Central mineralocorticoid receptor antagonism blocks hypertension in Dahl S/JR rats.
The development of hypertension in the S/JR rat is accelerated and exacerbated by a high salt consumption. It has been reported that the intracerebroventricular infusion of RU28318, a selective mineralocorticoid antagonist, at doses that are ineffective when administered subcutaneously, inhibits the development of the hypertension produced by the subcutaneous infusion of aldosterone or deoxycorticosterone in normotensive rats. RU28318 was continuously infused intracerebroventricularly or subcutaneously in Dahl S/JR rats before or after the onset of hypertension induced by a high-salt diet. The centrally infused mineralocorticoid antagonist inhibited the initiation of the increase in blood pressure, when the infusion was started concomitantly with the high-salt diet, and blocked its further increase in rats whose blood pressure had already become significantly elevated with 2 wk of a high-salt diet. The subcutaneously infused mineralocorticoid antagonist had no effect. These data serve to strengthen the hypothesis that the mineralocorticoid receptor in the brain is crucial to the genesis of certain forms of hypertension.
Gomez-Sanchez
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EP
Research Division, James A. Haley Veterans Hospital, Tampa, Florida.
Fort
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C
Thwaites
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004032:Diet; D005260:Female; D006973:Hypertension / Q000517:prevention & control*; D007276:Injections, Intraventricular; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013148:Spironolactone; D012965:Sodium Chloride; C041006:RU 28318