Effect of intracerebroventricular (ICV) and subcutaneous (SC) benzmail administration on AngII‐salt hypertension

AngII‐salt hypertension in the rat is mediated, in part, by activation of the sympathetic nervous system. In the present study we tested the hypothesis that benzamil (Benz) blockable sodium channels and transporters in the brain contribute to this salt‐sensitive model. Male Sprague Dawley rats consuming a high salt diet (2.0% NaCl) were instrumented with telemeters to measure mean arterial pressure (MAP), ICV cannulae for continuous Benz or vehicle infusion, and placed on one of 6 treatments for the duration of the protocol; Benz‐ICV (4 or 8 nmol/day), vehicle‐ICV (Veh‐ICV; 2 groups), or Benz‐SC (4 or 8 nmol/day). MAP was monitored for 3 days, then AngII was administered (150 ng/kg/min, sc) for 14 days. There were no differences in MAP between the six groups prior to AngII. MAP increased ~30 mmHg in both Veh‐ICV groups by Day 14 of AngII. At the low dose, neither Benz‐ICV, nor Benz‐SC, affected the hypertensive response to AngII. In contrast, AngII‐salt hypertension was abolished by Benz‐ICV at the higher dose. Benz‐SC at the higher dose attenuated AngII‐salt hypertension by 50%. We conclude that benzamil‐sensitive sodium channels/transporters in the brain contribute to AngII‐salt hypertension in the rat.