Benzamil blockade of brain Na+ channels averts Na(+)-induced hypertension in rats.

Abstract

To determine the possible involvement of brain amiloride-sensitive Na+ channels in Na(+)-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+ channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na(+)-induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol.kg-1.day-1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+ receptors in the brain and to be involved in the pressor mechanism of Na(+)-induced hypertension.

• Authors: M Nishimura, K Ohtsuka, A Nanbu, H Takahashi, M Yoshimura
• Journal: The American journal of physiology (Am J Physiol) Vol. 274 Issue 3 Pg. R635-44 (03 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9530228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Saline Solution, Hypertonic
• Sodium Channel Blockers
• benzamil
• Arginine Vasopressin
• Amiloride

Topics

• Amiloride (analogs & derivatives, pharmacology)
• Animals
• Arginine Vasopressin (urine)
• Blood Pressure (drug effects)
• Endothelin-1 (pharmacology)
• Heart Rate
• Hypertension (prevention & control)
• Injections, Intraventricular
• Male
• Natriuresis
• Rats
• Rats, Wistar
• Saline Solution, Hypertonic (pharmacology)
• Sodium Channel Blockers