The Effects of Long Term Oral Treatment with Indapamide on the Development of Doca-salt Hypertension in Rats : Vascular Reactivity Studies

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Abstract
The onset of DOCA[deoxycorticosterone acetate]-salt hypertension in male Sprague-Dawley rats was prevented during 11 wk of oral treatment with indapamide (0.5 or 10.0 mg/kg) or propranolol (60 mg/kg) administered in the diet. The body weights of the indapamide treated groups were significantly (P < 0.01) greater at weeks 4, 5, 6, 7 and 11, while the body weights and food intake of the propranolol treated group were significantly (P < 0.05) lower at week 11 than the control group. A significant reduction in heart wet weight (P < 0.001) was measured in the indapamide treated animals only. No significant diuresis nor natriuresis was measured in any group during week 11 of treatment. When all groups were subjected to an increased salt load, 4 wk after cessation of drug treatment only the indapamide (10 mg/kg) treated animals failed to show an increased blood pressure. Vascular reactivity studies carried out 6 wk after termination of drug treatment, indicated a significant (P < 0.01) reduction is pressor activity elicited by electrical stimulation of the entire sympathetic outflow in indapamide (10 mg/kg) treated pithed rats. No significant difference in the pressor activity elicited by noradrenaline [norepinephrine] (5 .times. 10-8-5 .times. 10-6 g/kg, i.v.) or tyramine (10-5-5 .times. 10-5 g/kg i.v.) was observed in any treatment group. Chronic oral treatment with indapamide or propranolol, prevented the onset of DOCA-salt hypertension in rats. A long lasting antihypertensive action of indapamide involving the sympathetic nervous system is also indicated.