Intracerebroventricular Infusion of Aldosterone Induces Hypertension in Rats*

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Abstract
There is suggestive evidence for the direct participation of mineralocorticoids in the production of centrally mediated hypertension. Unilaterally nephrectomized Sprague-Dawley rats received a continuous infusion for 30 days using implanted osmotic minipumps with (1) artificial spinal fluid (CSF) intracerebroventricularly (icvt); (2) 0.005 .mu.g aldosterone/h icvt; (3) 0.005 .mu.g aldosterone/h sc; (4) 0.5 .mu.g aldosterone/h sc. There was no significant difference between the groups in average weight gain (52 .+-. 2 g) or organ weight to body weight, nor was urine volume increased above normal except in the group receiving the high sc dose of aldosterone. Blood pressure was significantly elevated only in those animals receiving 0.005 .mu.g aldosterone/h icvt and 0.5 .mu.g aldosterone/h sc. A second experiment was done using a specific spironolactone-type mineralocorticoid antagonist, prorenone. The rats were grouped as follows: (1) CSF icvt; (2) 0.005 .mu.g/h aldosterone icvt; (3) 0.005 .mu.g/h aldosterone plus 0.005 .mu.g/h prorenone icvt; (4) 0.005 .mu.g/h aldosterone plus 0.02 .mu.g/h prorenone icvt; (5) 0.02 .mu.g/h prorenone icvt. This study confirmed that this minute dose of aldosterone infused icvt produced a statistically significant increase in blood pressure with no increase in urine volume. Both the low, 0.005 .mu.g/h, and high 0.02 .mu.g/h, doses of prorenone antagonized the pressor effect of aldosterone when infused with aldosterone into the lateral cerebral ventricle. The groups receiving 0.02 .mu.g/h prorenone icvt or CSF icvt did not differ significantly in those parameters measured. A dose of aldosterone that was too small to produce changes in blood pressure when infused systemically was found to produce hypertension without polydypsia/polyuria when infused intrathecally. This pressor effect could be blocked by the concomitant infusion of a specific antagonist, prorenone. The study presented offers strong circumstantial evidence supporting a direct hypertensinogenic effect of aldosterone within the central nervous system.