The neurogenic phase of angiotensin II–salt hypertension is prevented by chronic intracerebroventricular administration of benzamil

Hypertension induced by chronic administration of angiotensin II (AngII) is exacerbated by high‐salt intake. Previous studies have demonstrated that this salt‐sensitive component is due to increased activity of the sympathetic nervous system, suggesting an interaction of plasma AngII with sodium‐sensitive regions of the brain. This study tested the hypothesis that the salt‐sensitive component of AngII‐induced hypertension would be prevented by intracerebroventricular (ICV) administration of the sodium channel/transporter blocker benzamil. Male Sprague Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio telemetry and for ICV administration of benzamil or vehicle and placed in metabolic cages for measurement of sodium and water intake and excretion. In rats consuming a high‐salt diet (2.0% NaCl) and treated with ICV vehicle, administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30 mmHg. ICV administration of benzamil (16 nmol/day) had no effect during the first 5 days of AngII, but returned MAP to control levels by Day 13. There were minimal or no differences between ICV vehicle or benzamil groups in regards to sodium and water balance. A lower dose of ICV benzamil administered ICV at 8 nmol/day had no effect on the MAP response to AngII in rats on a high‐salt diet. Finally, in contrast to rats on a high‐salt diet, AngII had negligible effects on MAP in rats consuming a low‐salt diet (0.1% NaCl) and there were no differences in any variable between ICV benzamil (16 nmol/day) and ICV vehicle‐treated groups. We conclude that the salt‐sensitive component of AngII‐induced hypertension is dependent on benzamil blockable sodium channels or transporters in the brain.