with saline and AP recorded for 20 more days. During the first week of saline, group responses were indistinguishable. Starting on Day 7 of saline, marginal group differences in AP emerged. By Day 14, consistent differences emerged, with AP increasing to a greater extent in VEH (∼130 mmHg) than BENZ (∼115 mmHg; p<0.05). On Day 20, AP remained higher in VEH (∼135 mmHg) as compared to BENZ (∼120 mmHg; p <0.01). Brains were then harvested and processed for c-Fos immunohistochemistry in the PVN as an indicator of neuronal activity. Initial results suggest that BENZ reduced PVN c-Fos expression in DOCA-salt rats. We conclude that BENZ treatment attenuates the maintenance phase of DOCA-salt hypertension and that this may be a result of reduced neuronal activity in CNS pressure-regulatory regions, including the PVN. HL 064178 [ABSTRACT FROM AUTHOR]