Endothelium-dependent vascular activities of endothelin-like peptides in the isolated superior mesenteric arterial bed of the rat.

摘要

1. The vasoconstrictor activities of endothelin-2, endothelin-3, sarafotoxin S6b, human proendothelin1-38 and mouse vasoactive intestinal contractor (VIC) were studied in the isolated Krebs-Henseleit perfused mesenteric arterial bed of the rat in the presence and absence of the endothelium. The vasoconstrictor properties of endothelin-1 were studied in control preparations and in preparations treated with methylene blue or N omega-nitro-L-arginine methyl ester (NAME). Finally, the direct vasodilator properties of endothelin-2, endothelin-3 and sarafotoxin S6b were studied in preparations preconstricted with methoxamine. 2. In the presence of an intact endothelium, all of the peptides caused dose-dependent increases in perfusion pressure and sarafotoxin S6b was a full agonist relative to the other peptides studied (maximum increase in perfusion pressure, Rmax = 106 +/- 11 mmHg). Endothelin-1, endothelin-2 and VIC were more potent vasoconstrictors (ED50 93.0 +/- 40.0, 90.8 +/- 20.5 and 106 +/- 63 pmol, respectively) than endothelin-3 and sarafotoxin S6b, which were found to be equipotent (ED50 values 411 +/- 195 and 345 +/- 86 pmol, respectively). A full dose-response relationship could not be constructed for proendothelin, but the highest dose used (4 nmol) increased the perfusion pressure by 15.4 +/- 1.6 mmHg. 3. Destruction of the endothelium with the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS) significantly enhanced the pressor activity of all 5 peptides. The Rmax for sarafotoxin S6b was not significantly altered by removal of the endothelium but its potency was significantly increased (ED50 = 115 +/- 15 pmol).(ABSTRACT TRUNCATED AT 250 WORDS)