Constriction of retinal arterioles to endothelin-1: requisite role of rho kinase independent of protein kinase C and L-type calcium channels. Academic Article uri icon


  • PURPOSE: Although endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in several retinal pathologies, the underlying mechanism of vasoconstriction is understood incompletely. We addressed this issue by assessing the contributions of extracellular calcium (Ca), L-type voltage-operated calcium channels (L-VOCCs), Rho kinase (ROCK), and protein kinase C (PKC) to ET-1-induced constriction of porcine retinal arterioles, all of which have been implicated commonly in vascular smooth muscle contraction. METHODS: Porcine retinal arterioles (~50-100 m) were isolated for vasomotor study and molecular assessment of ROCK isoforms. RESULTS: Isolated arterioles developed stable basal tone at 55 cmHO luminal pressure and constricted to ET-1 (0.1 nM) with a 40 6% reduction in resting diameter in 20 minutes. In the absence of extraluminal Ca, arterioles lost basal tone and failed to constrict to ET-1. Although L-VOCC inhibitor nifedipine reduced basal tone and blocked vasoconstriction to PKC activator PDBu, vasoconstriction to ET-1 was unaffected. The broad-spectrum PKC inhibitor G-6983 abolished vasoconstriction to PDBu, but did not alter ET-1-induced vasoconstriction or basal tone. Incubation of arterioles with ROCK inhibitor H-1152 abolished basal tone and vasoconstrictions to ET-1 and PDBu. Both ROCK1 and ROCK2 isoforms were expressed in the retinal arteriolar wall. CONCLUSIONS: Extracellular Ca entry via L-VOCCs and basal ROCK activity play important roles in the maintenance of basal tones of porcine retinal arterioles. ET-1-induced constriction is mediated by extracellular Ca entry independent of L-VOCCs and by ROCK activation without the involvement of PKC. However, direct PKC activation can cause vasoconstriction via L-VOCC and ROCK signaling.

published proceedings

  • Invest Ophthalmol Vis Sci

author list (cited authors)

  • Potts, L. B., Ren, Y. i., Lu, G., Kuo, E., Ngo, E., Kuo, L., & Hein, T. W.

citation count

  • 26

complete list of authors

  • Potts, Luke B||Ren, Yi||Lu, Guangrong||Kuo, Enoch||Ngo, Ellen||Kuo, Lih||Hein, Travis W

publication date

  • January 2012