T-KININ HAS ENDOTHELIUM-DEPENDENT VASODILATOR ACTIVITY IN THE CAT

Responses to T-kinin, a peptide formed from the acute-phase substrate T-kininogen, were investigated in the hindlimb vascular bed of the cat . Under constant-flow conditions, injections of T-kinin into the perfu sion circuit in doses of 0.03-1 nmol induced rapid dose-related decrea ses in perfusion pressure. Responses to T-kinin were similar in time c ourse and magnitude to responses to bradykinin and kallidin and were i nhibited by the kinin B-2-receptor antagonist, Hoe-140. Responses to T -kinin were attenuated by an inhibitor of nitric oxide synthase and by tetraethylammonium chloride and were enhanced in dura by the guanosin e 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor zaprin ast. Responses to T-kinin were not altered by inhibitors of K-ATP(+) c hannels, by the cyclooxygenase pathway, or by muscarinic or beta-adren ergic-receptor antagonists. These data suggest that vasodilator respon ses to T-kinin are mediated by kinin B-2-receptor-stimulated release o f nitric oxide from the endothelium and increased smooth muscle cGMP l evels. These results indicate that activation of K-ATP(+) channels and muscarinic or beta-adrenergic receptors and the release of vasodilato r prostaglandins are not involved in mediating the response to T-kinin in the hindlimb circulation of the cat.