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.