15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and dorzolamide

Carbonic anhydrase inhibitors reduce intraocular pressure, which may protect the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to dilate the blood vessels in the retina and the optic nerve head. The purpose of the present study was to investigate whether CO(2), H(+), or factors other than carbonic anhydrase inhibition are involved in this vasodilating effect.. Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric force measurements. After precontraction with the prostaglandin analogue U46619, concentration-response experiments were performed with acetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were performed at normal pH and during acidosis, during normocapnia and hypercapnia, as well as in the nominal absence of CO(2) and HCO(3)(-).. The maximum relaxation was significantly lower and the EC(50) significantly higher during normal pH compared with acidosis (P = 0.002 and P < 0.0001, respectively), but neither the maximum relaxation nor EC(50) was changed by hypercapnia (P = 0.054 and P = 0.57, respectively). The findings confirmed that carbonic anhydrase-induced vasodilation depends on the perivascular retinal tissue and that dorzolamide produces significantly more pronounced relaxation than does acetazolamide. EC(50) of carbonic anhydrase inhibitor-induced vasorelaxation and the maximum relaxation of dorzolamide were unchanged in the nominal absence of CO(2) and HCO(3)(-) (P = 0.65 and P < 0.0001, respectively).. The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal arterioles depends on the perivascular retinal tissue and acidosis, but not on hypercapnia. The effect involves mechanisms other than carbonic anhydrase inhibition.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetazolamide; Acidosis; Animals; Arterioles; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Dose-Response Relationship, Drug; Hydrogen-Ion Concentration; Hypercapnia; Muscle, Smooth, Vascular; Myography; Nifedipine; Retinal Artery; Sulfonamides; Swine; Thiophenes; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Inhibition of carbonic anhydrase in the eye is an important treatment modality for reducing the intraocular pressure in glaucoma. However, evidence suggests that carbonic anhydrase inhibition also exerts a relaxing effect on the vessels in the optic nerve, and it has been suggested that this vasorelaxing effect is a result of an interplay between the perivascular tissue and constituents in the retinal vascular wall. However, the exact nature of this interplay is unknown.. Isolated porcine retinal arterioles and arterioles with preserved perivascular retinal tissue were mounted in a myograph. After precontraction with the prostaglandin analogue U46619, the vasorelaxing effect of the carbonic anhydrase inhibitors methyl bromopyruvate, ethyl bromopyruvate, acetazolamide, and dorzolamide were studied.. All the examined carbonic anhydrase inhibitors induced a significant relaxation of retinal arterioles. There was no significant difference between the effect of the different carbonic anhydrase inhibitors in the presence of perivascular retinal tissue. However, in the isolated retinal arterioles the vasodilating effect of dorzolamide was significantly lower, and the vasodilating effect of acetazolamide almost disappeared.. A further elucidation of the mechanisms of action of carbonic anhydrase-induced dilation of retinal arterioles may contribute to a better understanding of the regulation of retinal blood flow. The perivascular retinal tissue may play a significant role in diameter control of retinal arterioles.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetazolamide; Animals; Arterioles; Carbonic Anhydrase Inhibitors; Muscle, Smooth, Vascular; Myography; Retinal Artery; Sulfonamides; Swine; Thiophenes; Vasoconstrictor Agents; Vasodilation