Abstract
Purpose:
The carbonic anhydrase inhibitor dorzolamide has been shown to induce relaxation of retinal arterioles and to increase blood flow and oxygenation in the retina. The relaxation effect has been shown to be independent of extracellular pH and CO2, whereas the role of intracellular pH and nitric oxide (NO) for the effect of dorzolamide is unknown.
Methods:
Porcine retinal arterioles were mounted in a myograph and dorzolamide induced relaxation was studied after 1) the addition of the NO synthesis antagonists L-NAME (3x10-4 M) or ODQ (3x10-6 M), and 2) after loading of cells with the pH sensitive fluorophore SNARF-1-AM and studying changes in vascular tone and intracellular fluorescence after the induction of hypoxia, addition of lactate, and intracellular acidification with and without the presence of dorzolamide.
Results:
Dorzolamide significantly reduced the tone of retinal arterioles in the presence of perivascular tissue (p<0.01) which could be significantly reduced by NO antagonists (p<0.05). Dorzolamide also increased intracellular acidification (p<0.03), but changes in vascular tone were not directly linked to intracellular acidosis.
Conclusions:
Dorzolamide-induced vasorelaxation is independent of acidification in the extracellular and the intracellular space, but involves NO and other factors.
Keywords: 443 carbonic anhydrase •
688 retina •
436 blood supply