Dose–response studies of intracerebroventricular infusion of aldosterone in sensitized and non-sensitized rats


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Abstract

We have shown previously that the intracerebroventricular (icvt) infusion of 5 ng/h aldosterone (ALD) in the sensitized rat (one kidney removed, 1% NaCl plus 0.15% KCl solution to drink) produced hypertension similar in amplitude and time of onset to a 100-fold dose administered subcutaneously (s.c.), while a 5-ng/h subcutaneous infusion had no effect on blood pressure (BP). Dose–response studies on the icvt infusion of ALD were carried out in sensitized and non-sensitized (intact, with tap water to drink) male Sprague-Dawley rats (SDR). In both studies, a control group received the diluent, artificial cerebrospinal fluid (CSF), icvt. In sensitized rats, the pressures became significantly (P<0.05) elevated at day 7 in those receiving 15 ng/h icvt, day 11 in those receiving 5 ng/h icvt and 500 ng/h s.c. and day 18 in those receiving 1.5 ng/h icvt. The indirect systolic BPs at day 20 of infusion were 119 ± 0.8 (s.e.) mmHg for controls, 182 ± 5 for 15 ng/h icvt, 140 ± 2 mmHg for 5 ng/h icvt, 131 ± 1 mmHg for 1.5 ng/h icvt, 125 ± 1 mmHg for 0.5 ng/h, and 159 ± 5 mmHg for 500 ng/h s.c. Recovery (removal of pumps and return to water to drink) for 18 days resulted in the return of normal pressures in all groups except the 15 ng/h, icvt group in which pressures remained slightly, but significantly elevated at 127 ± 3 mmHg. In non-sensitized rats, the. pressures became significantly elevated in animals receiving 45 ng/h icvt and 1 µg/h s.c. by day 14. After 45 days of infusion, the pressures of these rats were 144 ± 2 and 141 ± 2 mmHg, respectively, while that of the controls and the non-sensitized rats on the lower icvt doses was 124 ± 5 mmHg. The 0.5-ng/h dose in the sensitized rats and the 5- and 15-ng/h doses in the non-sensitized rats had no significant effect on BP. The 24-h urine volumes in the sensitized rats receiving 15 ng/h icvt and 500 ng/h s.c. were significantly increased by day 14 and dropped to control levels by day 18 of the recovery period. There was no significant difference from control values in urine output in the sensitized rats receiving the lower doses of ALD icvt, or in any of the non-sensitized animals. Sensitization by decreasing renal mass and increasing Na intake was important but not necessary for this model

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