Centrally bradykinin B2-receptor-induced hypertensive and positive chronotropic effects are mediated via activation of the sympathetic nervous system.

OBJECTIVE

The presence of bradykinin B2 receptors in the cardiovascular regulatory centres of the brain indicates that increase in mean arterial pressure (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, and (iii) plasma arginine vasopressin (AVP) levels were determined. In addition, following blockade of peripheral alpha1 -adrenoceptors with prazosin (50 and 250 microg/kg i.v.) beta1-adrenoceptors with atenolol (10 mg/kg i.v.) or V1 -receptors with TMe-AVP (Manning compound) (10 microg/kg i.c.v. and 100 microg/kg i.v.) the effects of bradykinin (100 pmol i.c.v.) on MAP and heart rate were determined.

RESULTS

Bradykinin increased MAP and heart rate dose-dependently. The pressor effects of 100 pmol bradykinin i.c.v. were completely blocked by pretreatment with the specific B2 receptor antagonist Hoe 140 (3 pmol, i.c.v.). There was no change in plasma dopamine, noradrenaline, adrenaline or AVP levels after increasing doses of bradykinin. However, peripheral blockade of alpha1- and beta1-adrenoceptors reduced the bradykinin-induced increase in MAP and heart rate, whereas central and peripheral V1 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 sympathoneuronal rather than sympathoadrenal pathway in vivo.