Pharmacological vascular reactivity in isolated diabetic rabbit ciliary artery

• Published in: Experimental eye research 2006-12, Vol.83 (6), p.1317-1324
• Main Authors: Goseki, Toshiaki, Ishikawa, Hitoshi, Nishimoto, Hisaharu, Mashimo, Kimiyo, Uga, Shigekazu, Yoshitomi, Takeshi, Shimizu, Kimiya
• Format: Article
• Language: English
• Subjects: alloxan; Animals; Carbachol - pharmacology; Ciliary Arteries - drug effects; Ciliary Arteries - physiopathology; Ciliary Arteries - ultrastructure; ciliary artery; diabetes mellitus; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetic Angiopathies - pathology; Diabetic Angiopathies - physiopathology; Dose-Response Relationship, Drug; Isotonic Solutions - pharmacology; Microscopy, Electron; ocular circulation; Phenylephrine - pharmacology; Potassium - pharmacology; rabbit; Rabbits; vasoconstriction; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; vasodilatation; Vasodilation - drug effects
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2006.06.001

Impairment of the ocular circulation induced by diabetes mellitus has not been fully defined, but is thought to be related to hemodynamic changes in the ocular circulation. The purpose of the present study is to investigate the functional and morphological changes occurring in the ciliary artery wall of rabbits with alloxan-induced diabetes mellitus. A single intravenous bolus injection of alloxan (100 mg/kg) was given to each of 26 10-week-old rabbits and 16 sham-injected control rabbits. Twenty weeks later, control rabbits and diabetic rabbits were sacrificed, and their ciliary arteries were mounted in a myograph system. The responses of these arteries to high K + solution (K-Krebs solution), phenylephrine and carbachol were investigated using isometric tension recording. L-NAME ( NG-nitro- l-arginine methyl ester; 100 μM) and indomethacin (1 μM) were also used to test the mechanism causing the carbachol induced relaxation. The arteries were also examined morphologically. The maximum tensions induced by K-Krebs solution in this tissue were not significantly different: 17.2 ± 0.8 mN ( n = 16) in the control rabbits and 17.6 ± 0.8 mN ( n = 23) in the diabetic rabbits ( P = 0.36). Phenylephrine caused dose-dependent contraction with EC 50 values of 1.3 ± 0.4 μM ( n = 6) in the control and 5.1 ± 2.3 μM ( n = 6) in the diabetic rabbits, but there was no significant difference between the two ( P = 0.36). Carbachol induced dose-dependent relaxations in segments precontracted with K-Krebs solution. These relaxations were significantly reduced in the diabetic rabbits. The maximum relaxation induced by carbachol was 77.0 ± 2.4% (10 μM) and 66.4 ± 2.5% (100 μM) in the control and diabetic rabbits, respectively. These values were significantly different ( P = 0.0076). The IC 50 value for carbachol was 396.3 ± 58.4 nM ( n = 16) in the control, and 443.6 ± 141.1 nM ( n = 23) in the diabetic rabbit ( P = 0.87). Application of a 100 μM nitric oxide synthase inhibitor, L-NAME, significantly inhibited the amplitude of relaxations evoked by carbachol ( P = 0.0066). However, these relaxations were not inhibited by pretreatment with 1 μM indomethacin ( P = 0.60). Histologically, the frequency of invaginations was less in the diabetic arterioles with a flattening of the lamina in the diabetic rabbits than in the controls. The cytoplasm of endothelial cells contained large vacuoles, indicating weak adhesion to the lamina. Some endothelial cells even showed vacuolar degenerati