Influence of calcitonin gene-related peptide release on pH-induced mechanical depression in rat atria

Rat atria is richly innervated by sensory nerve fibers that release CGRP wh en stimulated either by capsaicin or acid pH. We studied the physiological relevance of acid pH-induced CGRP release on changes in atrial contractilit y and relaxation produced by lowering the pH. Isolated atria electrically p aced at 2.77 Hz were exposed to a 10-minute period of metabolic acidosis (p H = 6.73 +/- 0.01, n=28) after: 1) CGRP release induced by capsaicin 0.5 mu M, 2) blockage of CGRP release with ruthenium red (RR) 5 muM; 3) no pretrea tment; and 4) CGRP receptor blockage with CGRP(8-37) 1 muM. Contractility a nd relaxation were significantly less depressed by acid pH when CGRP releas e was prevented by RR or CGRP receptor activation was blocked by CGRP(8-37) . The results suggest that CGRP release and the activation of CGRP receptor s may be physiologically involved in contributing to the depression of cont ractility and relaxation induced by acid pH in rat atria.