| Autor: |
Schmeck, Joachim, Gluth, Heidi, Mihaljevic, Nicolas, Born, Michael, Wendel-Wellner, Martina, Krafft, Peter |
| Zdroj: |
Journal of Applied Physiology; December 1999, Vol. 87 Issue: 6 p2284-2289, 6p |
| Abstrakt: |
Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ETAor ETBreceptors, 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 (10−8M;n= 6; control) was injected after pretreatment with the ETA-receptor antagonist BQ-123 (10−6M;n= 6) or the ETB-receptor antagonist BQ-788 (10−6M;n= 6). The same protocol was carried out in part IIafter 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 andP< 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 ETAreceptors. BQ-788 treatment resulted in even more pronounced vasoconstriction. After pulmonary preconstriction, ETAantagonism exerted no effects on PAP, whereas ETBantagonism blocked the PAP increase. Therefore, ET-1-induced pulmonary vasoconstriction is shifted from an ETA-related to an ETB-mediated mechanism after pulmonary vascular preconstriction. |
| Databáze: |
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