In:
Journal of Applied Physiology, American Physiological Society, Vol. 87, No. 6 ( 1999-12-01), p. 2284-2289
Abstract:
Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ET A or ET B receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone ( part I) and after preconstriction (U-46619; part II). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I, ET-1 (10 −8 M; n = 6; control) was injected after pretreatment with the ET A -receptor antagonist BQ-123 (10 −6 M; n = 6) or the ET B -receptor antagonist BQ-788 (10 −6 M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase (ΔPAP 4.3 ± 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 ( P 〈 0.05 at 10 min and P 〈 0.01 thereafter) and that was more pronounced after BQ-788 ( P 〈 0.01 at 10 min and P 〈 0.001 thereafter). In part II, ET-1 induced an immediate rise in PAP with a maximum after 5 min (ΔPAP 6.3 ± 1.4 mmHg), leveling off at ΔPAP 3.2 ± 0.2 mmHg after 15 min. Pretreatment with BQ-123 failed to attenuate the increase. BQ-788 significantly reduced the peak pressure at 5 min (0.75 ± 0.4 mmHg; P 〈 0.001) as well as the plateau pressure thereafter ( P 〈 0.01). We conclude that ET-1 administration causes pulmonary vasoconstriction independent of basal vascular tone, and, at normal vascular tone, the vasoconstriction seems to be mediated via ET A receptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ET A antagonism exerted no effects on PAP, whereas ET B antagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ET A -related to an ET B -mediated mechanism after pulmonary vascular preconstriction.
Type of Medium:
Online Resource
ISSN:
8750-7587
,
1522-1601
DOI:
10.1152/jappl.1999.87.6.2284
Language:
English
Publisher:
American Physiological Society
Publication Date:
1999
detail.hit.zdb_id:
1404365-8
SSG:
12
SSG:
31
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