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 r elaxation of norepinephrine (1 muM)-induced contractions. Calcitonin g ene-related peptide was antagonized by glybenclamide (1-100 muM), an i nhibitor of ATP-sensitive K+ channels, but not by tetraethylammonium ( 1 mM), an inhibitor of calcium2+-activated K+ channels. Glybenclamide (10 muM) produced a 6.7 fold and an 11-fold shift to the right of calc itonin gene-related peptide (0.1 to 100 nM) in uterine arteries from p regnant patients (n = 3) and nonpregnant patients (n = 6), respectivel y. 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 muM) did not reverse this relaxat ion (22.2 +/- 6.8%, n = 4 nonpregnant patients). Pinacidil (1 muM), an ATP-sensitive K+ channel opener, relaxed norepinehrine-induced contra ctions of uterine arteries. Glybenclamide (10 muM) also antagonized pi nacidil. These results suggest that calcitonin gene-related peptide re laxes norepinephrine-contracted human uterine arteries, at least in pa rt, by activation of a K+ channel, perhaps of the ATP-sensitive type.