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

Abstract

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 irnmunoreactivity (-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 pmol 1⁻¹). Plasma levels of CGRP-LI were significantly (p<0.01) lower in hypoxic lungs (43.9 ± 2.9 pmol 1⁻¹) than in normoxic controls (55.5 ± 4.0 pmol 1⁻¹). 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_8-37, did not influence either the baseline Ppa or the development of the hypoxic pulmonary vasoconstriction response (HPV). In lungs undergoing HPV, 2 nmol 1⁻¹ ET-1 added to the perfusate, significantly reduced the hypoxic pressor response by 14 ± 3% (p<0.05), while addition of 200 nmol 1⁻¹ ET-1 caused no significant changes in HPV. CGRP 2 nmol 1⁻¹ caused no significant attenuation of HPV (8.9%), while 200 nmol 1⁻¹ 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.

Key Words:

• CGRP
• ET-1
• hypoxic pulmonary vasoconstrictor response