Plasma catecholamines, noradrenaline metabolism and vascular response in desoxycorticosterone acetate hypertension of rats

Abstract

Mineralocorticoid hypertension was induced in male Wistar rats by the injection of desoxycorticosterone acetate (DOCA) in oily solution (2 X 5 mg/kg daily for 7 days) and of desoxycorticosterone trimethylacetate in a microcrystalline suspension (15 mg/kg every third day for 4 weeks). A 1% NaCl solution or demineralized water was given as drinking fluid. Four weeks after the beginning of treatment, mean arterial blood pressure was 161 +/- 3.8 mmHg in DOCA-saline treated and 140 +/- 5.9 mmHg in DOCA-water-treated rats. Basal plasma levels of noradrenaline and adrenaline did not differ in conscious, unrestrained DOCA-treated rats and in control rats 3, 7 and 28 days after the beginning of hormone administration. Furosemide (50 mg/kg) caused within 30 min the same degree of diuresis and natriuresis in DOCA-treated and in control rats, but the plasma noradrenaline concentration in DOCA-treated rats rose to a higher level than in the controls. The isolated perfused hearts of rats which received DOCA for 7 and 28 days, respectively, had a reduced uptake of [3H]noradrenaline as compared to the controls. In isolated perfused hindlimb preparations from rats which had received DOCA for 7 days, the dose-response curve to noradrenaline but not that to KCl was shifted to the left. However, when DOCA and saline were given for 28 days, besides a higher sensitivity to noradrenaline an increased maximum response was observed with both noradrenaline and KCl. It is concluded that adrenergic tone is enhanced during the development of DOCA hypertension. Since the changes in the sympathetic nervous system in DOCA-water-treated rats, which had a less pronounced hypertension, were similar to those in DOCA-NaCl-treated rats, alterations in adrenergic vascular tone were not directly related to the level of the blood pressure.