Possible physiologic role of calcitonin gene-related peptide in the human uterine artery

Objective : The purpose of our study was to determine the potential physiologic role of calcitonin gene-related peptide as an endogenous vasodilator of human uterine arteries during pregnancy. Study design : Isolated, suffused uterine arteries from pregnant patients ( n = 9) and nonpregnant patients ( n = 19) were used in the study. Results : Calcitonin gene-related peptide (1 nmol/L to 0.1 μmol/L) produced a concentration-dependent relaxation of norepinephrine (1 μmol/L)-induced contractions. The values of calcitonin gene-related peptide that inhibited norepinephrine-induced contractions by 50% were 0.9 ± 0.7 nmol/L ( n = 8) and 6.5 ± 1.5 nmol/L ( n = 12) in pregnant and nonpregnant arteries, respectively. The calcitonin gene-related peptide-induced relaxation was not affected by propranolol (1 μmol/L), indomethacin (5 μmol/L), methylene blue (10 μmol/L), or by the removal of the endothelium. The relaxant effect of calcitonin gene-related peptide was inhibited by human calcitonin gene-related peptide (8.37) . The endogenous levels of calcitonin gene-related peptide were 110.2 ± 13.5 pmol/L/gm wet weight in pregnant arteries and 14.8 ± 3.2 pmol/L/gm wet weight in nonpregnant arteries. Conclusions : These results demonstrate that the vasodilatory effect of calcitonin gene-related peptide is mediated by calcitonin gene-related peptide, receptors and does not involve s-adrenoeeptors, vasodilator prostanoids, increased levels of guanosine 3′,5′-cyclic monophosphate, or endothelium-derived relaxing factor. The findings that calcitonin gene-related peptide acts as a potent dilator and that pregnancy increases both the sensitivity to calcitonin gene-related peptide and the endogenous levels of calcitonin gene-related peptide support the view that calcitonin gene-related peptide has a physiologic role in dilating the uterine vasculature, especially during pregnancy.