Desulfated hirugen (hirudin 54-65) induces endothelium-dependent relaxation of porcine pulmonary arteries.
Desulfated hirugen (hirudin 54-65) at concentrations from 0.1 to 2 microM was found to relax PGF2 alpha-precontracted ring segments of porcine pulmonary arteries with intact endothelium. The relaxation was associated with a pronounced increase in cGMP in the vessels. This endothelium-dependent relaxant effect depended on the extracellular calcium ion concentration and was probably due to the release of endothelium-derived NO as indicated by its susceptibility to blockade of the NO synthesis by NG-nitro-L-arginine. In the presence of indomethacin (3 microM) the maximum hirugen effect was significantly diminished by about 25%. In contrast, neither the sulfated hirugen nor recombinant desulfato hirudin at equimolar concentrations exerted endothelium-dependent relaxation. Hence, the relaxant effect did not correspond to the anticoagulant activity. Desulfated hirugen can be assigned to the group of well-known peptides causing vasodilatation via an endothelium-dependent mechanism.
Glusa
E
E
University of Jena, Medical School, Center for Vascular Biology and Medicine, Erfurt, Germany.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006629:Hirudins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D006629:Hirudins; D010446:Peptide Fragments; C091596:hirudin (54-65); D019335:Nitroarginine; D009569:Nitric Oxide; D008719:Methiothepin; D001285:Atropine; C065679:icatibant; D006632:Histamine; D001120:Arginine; D007650:Ketanserin; D002216:Captopril; D015237:Dinoprost; D006152:Cyclic GMP; D001920:Bradykinin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin; D010646:Phentolamine