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The role of gap junctions in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation of human arteries was assessed using connexin mimetic peptides (CMPs) designated (37,43)Gap27, (40)Gap27, and (43)Gap26 according to homology with the major vascular connexins (Cx37, Cx40, and Cx43). Resistance arteries were obtained from subcutaneous fat biopsies of healthy pregnant women undergoing elective cesarean section. Endothelium-dependent vasodilatation to bradykinin (BK) was assessed using wire myography. N(omega)-nitro-l-arginine methyl ester (l-NAME) and indomethacin (nitric oxide synthase and cyclooxygenase inhibitors, respectively) attenuated maximal relaxation to BK (R(max)) by approximately 50%. Coincubation with l-NAME, indomethacin, and the combined CMPs ((37,43)Gap27, (40)Gap27, and (43)Gap26) almost abolished relaxation to BK (R(max) = 12.2 +/- 3.7%). In arteries incubated with l-NAME and indomethacin, the addition of either (37,43)Gap27 or (40)Gap27 had no significant effect on R(max), whereas (43)Gap26 caused marked inhibition (R(max) = 21 +/- 6.4%, P = 0.005 vs. l-NAME plus indomethacin alone) that was similar to that of the triple combination. Endothelium-independent vasorelaxation was unaffected by CMPs, l-NAME, or indomethacin. Immunohistochemistry demonstrated Cx37, Cx40, and Cx43 expression in the endothelium and vascular smooth muscle. In pregnant women, EDHF-mediated vasorelaxation of subcutaneous resistance arteries is dependent on Cx43 and gap junctions.

Original publication

DOI

10.1152/ajpheart.00797.2006

Type

Journal article

Journal

Am j physiol heart circ physiol

Publication Date

02/2007

Volume

292

Pages

H1026 - H1032

Keywords

Adult, Arteries, Biological Factors, Bradykinin, Connexin 43, Connexins, Cyclooxygenase Inhibitors, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Gap Junctions, Humans, Indomethacin, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase, Oligopeptides, Peptides, Pregnancy, Subcutaneous Fat, Vasodilation, Vasodilator Agents, Gap Junction alpha-5 Protein, Gap Junction alpha-4 Protein