Attenuation of low pH-, but not capsaicin- or PGI2- evoked CGRP - release by endothelium removal using saponin

The aim of the present study was to evaluate the role of the endothelium in low pH-, capsaicin-, and prostacyclin (PGI 2 )-evoked release of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from C-fibre afferents in the isolated, perfused guinea-pig heart. CGRP-LI release, and formation of the stable PGI 2 -metabolite 6-keto-PGF 1α , in response to moderate acidosis (pH 7, 6, but not 5) were significantly reduced after removal of the endothelium using saponin (50 μg mL -1 ) perfusion. In contrast, the release of CGRP-LI evoked by capsaicin (10 -7 M) or PGI 2 (10 -5 M) remained unchanged after removal of the endothelium. Saponin treatment did not influence the vasodilator action of CGRP, whereas the vasodilation evoked by substance P (SP) was abolished. It is concluded that CGRP release evoked by low pH, but not that evoked by capsaicin or exogenous PGI 2 , is partly endothelium dependent. Our data suggest that endothelially produced PGI 2 is involved in low pH-evoked release of CGRP from capsaicin sensitive nerves in the heart.