title: Retina derived relaxation is mediated by K(ir) channels and the inhibition of Ca(2+) sensitization in isolated bovine retinal arteries.
abstract: Retinal relaxing factor (RRF) has recently been identified as a novel paracrine regulator of retinal circulation acting differently from well known mediators of the endothelium and the retina. Herein, we aimed to characterize the relaxing mechanism of the retina, i.e. RRF, by evaluating the role of Ca(+2)-dependent and -independent signaling mechanisms as well as inward rectifier K(+) (Kir) channels. Retinal relaxation was determined by placing a piece of retinal tissue just on top of the precontracted bovine retinal arteries mounted in a wire myograph. The retina produced a complete relaxation response, which display a biphasic character, in depolarized arteries contracted by L-type Ca(2+) channel agonist, Bay k 8644. Blockade of L-type Ca(2+) channel by nifedipine, inhibition of sarcoplasmic reticulum Ca(2+)-ATPase by cyclopiazonic acid or removal of extracellular Ca(2+) did not influence the prominent relaxation to the retina. Originally, retinal relaxation was found to be unaffected from the inhibition of myosin light chain kinase by ML7, whereas, completely abolished in the presence of myosin light chain phosphatase (MLCP) inhibitor, Calyculin A. Moreover, the inhibition of Rho kinase by its putative inhibitor, Y-27632 displayed comparable relaxant effects to RRF in retinal arteries precontracted either by prostaglandin F2α or K(+), and augmented the moderate response to the retina in K(+) precontracted arteries. In addition, retinal relaxation was significantly inhibited and lost its biphasic character in the presence of Kir channel blocker, Ba(2+). Our results suggested that inhibition of Ca(2+) sensitization through the activation of MLCP, possibly via interfering with Rho kinase, and the opening of Kir channels are likely to be involved in the inhibitory influence of RRF on the retinal arteries.
authors: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Beyazıt, Istanbul, Turkey.
authors: Selçuk
authors: S
authors: Takır
authors: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Beyazıt, Istanbul, Turkey. Electronic address: sonmezuydesdogan@gmail.com.
authors: B Sönmez
authors: BS
authors: Uydeş-Doğan
authors: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Beyazıt, Istanbul, Turkey; Department of Pharmacology, Faculty of Health Sciences, Cyprus International University, Haspolat, Lefkoşa, North Cyprus, Cyprus.
authors: Osman
authors: O
authors: Özdemir
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D023421:Models, Animal; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D054460:rho-Associated Kinases
keywords: Ca(2+) sensitization; K(ir) channels; Retinal artery; Retinal relaxing factor (RRF); Rho kinase