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Comparison of haemoconcentration induced by big endothelin‐1 and endothelin‐1 in mice
Author(s) -
Okumura Hiroshi,
Ashizawa Naoki,
Kobayashi Fujio,
Arai Koshi,
Asakura Rieko,
Ashikawa Nami,
Matsuura Akihiro
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13975.x
Subject(s) - phosphoramidon , endothelin receptor , medicine , endocrinology , endothelin 1 , pathogenesis , chemistry , endothelins , endothelin 3 , biology , receptor
1 The profile of haemoconcentration induced by big endothelin‐1 (big ET‐1), a precursor of endothelin‐1 (ET‐1), was compared with that induced by endothelin‐1 in mice. 2 ET‐1(1.5 nmol kg −1 , i.v.) increased haematocrit in mice, which reached a maximum at 5 min and then returned to the control value within 30 min after the administration, this occurred at the same time as changes in the plasma immunoreactive endothelin‐1 and rat atrial natriuretic peptide (rANP)‐like activities (IR‐ET‐1 and IR‐rANP, respectively). 3 Big ET‐1(2.5–15 nmol kg −1 , i.v.) also caused a significant and dose‐dependent increase in haematocrit, that lasted over 3 h although elevated plasma IR‐ET‐1 and IR‐rANP had almost been restored to the initial levels within 10 min after big ET‐1 injection. 4 A metalloproteinase inhibitor, phosphoramidon (10 mg kg −1 , i.v.), which inhibits the activity of endothelin converting enzyme (ECE), delayed the onset of big ET‐1‐induced haemoconcentration, but failed to alter the maximal value and the duration of the haemoconcentration. 5 Pretreatment with phosphoramidon (10 mg kg −1 , i.v.) did not affect the big ET‐1‐induced change in plasma IR‐ET‐1, while significant delay of the disappearance of plasma IR‐rANP and significant suppression of a sustained increase in tissue IR‐ET‐1 were observed. 6 These results suggest that ET‐1, not in plasma but in tissue, plays an important role in the pathogenesis of big ET‐1‐induced long‐lasting haemoconcentration, in which unknown factors besides rANP are involved.