Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension.
The chronic intracerebroventricular (icv) infusion of aldosterone in rats and dogs elevates the blood pressure within 10-14 days at doses far below those that produce hypertension systemically. The effect in rats is dose dependent and blocked by the concomitant icv infusion of the antimineralocorticoid, prorenone. The effect of the icv infusion of RU28318, another specific spironolactone mineralocorticoid antagonist, on the hypertension produced by chronic subcutaneous (sc) administration of aldosterone in sensitized rats was reported. Miniosmotic pumps were used to deliver 1 micrograms/h aldosterone sc and 1.1 micrograms/h RU8318 icv. Over a 24-day period the indirect systolic blood pressure of the control, RU28318 icv, and aldosterone sc plus RU28318 icv groups increased from 105 to 123 mmHg and were not significantly different from each other, whereas the aldosterone sc group increased to 156 mmHg. RU28318, icv or sc, did not alter the increase in urine volume produced by aldosterone sc, and there was no significant differences in weight between the groups. This study provides evidence of the importance of the central nervous system in the pathogenesis of hypertension produced by systemic mineralocorticoid excess.
Gómez-Sánchez
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EP
Research Service, J.A. Haley Veterans Administration Hospital, Tampa, Florida 33612.
Fort
C M
CM
Gómez-Sánchez
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CE
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007263:Infusions, Parenteral; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012982:Sodium, Dietary / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D012982:Sodium, Dietary; D013148:Spironolactone; D000450:Aldosterone; C041006:RU 28318