Centrally bradykinin B-2-receptor-induced hypertensive and positive chronotropic effects are mediated via activation of the sympathetic nervous system

Objective The presence of bradykinin Ba receptors in the cardiovascular reg ulatory centres of the brain indicates that increase in mean arterial press ure (MAP) and heart rate after intracerebroventricular (i.c.v.) injections of bradykinin is mediated via stimulation of sympathetic nervous system. Methods Adult Wistar-Kyoto (WKY) rats were instrumented chronically with an i.c.v. cannula, and the catheters were placed into the femoral artery and vein. Increasing doses of bradykinin (1-300 pmol) were given i.c.v. and (i) MAP and heart rate, (ii) plasma dopamine, noradrenaline and adrenaline, an d (iii) plasma arginine vasopressin (AVP) levels were determined. In additi on, following blockade of peripheral alpha(1)-adrenoceptors with prazosin ( 50 and 250 mu g/kg i.v.) beta(1)-adrenoceptors with atenolol (10 mg/kg i.v. ) or V-1-receptors with TMe-AVP (Manning compound) (10 mu g/kg i.c.v. and 1 00 mu g/kg i.v.) the effects of bradykinin (100 pmol i.c.v.) on MAP and hea rt rate were determined. Results Bradykinin increased MAP and heart rate dose-dependently. The press er effects of 100 pmol bradykinin i.c.v. were completely blocked by pretrea tment with the specific B-2 receptor antagonist Hoe 140 (3 pmol, i.c.v.). T here was no change in plasma dopamine, noradrenaline, adrenaline or AVP lev els after increasing doses of bradykinin. However, peripheral blockade of a lpha(1)- and beta(1)-adrenoceptors reduced the bradykinin-induced increase in MAP and heart rate, whereas central and peripheral V-1 receptor blockade did not alter the cardiovascular responses to i.c.v. bradykinin. Conclusion Our data suggest that the hypertensive and positive chronotropic effects induced by i.c.v. bradykinin are due to stimulation of sympathoneu ronal rather than sympathoadrenal pathway in vivo. J Hypertens 1999, 17:126 5-1271 (C) Lippincott Williams & Wilkins.