Calcitonin gene-related peptide modulates pulmonary vascular reactivity in isolated rat lungs

The role of calcitonin gene-related peptide (CGRP) in modulating hypoxic pulmonary vasoconstriction was assessed. The effects of CGRP and its antagonist [CGRP-(8-37)] on responses to acute hypoxia (3% O2) and angiotensin II (ANG II; 0.4 microgram) were studied in isolated lungs of male Sprague-Dawley rats perfused with a salt solution. Rats with pulmonary hypertension, induced by simulated altitude exposure, were also used to determine the actions of CGRP in a remodeled pulmonary vascular bed. In normotensive (NT) and altitude-exposed (AE) lungs, CGRP injections (10 nM), given after stable pressor responses were attained, attenuated (P < 0.05) subsequent hypoxic pressor responses. Pretreatment with CGRP-(8-37) (10 nM) enhanced (P < or = 0.05) initial ANG II-induced pressor responses in both AE and NT lungs. CGRP-(8-37) pretreatment (10 nM) had little influence on the hypoxic pressor responses in either NT or AE lungs. Results indicate that CGRP modulates hypoxic pulmonary vasoconstriction and that CGRP-(8-37) enhances pressor responses to ANG II in NT and AE rat lungs.