Role of Rho-kinase in mediating contraction of chicken embryo femoral arteries.
Rho-kinase-dependent Ca2+ sensitization is an essential process for contraction of mammalian vascular smooth muscle but the information about its effects in non-mammalian vessels is scarce. We aimed to investigate, using the Rho-kinase inhibitor hydroxyfasudil, the potential role of the Rho-kinase pathway of Ca2+ sensitization in depolarization- and agonist-mediated contraction of chicken embryo (at day 19 of the 21 days of incubation) femoral arteries. Contraction elicited by KCl (125 mM) comprised two phases (phasic and tonic contraction), both of which were abolished in the absence of extracellular Ca2+. Hydroxyfasudil (10 microM) left the initial phasic component nearly intact but abolished the tonic component. Hydroxyfasudil also induced a marked impairment of the contractions elicited by phenylephrine (PE), the thromboxane A2 mimetic U46619, and endothelin-1. In contrast, inhibition of protein kinase C (PKC) by chelerythrine did not affect KCl- or PE-induced contractions, indicating lack of participation of PKC-mediated Ca2+ sensitization. Incubation under chronic hypoxia (15% O2 from day 0) impaired embryonic growth but did not significantly affect hydroxyfasudil-mediated relaxation. In summary, our findings are indicative of a role for Rho-kinase activity in depolarization- and agonist-induced force generation in chicken embryo femoral arteries.
Zoer
Bea
B
Department of Pediatrics, Maastricht University Medical Centre, School for Oncology and Developmental Biology (GROW), P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
Blanco
Carlos E
CE
Villamor
Eduardo
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001835:Body Weight; D002118:Calcium / Q000172:deficiency; D002642:Chick Embryo; D004533:Egtazic Acid / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D053119:Benzophenanthridines; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; C431085:hydroxyfasudil; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D004533:Egtazic Acid; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C016299:chelerythrine; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester