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

Abstract

1 The in¯uence of bradykinin (BK) on blood glucose and plasma insulin levels was investigated in anaesthetized rats. 2 Blood glucose level was dose-dependently increased by intravenous infusion of BK. This eect 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 eect of BK was inhibited by Hoe-140, a kinin B 2 receptor antagonist. The eect of BK was reduced by the NO-synthase inhibitor, N o -nitro-L-arginine methyl ester (L-NAME), and by the cyclo-oxygenase inhibitor, indomethacin. 3 The eect 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. 4 The hyperglycaemic eect of adrenaline was suppressed by propranolol associated with phentolamine or phenoxybenzamine, but it was not modi®ed by L-NAME. 5 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. 6 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 re¯ex 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.

Nitric Oxide Inhibits the Bradykinin B2 Receptor-Mediated Adrenomedullary Catecholamine Release but Has No Effect on Adrenal Blood Flow Response In Vivo

“…In the present study, we showed that the local administration of BK increased adrenal catecholamine secretion without any significant changes in the systemic parameters such as mean aortic pressure, heart rate, and circulating catecholamine levels in aortic blood. These observations are consistent with the view that the increasing effect of BK on catecholamine secretion resulted from its direct action on the adrenal medulla and not from secondary factors such as a reflex-induced increase in sympathetic outflow that can be observed under certain conditions in vivo (28).…”

The enhancement of the hyperglycemic effect of S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine by vitamin C in an animal model

“…Reports on the metabolic effects of captopril on oral glucose tolerance and insulin action in the literature are conflicting. Studies have shown that captopril enhanced the effects of bradykinin, which via a stimulation of B 2 receptors caused the release of NO and of prostanoids, which resulted in increased blood glucose levels and reduced plasma insulin levels [20]. However the results from this study showed that captopril had no effect on oral glucose tolerance and insulin levels, and plasma nitrate/nitrite levels in captopril-treated dogs was comparable with age-matched controls administered with water.…”

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

“…The release of adrenaline increases blood glucose and simultaneously inhibits insulin secretion. Indeed, in rats treated with α-and β-adrenergic blockers, BK induced an increase in plasma level of insulin associated with a decrease in blood glucose [89].…”

“…Moreover, as we have demonstrated [25], the administration of a glucose load in kininogendeficient rats induced a larger hyperglycemia but a smaller increase in plasma level of insulin than in normal rats. These latter observations led us to study the influence of intravenous administration of BK on blood glucose level and plasma insulin level [88,89]. Intravenous injection of BK did not induce any significant changes in these parameters during one hour, while hypotensive responses were easily elicited by bolus injection of this peptide.…”