Relaxation by calcitonin gene-related peptide may involve activation of K + channels in the human uterine artery

The vasodilatory role of calcitonin gene-related peptide in activating K + channels was examined in isolated, suffused human uterine arteries. Calcitonin gene-related peptide produced a concentration-dependent relaxation of norepinephrine (1 μM)-induced contractions. Calcitonin gene-related peptide was antagonized by glybenclamide (1–100 μM), an inhibitor of ATP-sensitive K + channels, but not by tetraethylammonium (1 mM), an inhibitor of calcium 2+-activated K + channels. Glybenclamide (10 μM) produced a 6.7 fold and an 11-fold shift to the right of calcitonin gene-related peptide (0.1 to 100 nM) in uterine arteries from pregnant patients (n = 3) and nonpregnant patients (n = 6), respectively. Calcitonin gene-related peptide (10 nM) less effectively (P < 0.05) relaxed contractions produced by KCl (50 mM) (29.4 ± 1.6%) than by norepinephrine and glybenclamide (10 μM) did not reverse this relaxation (22.2 ± 6.8%, n = 4 nonpregnant patients). Pinacidil (1 μM), an ATP-sensitive K + channel opener, relaxed norepinephrine-induced contractions of uterine arteries. Glybenclamide (10 μM) also antagonized pinacidil. These results suggest that calcitonin gene-related peptide relaxes norepinephrine-contracted human uterine arteries, at least in part, by activation of a K + channel, perhaps of the ATP-sensitive type.