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 (C GRP) and endothelin-l (ET-1) during acute alveolar hypoxia (O-2 2%) we re examined in isolated blood-perfused rat lungs. In 10 lungs, repeate dly 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 1(-1)) compared with normoxic controls (3.7 +/- 0.56 pmol1(-1)). Plasm a levels of CGRP-LI were significantly (p < 0.01) lower in hypoxic lun gs (43.9 +/- 2.9 pmol1(-1)) than in normoxic controls (55.5 +/- 4.0 pm ol1(-1)). No significant correlation was seen between perfusate peptid e levels and pulmonary artery pressure (Ppa) during ventilation with n ormoxic or hypoxic gas. Infusion of the CGRP receptor blocker, CGRP(8- 37); did not influence either the baseline Ppa or the development of t he hypoxic pulmonary vasoconstriction response (HPV). In lungs undergo ing HPV, 2 nmol I-L ET-1 added to the perfusate, significantly reduced the hypoxic presser response by 14 +/- 3% (p < 0.05), while addition of 200 nmol1(-1) ET-1 caused no significant changes in HPV. CGRP 2 nmo l1(-1) caused no significant attenuation of HPV (8.9%), while 200 nmol 1(-1) CORP significantly reduced HPV by 16 +/- 5% (p < 0.05). To concl ude: acute alveolar hypoxia changes release of CGRP and ET-1 to the pe rfusate in isolated rat lungs. The results further suggest that CGRP a nd ET-1 are not involved in the development and regulation of the hypo xic pulmonary vasoconstriction response.