Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats

The influence of bradykinin (BK) on blood glucose and plasma insulin levels was investigated in anaesthetized rats. Blood glucose level was dose‐dependently increased by intravenous infusion of BK. This effect of BK was enhanced by captopril, an inhibitor of angiotensin‐converting enzyme (ACE). Des‐Arg 9 ‐bradykinin (DABK), a kinin B 1 receptor agonist, did not modify blood glucose levels while the effect of BK was inhibited by Hoe‐140, a kinin B 2 receptor antagonist. The effect of BK was reduced by the NO‐synthase inhibitor, N ω ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME), and by the cyclo‐oxygenase inhibitor, indomethacin. The effect of BK was suppressed by the association of propranolol with phentolamine or phenoxybenzamine. It was also reduced by hexamethonium, a ganglion‐blocking drug. In adrenalectomized rats, the infusion of BK slightly decreased blood glucose levels. The hyperglycaemic effect of adrenaline was suppressed by propranolol associated with phentolamine or phenoxybenzamine, but it was not modified by L ‐NAME. Infusion of BK did not modify plasma insulin levels. However, after phentolamine and propranolol, BK induced a transient 2 fold rise in plasma insulin levels. The release of insulin was dose‐dependent and inhibited by Hoe‐140. We conclude that infusion of BK induces, via a stimulation of B 2 receptors, the release of NO and of prostanoids. The latter agents activate through a reflex pathway the release of catecholamines from the adrenal medulla. This release increases blood glucose levels and reduces plasma insulin levels. After adrenoceptor inhibition, BK induces a secretion of insulin, via the stimulation of B 2 receptors.British Journal of Pharmacology (2001) 134 , 1312–1318; doi: 10.1038/sj.bjp.0704374