Comparison of haemoconcentration induced by big endothelin-1 and endothelin-1 in mice.
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.
Okumura
H
H
Pharmaceutical Res. Labs., Sapporo Breweries Ltd., Shizuoka, Japan.
Ashizawa
N
N
Kobayashi
F
F
Arai
K
K
Asakura
R
R
Ashikawa
N
N
Matsuura
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006400:Hematocrit; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011498:Protein Precursors / Q000494:pharmacology*
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D009320:Atrial Natriuretic Factor; C008890:phosphoramidon