Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery

Elke M. Sokoya, Alan R. Burns, Christopher T. Setiawan, Harold A. Coleman, Helena C. Parkington, Marianne Tare

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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 Nω-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 × 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 μm 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number1
DOIs
Publication statusPublished - 2006

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Keywords

  • Connexins
  • Endothelium-derived hyperpolarizing factor
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology

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