Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2025
Relaxation of Precontracted Ciliary Artery and Ciliary Muscle In Vitro by Kinin Peptides: Relevance to Retinal Blood Flow and Intraocular Pressure Regulation.
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Sharif Najam A, Kulkarni-Chitnis Madhura, Okolie Anthonia, Chaudhry Saima D, Njie-Mbye Ya Fatou, Ohia Sunny E
Аннотация
PURPOSE: To study the ability of five kinin peptides to relax phenylephrine-contracted bovine posterior ciliary artery (PCA; major retinal blood supplier) and carbachol-contracted ciliary muscle (CM) (involved in accommodation and aqueous humor drainage) in vitro.
METHODS: Isolated bovine CM strips and PCA rings were mounted in small organ baths and perfused with oxygenated Krebs' solution containing 3 µM flurbiprofen. The tissues were then contracted with 10 µM carbachol (for CM) and 10 µM phenylephrine (for PCA), and the relaxant effects of kinins (0.3 nM to 10 µM) were determined.
RESULTS: All tested kinin peptides concentration-dependently relaxed precontracted CM and PCA in a biphasic manner. The concentrations of the peptides (BK [bradykinin], Hyp3-BK, Lys-BK, Met-Lys-BK, and Des-Arg9-BK) yielding half-maximal relaxation (EC50) of PCA via the high potency receptor site ranged between 0.1 nM and 9.0 nM (n = 5-6). Precontracted PCA relaxation by the same kinins via the low potency receptor site occurred with EC50 values of 39.5-399 nM (n = 5-6). In contrast, EC50 values for these peptides relaxing the precontracted CM strips were 0.25-30 nM (high potency receptor site) and 100-3,000 nM (low potency receptor site) (n = 3-6). Precontracted PCA rings were significantly (generally P < 0.005-0.05) more sensitive to the relaxant activity of the kinin peptides than precontracted CM strips.
CONCLUSIONS: The tissue relaxant agonist profile of the kinins in both precontracted CM strips and PCA rings, as judged by the 2-site-fit data, indicated the involvement of both B1- and B2-receptor subtypes.
METHODS: Isolated bovine CM strips and PCA rings were mounted in small organ baths and perfused with oxygenated Krebs' solution containing 3 µM flurbiprofen. The tissues were then contracted with 10 µM carbachol (for CM) and 10 µM phenylephrine (for PCA), and the relaxant effects of kinins (0.3 nM to 10 µM) were determined.
RESULTS: All tested kinin peptides concentration-dependently relaxed precontracted CM and PCA in a biphasic manner. The concentrations of the peptides (BK [bradykinin], Hyp3-BK, Lys-BK, Met-Lys-BK, and Des-Arg9-BK) yielding half-maximal relaxation (EC50) of PCA via the high potency receptor site ranged between 0.1 nM and 9.0 nM (n = 5-6). Precontracted PCA relaxation by the same kinins via the low potency receptor site occurred with EC50 values of 39.5-399 nM (n = 5-6). In contrast, EC50 values for these peptides relaxing the precontracted CM strips were 0.25-30 nM (high potency receptor site) and 100-3,000 nM (low potency receptor site) (n = 3-6). Precontracted PCA rings were significantly (generally P < 0.005-0.05) more sensitive to the relaxant activity of the kinin peptides than precontracted CM strips.
CONCLUSIONS: The tissue relaxant agonist profile of the kinins in both precontracted CM strips and PCA rings, as judged by the 2-site-fit data, indicated the involvement of both B1- and B2-receptor subtypes.