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 perfusion circuit in doses of 0.03-1 nmol induced rapid dose-related decreases in perfusion pressure. Responses to T-kinin were similar in time course and magnitude to responses to bradykinin and kallidin and were inhibited by the kinin B2-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 duration by the guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor zaprinast. Responses to T-kinin were not altered by inhibitors of K+(ATP) channels, by the cyclooxygenase pathway, or by muscarinic or beta-adrenergic-receptor antagonists. These data suggest that vasodilator responses to T-kinin are mediated by kinin B2-receptor-stimulated release of nitric oxide from the endothelium and increased smooth muscle cGMP levels. These results indicate that activation of K+(ATP) channels and muscarinic or beta-adrenergic receptors and the release of vasodilator prostaglandins are not involved in mediating the response to T-kinin in the hindlimb circulation of the cat.
Santiago
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Champion
H C
HC
Kadowitz
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002415:Cats; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D006834:Hydrazines / Q000494:pharmacology; D007609:Kallidin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009589:Nitrogen Oxides; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects*; D026423:S-Nitroso-N-Acetylpenicillamine; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D006834:Hydrazines; D009589:Nitrogen Oxides; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D007609:Kallidin; D019789:Tetraethylammonium; D026423:S-Nitroso-N-Acetylpenicillamine; C065679:icatibant; C039065:T-kinin; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D010396:Penicillamine; D015773:Enalaprilat; D000109:Acetylcholine; D000420:Albuterol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester