Calcitonin gene-related peptide and human epicardial coronary arteries: presence release and vasodilator effects.

摘要

1. In the present study, the levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) in human cardiopulmonary tissue were determined in combination with studies on CGRP-LI release from the left anterior descending coronary artery (LAD) and functional effects of CGRP on coronary arterial tone. 2. The highest levels of CGRP-LI were found in the LAD followed in declining order by the bronchus, right atrium, pulmonary artery, lung and left ventricle. 3. Exposure to capsaicin evoked a clear-cut increase in CGRP-LI outflow, suggesting release from isolated large specimen of the LAD. This release was Ca2(+)-dependent and was markedly attenuated by incubation with the mitochondrial Ca2(+)-inhibitor, ruthenium red. Exposure to potassium also released CGRP-LI in a Ca2(+)-dependent fashion from the LAD. 4. In functional experiments on human epicardial coronary arteries with an inner diameter of 0.4 to 0.8 mm, human CGRP alpha and beta relaxed the potassium-precontracted arteries equipotently. Substance P (SP) also relaxed these precontracted arteries but the relaxation could be prevented by incubation with methylene blue, an inhibitor of endothelium derived relaxing factor (EDRF)-mechanisms, which did not influence the effect of CGRP. 5. Capsaicin evoked a ruthenium red-sensitive relaxation of the potassium-precontracted arteries. However, ruthenium red did not affect the relaxations induced by CGRP or SP. Furthermore, the capsaicin effect was not influenced by methylene blue. 6. It is concluded that CGRP-LI is present in human cardiopulmonary tissue and can be released upon exposure to high concentrations of capsaicin as well as potassium.(ABSTRACT TRUNCATED AT 250 WORDS)