Kinin B₂ receptor‐mediated contraction of tail arteries from normal or streptozotocin‐induced diabetic rats

Abstract

1 The vasoactive eects of bradykinin (BK) are mediated by dierent subtypes of kinin receptors, of which the expression varies among dierent tissues. In rat tail artery tissues, BK elicited a concentrationdependent vasoconstriction (EC50, 25.9+2.4 nM; Emax, 0.39+0.01 g; n=16). This eect of BK was endothelium independent and indomethacin insensitive. The BK-induced contraction of tail artery tissues, however, depended on both membrane potential-sensitive extracellular Ca 2+ entry and thapsigargin-sensitive intracellular Ca 2+ release. 2 Kinin B 1 receptor antagonist or agonist did not aect the basal tension or the BK-induced contraction of tail artery tissues in the absence or presence of endothelium (P40.05). In contrast, the BK-induced vasoconstriction was inhibited by kinin B 2 receptor antagonists. Pretreatment of vascular tissues with Hoe 140 (1 nM) signi®cantly changed EC50 of the BK-induced vasoconstriction from 25.5+7.4 nM to 82.6+16.8 nM (n=8, P50.01) and Emax from 0.43+0.03 g to 0.16+0.01 g (n=8, P50.01). 3 In the tail artery tissues from streptozotocin-induced diabetic rats, the BK-elicited vasoconstriction was signi®cantly reduced (EC50, 67.8+11 nM; Emax, 0.19+0.01 g) compared to their counterparts from normal rats. The decreased vasoconstrictive eects of BK on diabetic arteries were endothelium independent and indomethacin insensitive. 4 Our study demonstrated that the contraction of rat tail arteries induced by BK was mediated by B 2 receptors located on vascular smooth muscles. The altered B 2 receptor-mediated vascular activity may play an important role in the vascular complications of diabetes.

Bradykinin stimulates ceramide production by activating specific BK-B1receptor in rat small artery

“…In general, it is the BK-B 2 receptor that is responsible for the contraction-inducing effect of BK on vessels such as the human umbilical vein (33), the rabbit jugular vein (33), and rat tail arteries (38) or for the BK-induced relaxation of pig coronary arteries (14,32) and pancreatic arteries (28). More importantly, the relaxation that is induced by BK in rat mesenteric arteries is also mediated by the BK-B 2 receptor (33,37 signals; however, it is known that ceramide and other sphingolipid metabolites are implicated in generating these signals including in smooth muscle cells (19,26,27).…”

Reduced Vasorelaxant Effect of Carbon Monoxide in Diabetes and the Underlying Mechanisms

“…To date, the altered functions of CO or the expression pattern of HO in diabetic vascular tissues had not been reported. The STZinduced experimental diabetes is a well-established animal model of diabetes, characterized with hyperglycemia and hypoinsulinemia (17)(18)(19). Using this diabetic animal model, we studied the vascular effects of CO in diabetes and the underlying mechanisms.…”

“…Because the vascular effect of CO was not dependent on the presence of an intact endothelium (4), endothelium was removed from vascular strips by a rubbing procedure. The absence of a functional endothelium was verified by the inability of acetylcholine (1 µmol/l) to induce relaxation of tail artery tissues as shown in our previous study (4,17). Concentration-response curves of the tissues to CO were obtained by accumulative addition of CO to the organ bath.…”

“…Measurement of isometric tension development of isolated rat tail artery tissues. The method for measurement of isometric tension development of isolated rat-tail artery tissues has been described previously (4,17,22). Briefly, tail arteries were isolated from rats.…”

“…These vascular complications are responsible for most of the morbidity and mortality of patients with diabetes and have been reproduced in both insulinopenic (15) and insulin-resistant rats (16). Altered vascular sensitivity to different vasoconstricting substances, such as bradykinin (17), changed properties of ion channels (18), and abnormal calcium handling in diabetic vascular SMCs (19) are among many putative mechanisms for the vascular complications of diabetes. The involvement of CO in the etiology of diabetes has been implicated as CO upregulated, whereas nitric oxide downregulated insulin secretion from pancreatic islets (20).…”