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

Hypertension induced by chronic administration of angiotensin II ( A ng II ) 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 A ng II with sodium‐sensitive regions of the brain. This study tested the hypothesis that the salt‐sensitive component of A ng II ‐induced hypertension would be prevented by intracerebroventricular ( ICV ) administration of the sodium channel/transporter blocker benzamil. Male S prague D awley 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 A ngII (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 A ng II , but returned MAP to control levels by D ay 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 A ng II in rats on a high‐salt diet. Finally, in contrast to rats on a high‐salt diet, A ng II 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 A ng II ‐induced hypertension is dependent on benzamil blockable sodium channels or transporters in the brain.