Pressor and pulmonary responses to ET-1(1–31) in guinea-pigs

摘要: Endothelin-1(1–31) (ET-1(1–31); 0.25 to 4 nmol kg−1; i.v.) induced, in the guinea-pig, graded increases MAP and an indomethacin-sensitive enhancement of pulmonary insufflation pressure (PIP). At all doses, ET-1(1–31) induced a monophasic pressor response, except at kg−1, which caused rapid transient response (first phase: over first 10 min after injection) followed by more slowly-developing sustained (second between 45 increase MAP. was fold less potent than ET-1 on PIP responses. Phosphoramidon (5 mg kg−1) reduced both effects ET-1(1–31). Thiorphan (0.25 2.5 did not affect responses although its were markedly NEP inhibitor. A selective endothelin-converting enzyme (ECE) inhibitor, CGS 35066 (1 kg−1), significantly second phase triggered ET-1(1–31). The (but first) (4 BQ-123 (selective ETA antagonist), whereas BQ-788 ETB antagonist). Co-administration plus abolished ET-1(1–31)-induced PIP, but blockade afforded now reversed. In guinea-pig isolated perfused lungs, (50 nM) release prostacyclin thromboxane A2, inhibited or thiorphan (25 μM), μM). These results suggest that enhances Its sustained, transient, are mediated via receptor activation. Furthermore, airway resistance vivo triggers A2 from lungs predominantly failed display any selectivity action towards either receptors these models. We that, order raise MAP, requires conversion ET-1, ECE lesser extent neutral endopeptidase 24.11, reverse holds true regarding pharmacological airways. British Journal Pharmacology (2002) 136, 819–828. doi:10.1038/sj.bjp.0704782