CAPSAZEPINE-SENSITIVE RELEASE OF CALCITONIN-GENE-RELATED PEPTIDE FROM C-FIBER AFFERENTS IN THE GUINEA-PIG HEART BY LOW PH AND LACTIC-ACID

The present study aimed to evaluate the possible influence of the selective capsaicin antagonist, capsazepine, on the release of calcitonin gene-related peptide (CGRP)-like immunoreactivity from sensory nerves in the isolated perfused guinea-pig heart. Low-pH buffer (pH 7, 6, 5), capsaicin (10(-7) M), lactic acid (5, 20, 50 mM) and nicotine (10(-4) M) all evoked a clear-cut release of CGRP-like immunoreactivity. Incubation with capsazepine (10(-6) to 10(-5) M) significantly reduced the CGRP-like immunoreactivity release evoked by low pH, capsaicin and lactic acid (5 mM) but not that evoked by nicotine. Furthermore, the capsaicin-evoked stimulation of heart rate was inhibited by incubation with capsazepine. The inorganic dye, ruthenium red, which has previously been shown to attenuate capsaicin-, but not nicotine-induced CGRP release from the heart, also reduced the release of CGRP caused by low pH and lactic acid (5 mM). It is concluded that the CGRP-like immunoreactivity release evoked from the heart by low pH and lactic acid shares several characteristic features with the release evoked by capsaicin. Since tissue pH is low in myocardial ischaemia and this is well known to cause pain, the use of capsazepine to inhibit the function of C-fibre afferents may represent a novel principle to influence autonomic reflex reactions associated with cardiac pathological conditions.