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.


METHODS
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 mumol/L) produced a concentration-dependent relaxation of norepinephrine (1 mumol/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 mumol/L), indomethacin (5 mumol/L), methylene blue (10 mumol/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 peptide1 receptors and does not involve beta-adrenoceptors, 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.
Nelson
S H
SH
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0749.
Steinsland
O S
OS
Suresh
M S
MS
D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy / Q000378:metabolism; D012016:Reference Values; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects
D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine