Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats

Abstract

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.