ATTENUATION OF LOW PH-EVOKED, BUT NOT CAPSAICIN-EVOKED OR PGI(2)-EVOKED CGRP-RELEASE BY ENDOTHELIUM REMOVAL USING SAPONIN

The aim of the present study was to evaluate the role of the endotheli um in low pH-, capsaicin-, and prostacyclin (PGI(2))-evoked release of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) fr om C-fibre afferents in the isolated, perfused guinea-pig heart. CGRP- LI release, and formation of the stable PGI(2)-metabolite 6-keto-PGF(1 alpha) in response to moderate acidosis (pH 7, 6, but not 5) were sig nificantly reduced after removal of the endothelium using saponin (50 mu g 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 rem oval of the endothelium. Saponin treatment did not influence the vasod ilator 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 endo thelium 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.