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.
Department of Physiology, Colorado State University, Fort Collins 80523.
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PL
Janssen
A
A
Tucker
D000064:Acclimatization / Q000502:physiology; D000531:Altitude; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002245:Carbon Dioxide / Q000097:blood; D006400:Hematocrit; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D000804:Angiotensin II; C058636:calcitonin gene-related peptide (8-37); D002245:Carbon Dioxide; D015740:Calcitonin Gene-Related Peptide; D010100:Oxygen