Chronic activation of central alpha(2)-adrenoceptors prevents hypertensionin DOCA-salt rats

The effects of chronic intracerebroventricular (i.c.v.) injections of the a lpha(2)-adrenoceptor agonist, xylazine, on blood pressure were examined in DOCA-salt rats. Acute studies also examined the renal sympathetic nerve act ivity (RSNA) and renal excretory responses produced by i.c.v. xylazine in r ats with established DOCA-salt hypertension. Rats implanted with a chronic i.c.v. cannula for drug injection were used. In chronic studies, four group s were investigated: control rats treated with s.c. soybean oil and i.c.v. saline; DOCA-salt rats (s.c. deoxycorticosterone acetate) receiving i.c.v. saline, xylazine or the alpha(2)-adrenoceptor antagonist, yohimbine. During vehicle or DOCA-salt treatment, xylazine (0.2 ng/mu g) or yohimbine (10 mu g/kg) was injected i.c.v. daily (three times). In DOCA-salt rats receiving i.c.v. saline, resting mean arterial pressure (MAP) was elevated on days 1 5 and 30 (135+/-5 and 160+/-6 mmHg, respectively). Chronic i.c.v. xylazine significantly attenuated the rise in MAP produced by DOCA-salt (day 15, 118 +/-5 mmHg; day 30, 121+/-4 mmHg). Alternatively, chronic i.c.v. yohimbine s hortened the onset (day 15, 152+/-7 mmHg) and augmented the hypertension in DOCA-salt rats (0 survival by day 30). In acute studies, i.c.v. xylazine e licited a profound natriuresis and diuresis as well as a reduction in RSNA without altering MAP. This study demonstrates that the ongoing (tonic) acti vity of central alpha(2)-adrenoceptor mechanisms are critically involved in regulating blood pressure in the DOCA-salt treated rat. In this manner, an enhanced activity of central alpha(2)-adrenoceptor systems acts to protect against a rise in blood pressure. In contrast, the attenuation of central alpha(2)-adrenoceptor stimulation evokes hypertension. The central action o f xylazine to prevent hypertension may be associated with the inhibition of sympathetic outflow to the kidneys and evokes an enhanced natriuresis. By inhibiting the avid sodium retention elicited by DOCA-salt treatment, the c entral activation of alpha(2)-adrenoceptors delays the onset and the severi ty of hypertension in this pathological model. (C) 2000 Published by Elsevi er Science B.V. All rights reserved.