title: Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery.
abstract: The mechanisms underlying endothelium-dependent hyperpolarizing factor (EDHF) in the middle cerebral artery (MCA) remain largely unresolved. In particular, very little is known regarding the way in which the signal is transmitted from endothelium to smooth muscle. The present study tested the hypothesis that direct communication via myoendothelial gap junctions contributes to the EDHF response in the male rat MCA. EDHF-mediated dilations were elicited in rat MCAs by luminal application of ATP or UTP in the presence of Nomega-nitro-L-arginine methyl ester and indomethacin. Maximum dilation to luminal ATP (10(-4) M) was reduced significantly after incubation with a gap peptide cocktail (9 +/- 4%, n = 6) compared with a scrambled gap peptide cocktail (99 +/- 1%, n = 6, P < 0.05). A gap peptide cocktail had no effect on amplitude of endothelial cell hyperpolarization in response to 3 x 10(-5) M UTP (22 +/- 3 vs. 22 +/- 1 mV, n = 4), whereas smooth muscle cell hyperpolarization was significantly attenuated (17 +/- 1 vs. 6 +/- 1 mV, n = 4, P = 0.004). Connexin (Cx) 37 was localized to smooth muscle and Cx43 to endothelium, whereas Cx40 was found in endothelium and smooth muscle. Electron microscopy revealed the existence of frequent myoendothelial junctions. The total number of myoendothelial junctions per 5 microm of MCA sectioned was 2.5 +/- 0.5. Our results suggest that myoendothelial communication contributes to smooth muscle cell hyperpolarization and EDHF dilation in male rat MCA.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, Houston, TX 77030, USA. egolding@bcm.tmc.edu
authors.forename: Elke M
authors.initials: EM
authors.lastname: Sokoya
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Setiawan
authors.forename: Harold A
authors.initials: HA
authors.lastname: Coleman
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D019317:Evidence-Based Medicine; D017629:Gap Junctions / Q000502:physiology*; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D014664:Vasodilation / Q000502:physiology*
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor