BACKGROUND/AIMS: Endothelial cell dysfunction in the ocular circulation may contribute to normal pressure glaucoma (NPG). This study aimed to investigate the contributions made by endothelium derived relaxing factors to relaxation of (1) subcutaneous resistance arteries from patients with NPG, and (2) porcine ciliary arteries. METHODS: Human gluteal resistance arteries were isolated from seven patients with NPG and matched controls. Human and porcine arteries produced endothelium dependent relaxation when exposed to acetylcholine (ACh) (10(-9)-3 x 10(-5)M) or bradykinin (10(-10)-3 x 10(-6)M). Pharmacological agents were used to inhibit the nitric oxide pathway (l-arginine analogues, soluble guanylate cyclase inhibitor), endothelium derived hyperpolarising factor (EDHF) activity (potassium channel antagonists), and prostaglandin synthesis (cyclo-oxygenase inhibitors). RESULTS: In all arteries, endothelium dependent relaxation was attenuated by nitric oxide (NO) inhibition or potassium channel blockade, but not by cyclo-oxygenase inhibition. Inhibition of ACh mediated relaxation by potassium channel antagonists was greater (p<0.05) in patients with NPG (Emax, 55.4% (SD 8.16%) relaxation, n = 4) than controls (Emax, 81.8% (6.0%), n = 5). In contrast, combined inhibition of NO synthase (NOS) and cyclo-oxygenase produced similar inhibition of ACh mediated relaxation in both groups. CONCLUSIONS: The enhanced contribution of EDHF to ACh mediated relaxation in systemic resistance arteries from NPG patients may contribute to the maintained endothelium mediated relaxation in these vessels. EDHF also contributes significantly to bradykinin mediated relaxation in porcine ocular ciliary arteries. Therefore, similar changes in the balance of relaxing factors in the ocular circulation could influence the response of the eye to vascular endothelial dysfunction in NPG.
BACKGROUND/AIMS: Endothelial cell dysfunction in the ocular circulation may contribute to normal pressure glaucoma (NPG). This study aimed to investigate the contributions made by endothelium derived relaxing factors to relaxation of (1) subcutaneous resistance arteries from patients with NPG, and (2) porcine ciliary arteries. METHODS:Human gluteal resistance arteries were isolated from seven patients with NPG and matched controls. Human and porcine arteries produced endothelium dependent relaxation when exposed to acetylcholine (ACh) (10(-9)-3 x 10(-5)M) or bradykinin (10(-10)-3 x 10(-6)M). Pharmacological agents were used to inhibit the nitric oxide pathway (l-arginine analogues, soluble guanylate cyclase inhibitor), endothelium derived hyperpolarising factor (EDHF) activity (potassium channel antagonists), and prostaglandin synthesis (cyclo-oxygenase inhibitors). RESULTS: In all arteries, endothelium dependent relaxation was attenuated by nitric oxide (NO) inhibition or potassium channel blockade, but not by cyclo-oxygenase inhibition. Inhibition of ACh mediated relaxation by potassium channel antagonists was greater (p<0.05) in patients with NPG (Emax, 55.4% (SD 8.16%) relaxation, n = 4) than controls (Emax, 81.8% (6.0%), n = 5). In contrast, combined inhibition of NO synthase (NOS) and cyclo-oxygenase produced similar inhibition of ACh mediated relaxation in both groups. CONCLUSIONS: The enhanced contribution of EDHF to ACh mediated relaxation in systemic resistance arteries from NPG patients may contribute to the maintained endothelium mediated relaxation in these vessels. EDHF also contributes significantly to bradykinin mediated relaxation in porcine ocular ciliary arteries. Therefore, similar changes in the balance of relaxing factors in the ocular circulation could influence the response of the eye to vascular endothelial dysfunction in NPG.
Authors: R P Brandes; A Behra; C Lebherz; R H Böger; S M Bode-Böger; L Phivthong-Ngam; A Mügge Journal: Atherosclerosis Date: 1997-11 Impact factor: 5.162
Authors: H Shimokawa; H Yasutake; K Fujii; M K Owada; R Nakaike; Y Fukumoto; T Takayanagi; T Nagao; K Egashira; M Fujishima; A Takeshita Journal: J Cardiovasc Pharmacol Date: 1996-11 Impact factor: 3.105
Authors: Joanna Wierzbowska; Stanisław Wojtkiewicz; Anna Zbieć; Robert Wierzbowski; Adam Liebert; Roman Maniewski Journal: Med Sci Monit Date: 2014-12-11