Kinin B2 receptor-mediated contraction of tail arteries from normal or streptozotocin-induced diabetic rats.
1. The vasoactive effects of bradykinin (BK) are mediated by different subtypes of kinin receptors, of which the expression varies among different tissues. In rat tail artery tissues, BK elicited a concentration-dependent vasoconstriction (EC50, 25.9+/-2.4nM; Emax, 0.39+/-0.01 g; n=16). This effect of BK was endothelium independent and indomethacin insensitive. The BK-induced contraction of tail artery tissues, however, depended on both membrane potential-sensitive extracellular Ca2+ entry and thapsigargin-sensitive intracellular Ca2+ release. 2. Kinin B1 receptor antagonist or agonist did not affect the basal tension or the BK-induced contraction of tail artery tissues in the absence or presence of endothelium (P>0.05). In contrast, the BK-induced vasoconstriction was inhibited by kinin B2 receptor antagonists. Pretreatment of vascular tissues with Hoe 140 (1 nM) significantly changed EC50 of the BK-induced vasoconstriction from 25.5+/-7.4 nM to 82.6+/-16.8nM (n=8, P<0.01) and Emax from 0.43+/-0.03g to 0.16+/-0.01 g (n=8, P<0.01). 3. In the tail artery tissues from streptozotocin-induced diabetic rats, the BK-elicited vasoconstriction was significantly reduced (EC50, 67.8+/-11 nM: Emax, 0.19+/-0.01 g) compared to their counterparts from normal rats. The decreased vasoconstrictive effects 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 B2 receptors located on vascular smooth muscles. The altered B2 receptor-mediated vascular activity may play an important role in the vascular complications of diabetes.
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
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D000818:Animals; D001158:Arteries / Q000503:physiopathology; D001920:Bradykinin / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D013311:Streptozocin; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013311:Streptozocin; D001920:Bradykinin