Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery

The vascular endothelial cells have the ability to modulate local vascular tone by releasing relaxing factors such as nitric oxide or the vasoconstrictor peptide endothelin-1. Although this regulatory system is found in all vertebrates, there is a great heterogeneity in the release of these endothelium-derived substances, from one organ to an other, between large and small vessels, and between different species. Therefore, observations made in certain vascular beds or animals do not necessarily apply to human ophthalmic circulation. The present study was designed to investigate endothelial mediators in the human ophthalmic artery. The results show that in the human ophthalmic artery, nitric oxide is released under basal conditions and that its production can be markedly stimulated by bradykinin, acetylcholine, and particularly histamine, which cause profound vascular relaxation. In contrast, endothelin-1 evoked potent contractions, which were unaffected by the calcium antagonist nifedipine. However, upon re-exposure of the blood vessels to the peptide, marked tachyphylaxis occurred. These findings demonstrate that in the human ophthalmic artery, endothelium-derived nitric oxide and endothelin are very potent modulators of vascular tone, suggesting that they play an important role in the regulation of local blood flow in the eye. Hence, endothelium dysfunction may represent a new pathogenetic mechanism in disease states associated with altered blood flow to the eye, such as diabetes, hypertension, and some forms of low-tension glaucoma.