Constriction of porcine retinal arterioles induced by endothelin-1 and the thromboxane analogue U46619 in vitro decreases with increasing vascular branching level.

PURPOSE: The retinal blood flow depends on the diameter of retinal arterioles, but diameter changes in these vessels have hitherto only been assessed in vessels larger than approximately 100 µm. Therefore, a new method was developed for studying diameter changes along the vascular tree of arterioles in whole perfused segments of porcine retinas, and the effect of known vasoconstrictors on the diameter of retinal arterioles at different branching levels were studied. METHODS: Thirty-four whole-mounted porcine retinas were placed in a specially designed tissue chamber. On the basis of video recordings through an inverted microscope, the diameter of retinal arterioles was measured at five different branching levels before and after addition of a high potassium concentration, or increasing concentrations of endothelin-1, the prostaglandin analogue U46619, noradrenaline or none (time controls). RESULTS: The baseline diameter ranged from 136 µm (95% CI 132-140 µm) for 1st order arterioles to 33 µm (95% CI 21-44 µm) for 5th order arterioles. In 1st order arterioles, endothelin produced 56.6% (95% CI 47.6-64.0) and U46619 14.6% (95% CI 5.7-22.6) relative constriction compared with baseline, which for both compounds decreased significantly with increasing branching level (p<0.0001 and p<0.0001, respectively). The change in diameter during addition of noradrenaline did not differ significantly from the time controls (p=0.07). CONCLUSIONS: The effect of retinal vasoconstrictors differs among larger and smaller arterioles. The study highlights the need for investigating diameter regulation in smaller retinal arterioles as a basis for understanding normal and pathological changes in retinal blood flow.

The vasodilating effect of acetazolamide and dorzolamide involves mechanisms other than carbonic anhydrase inhibition.

PURPOSE: 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. METHODS: 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)(-). RESULTS: 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). CONCLUSIONS: 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.