EFFECT OF CENTRAL INFUSION OF BENZAMIL ON DAHL-S RAT HYPERTENSION

The effect of continuous central infusion of benzamil, a Na+ channel-selective amiloride analogue, on the salt-induced hypertension in inbred Dahl salt-sensitive (SS/jr) rats was assessed. The continuous intracerebroventricular or subcutaneous infusion of benzamil at doses which have no effect when infused systemically was started at the same time or 2 wk after saline was substituted for drinking water, when the rats' blood pressures had become significantly elevated. Within 13 days, drinking saline caused a similar and significant increase in the blood pressures of rats receiving the vehicle intracerebroventricularly and 1 mu g/h of benzamil subcutaneously, which persisted throughout the 4-wk experiment. The intracerebroventricular infusion of 1 or 0.3 mu g/h benzamil, started at the same time the salt challenge was instituted, significantly deterred the increase in blood pressure over 4 wk. The intracerebroventricular, but not the subcutaneous, infusion of benzamil at 0.5 mu g/h arrested the increase in blood pressure in rats that were already hypertensive after 12 days on saline. Within 3 days the pressures in the intracerebroventricular and subcutaneous benzamil groups became significantly different, due to the further increase of the blood pressure in those animals receiving the intracerebroventricular vehicle with subcutaneous benzamil. There was no significant difference in weight gain throughout the experiment or in 24-h urine volumes and urinary Na+-to-K+ ratio at days 5 and 12 of benzamil infusion between groups. These data strongly suggest a centrally mediated component of the hypertension in the Dahl SS/jr rats, which can be mitigated by the chronic central infusion of a Na+-channel antagonist at a dose that does not alter urine volume, urinary Na+-to-K+ ratio, or body weight.