CARDIOVASCULAR-RESPONSES ELICITED BY INTRATHECAL KININS IN THE CONSCIOUS RAT

In the conscious, unrestrained rat, intrathecal (i.1.) injection of 0.81 pmol 81 nmol bradykinin (BK), kallidin (KD) and T-kinin at the T-9 spinal cord level produced transient (< 10 min) increases in mean arterial pressure (MAP) and longer lasting decreases in heart rate (IIR). These effects were dose-dependent and similar with respect to intensity and time course for the three kinins. The des-Arg9-BK fragment, a selective agonist for B1 receptors, was active only at 81 nmol. The pressor response induced by BK was enhanced by propranolol and by transection of the cervical spinal cord but was converted to a vasodepressor effect by prazosin. The bradycardia was converted to tachycardia by prazosin, atropine, pentolinium, capsaicin and in spinal transected rats. However, the cardiovascular responses to BK remained unaffected by diphenhydramine plus cimetidine, morphine, indomethacin, adrenal medullectomy. i.t. idazoxan and after bulbospinal noradrenaline deafferentation with 6-hydroxydopamine. These results suggest that the increase in MAP induced by i.t. BK is mediated by the sympathoadrenal system while the decrease in HR is ascribable to a vagal reflex involving sensory C-fibers and a spinobulbar pathway. This pharmacological evidence therefore supports a role for kinins in cardiovascular regulation in the spinal cord.