title: The role of calcium entry on the relaxation response of rho-kinase inhibitor in rabbit renal artery.
abstract: This study was performed to clarify the role of extracellular and intracellular Ca2+ on rho-kinase enzyme inhibition-induced relaxation in rabbit renal arteries. The response to rho-kinase inhibitor (Y-27632) was studied in isolated renal artery segments precontracted with phenylephrine in the presence of voltage-gated calcium channel blocker nifedipine and in the absence of intracellular or extracellular Ca2+. Cumulative addition of rho-kinase inhibitor Y-27632 (10-8-10-5 M) produced a concentration-dependent relaxation in renal artery rings precontracted with phenylephrine. Preincubation with nifedipine (1µM) resulted in a significant increase in relaxation response to rho-kinase inhibitor Y-27632 compared with preincubation with DMSO; the solvent of nifedipine. The maximal relaxation to Y-27632 in renal arteries precontracted with phenylephrine was significantly increased in the Ca-free Krebs containing 100 μmol/l ethylene glycol tetraacetic acid (EGTA) but after depletion of intracellular stores with 20 mmol/l caffeine and 1mmol/l EGTA in Ca2+ free Krebs there was no significant difference between the relaxation to Y-27632 from control response in 2.5 mmol/l Ca2+ Krebs in the renal artery. These results suggest the involvement of extracellular Ca and L-type voltage-operated Ca2+ channels in phenylephrine-induced rho-kinase activation (Fig. 3, Ref. 20).
authors.affiliation: Department of Pharmacology, Necmettin Erbakan University, Konya, Turkey.
authors.forename: B C
authors.initials: BC
authors.lastname: Soner
authors.forename: N
authors.initials: N
authors.lastname: Murat
authors.forename: H
authors.initials: H
authors.lastname: Guven
authors.forename: S
authors.initials: S
authors.lastname: Gidener
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D002118:Calcium