J. Damas et al., Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats, BR J PHARM, 134(6), 2001, pp. 1312-1318
1 The influence of bradykinin (BK) on blood glucose and plasma insulin leve
ls was investigated in anaesthetized rats.
2 Blood glucose level was dose-dependently increased by intravenous infusio
n of BK. This effect of BK was enhanced by captopril, an inhibitor of angio
tensin-converting enzyme (ACE). Des-Arg(9)-bradykinin (DABK), a kinin B-1 r
eceptor 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 B
K was reduced by the NO-synthase inhibitor, N-omega-nitro-L-arginine methyl
ester (L-NAME), and by the cyclo-oxygenase inhibitor, indomethacin.
3 The effect of BK was suppressed by the association of propranolol with ph
entolamine or phenoxybenzamine. It was also reduced by hexamethonium, a gan
glion-blocking drug. In adrenalectomized rats, the infusion of BK slightly
decreased blood glucose levels.
4 The hyperglycaemic effect of adrenaline was suppressed by propranolol ass
ociated with phentolamine or phenoxybenzamine, but it was not modified by L
-NAME.
5 Infusion of BK did not modify plasma insulin levels. However, after phent
olamine and propranolol, BK induced a transient 2 fold rise in plasma insul
in levels. The release of insulin was dose-dependent and inhibited by Hoe-1
40.
6 We conclude that infusion of BK induces, via a stimulation of B-2 recepto
rs, the release of NO and of prostanoids. The latter agents activate throug
h a reflex pathway the release of catecholamines from the adrenal medulla.
This release increases blood glucose levels and reduces plasma insulin leve
ls. After adrenoceptor inhibition, BK induces a secretion of insulin, via t
he stimulation of B-2 receptors.