Acute alveolar hypoxia increases endothelin-1 release but decreases release of calcitonin gene-related peptide in isolated perfused rat lungs.

The release and vascular effects of calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) during acute alveolar hypoxia (O2 2%) were examined in isolated blood-perfused rat lungs. In 10 lungs, repeatedly ventilated with hypoxic gas for 5 min, samples from effluent blood were taken during hypoxia and analysed for plasma levels of CGRP-like immunoreactivity (-LI) and ET-1-LI. The plasma levels of ET-1-LI were significantly (p < 0.05) increased in hypoxic lungs (5.5 +/- 0.5 pmol l-1) compared with normoxic controls (3.7 +/- 0.56 pmol l-1). Plasma levels of CGRP-LI were significantly (p < 0.01) lower in hypoxic lungs (43.9 +/- 2.9 pmol l-1) than in normoxic controls (55.5 +/- 4.0 pmol l-1). No significant correlation was seen between perfusate peptide levels and pulmonary artery pressure (Ppa) during ventilation with normoxic or hypoxic gas. Infusion of the CGRP receptor blocker, CGRP, did not influence either the baseline Ppa or the development of the hypoxic pulmonary vasoconstriction response (HPV). In lungs undergoing HPV, 2 nmol l-1 ET-1 added to the perfusate, significantly reduced the hypoxic pressor response by 14 +/- 3% (p < 0.05), while addition of 200 nmol l-1 ET-1 caused no significant changes in HPV. CGRP 2 nmol l-1 caused no significant attenuation of HPV (8.9%), while 200 nmol l-1 CGRP significantly reduced HPV by 16 +/- 5% (p < 0.05). To conclude: acute alveolar hypoxia changes release of CGRP and ET-1 to the perfusate in isolated rat lungs. The results further suggest that CGRP and ET-1 are not involved in the development and regulation of the hypoxic pulmonary vasoconstriction response.