Abstract
Objective:To observe pulmonary arteriolar effects of endothelin-1 (ET-1) in the intact lung and determine if constriction to ET-1 is potentiated by inhibition of nitric oxide (NO) synthesis. Methods:In anesthetized male Sprague-Dawley rats with open chest, the lungs were ventilated with air through the lower trachea and in vivoresponses of pulmonary arterioles were examined by video microscopy. Observations were made when the lungs were statically inflated with oxygen to a pressure of approximately 10 cm H2O for brief periods. A lens with a dipping cone was held at the pleural surface. ET-1 (10−7–10−5 M; approximately 0.1 ml) was applied topically to the fluid layer under the dipping cone. Results:ET-1 (10−6 M) constricted parent arterioles 60 ± 5 µm in diameter by 52 ± 12% (range: 20–100%) and branches 45 ± 3 µm in diameter by 36 ± 4% (19–48%). Constriction persisted and there was a dramatic long-lasting decrease in flow. Alveolar walls quickly became pale, indicating reduced capillary perfusion. A lower concentration of ET-1 (10−7 M) constricted (p< 0.05) parent arterioles 61 ± 4 µm in diameter by 7 ± 3% initially, and by 13 ± 8% after 14 ± 2 minutes, while smaller branches did not respond. In separate experiments, infusion of the NO synthase inhibitor L-NAME (1 mg/kg per minute), modestly (10 ± 3%) decreased (p< 0.05) baseline parent arteriolar diameter from 72 ± 7 µm to 64 ± 5 µm. Branch diameter changed insignificantly from 42 ± 7 µm to 38 ± 7 µm. After L-NAME, ET-1 (10−7 M) constricted (p< 0.05) parent arterioles by 17 ± 4% initially and 40 ± 14% after 14 ± 2 minutes. Concurrently, branches constricted (p< 0.05) by 14 ± 4% and 26 ± 15%. Conclusions:Arterioles less than 80 µm in diameter were very responsive to ET-1, which could be a factor in altering pulmonary microvascular resistance. Inhibition of NO synthesis appears to potentiate constriction to ET-1.