EFFECT OF A NEW MINERALOCORTICOID ANTAGONIST MESPIRENONE ON ALDOSTERONE-INDUCED HYPERTENSION

The effects of the mineralocorticoid antagonist mespirenone on the development and maintenance of aldosterone-induced hypertension in Sprague-Dawley rats has been studied. Uninephrectomized saline-drinking male Sprague-Dawley rats were injected with either 0.2 ml olive oil, 50 g aldosterone, 1 mg mespirenone, 50 g aldosterone plus 500 g mespirenone, or 50 g aldosterone plus 1 mg mespirenone, each dissolved in 0.2 ml olive oil. Administration of aldosterone alone significantly increased the systolic blood pressure (SBP) from a control value of 114 +/- 3.6 to 162 +/- 4 mmHg by the end of the 3-wk experimental period. Mespirenone given alone had no effect on SBP. However, mespirenone given in combination with aldosterone reversed the hypertension caused by aldosterone in a dose-dependent manner. Saline consumption and urinary output were slightly increased in aldosterone-treated rats compared with the other groups, but the body and organ weights were comparable in all groups. Microscopic examination of kidney and heart showed no abnormalities due to mespirenone. These results suggest that in vivo administration of mespirenone to Sprague-Dawley rats effectively prevents the aldosterone-induced hypertension.