TY - JOUR
T1 - Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery
AU - Sokoya, Elke M.
AU - Burns, Alan R.
AU - Setiawan, Christopher T.
AU - Coleman, Harold A.
AU - Parkington, Helena C.
AU - Tare, Marianne
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Connexins
KW - Endothelium-derived hyperpolarizing factor
KW - Vascular smooth muscle
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U2 - 10.1152/ajpheart.01047.2005
DO - 10.1152/ajpheart.01047.2005
M3 - Article
C2 - 16443675
AN - SCOPUS:33745698602
SN - 0363-6135
VL - 291
SP - H385-H393
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1
ER -