Effect of central amiloride infusion on mineralocorticoid hypertension.
There is strong evidence from different types of studies, including the discrete infusion of agonists and antagonists and ablation of specific brain areas or transmitter-type neurons, that mineralocorticoids, in excess, act in the brain to elevate blood pressure. Aldosterone enhances the entry of Na+ through amiloride-sensitive Na+ channels in some mineralocorticoid-sensitive transport epithelial cells. To define possible cellular mechanisms involved in central mineralocorticoid action, benzamil, an amiloride analogue with selective affinity for the Na+ channel, was continuously infused intracerebroventricularly in three mineralocorticoid-dependent hypertension models in Sprague-Dawley rats, the continuous subcutaneous infusion of aldosterone, the intracerebroventricular infusion of aldosterone, and the ingestion of carbenoxolone, a synthetic licorice analogue. The intracerebroventricular infusion of 0.3 and 0.5 micrograms/h of benzamil, doses that did not have an adverse effect on growth and that had no effect on the blood pressure when infused subcutaneously, prevented the increase in blood pressure in these models. The infusion of these levels of benzamil had no effect on urine volume even in those animals in which it prevented an increase in blood pressure. These data suggest that the central effects of mineralocorticoids on blood pressure are mediated, at least in part, by the effects of mineralocorticoids on amiloride-sensitive sodium transport.
Gomez-Sanchez
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EP
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri.
Gomez-Sanchez
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CE
D000450:Aldosterone / Q000008:administration & dosage; D000584:Amiloride / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002229:Carbenoxolone / Q000008:administration & dosage; D004032:Diet; D006973:Hypertension / Q000139:chemically induced*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D008901:Mineralocorticoids; D051381:Rats; D017207:Rats, Sprague-Dawley
D008901:Mineralocorticoids; C013407:benzamil; D000450:Aldosterone; D000584:Amiloride; D002229:Carbenoxolone