Hypoxia-induced relaxation of porcine retinal arterioles in vitro depends on inducible NO synthase and EP4 receptor stimulation in the perivascular retina.

Abstract

PURPOSE:

Hypoxia-induced relaxation of porcine retinal arterioles has been shown to be reduced during inhibition of prostaglandin synthesis and nitric oxide synthase (NOS). The purpose of this study was to identity the specific prostaglandin receptor(s) and source(s) of NO mediating this effect.

METHODS:

Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph and were exposed to hypoxia in the presence of one of the following: the general NO synthase inhibitor L-NAME, the selective iNOS inhibitor 1400W, the selective nNOS inhibitor 7-nitroindazole, the general cyclooxygenase (COX) inhibitor ibuprofen or an antagonist to the FP- (AL 8810), DP- (BWA868C), EP1 - (SC-19220), EP2 - (PF-044189) or EP4 receptors (GW627368X). The experiments were repeated after removal of the perivascular retinal tissue.

RESULTS:

Hypoxia induced relaxation of retinal arterioles with preserved perivascular retinal tissue. This relaxation was significantly reduced in the presence of L-NAME, 1400W, ibuprofen and the EP4 receptor antagonist GW627368X. The simultaneous addition of L-NAME or 1400W in combination with ibuprofen, but not GW627368X, reduced hypoxia-induced vasorelaxation additively as compared to the effect of the compounds individually.

CONCLUSION:

Hypoxia-induced vasorelaxation of porcine retinal arterioles is mediated by inducible NOS and stimulation of EP4 receptors acting through separate pathways, but mechanisms unrelated to the studied prostaglandin receptors and NOS products are also involved.

• Authors: Pernille Oversø Hansen, Sidse Kringelholt, Ulf Simonsen, Toke Bek
• Journal: Acta ophthalmologica (Acta Ophthalmol) Vol. 93 Issue 5 Pg. 457-463 (Aug 2015) ISSN: 1755-3768 [Electronic] England
• PMID: 25619924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Chemical References

• Cyclooxygenase Inhibitors
• Enzyme Inhibitors
• Receptors, Prostaglandin E, EP4 Subtype
• Nitric Oxide Synthase Type II

Topics

• Animals
• Arterioles (physiology)
• Cyclooxygenase Inhibitors (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Female
• Hydrogen-Ion Concentration
• Hypoxia (metabolism)
• Male
• Muscle Relaxation (physiology)
• Muscle, Smooth, Vascular (physiology)
• Myography
• Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
• Receptors, Prostaglandin E, EP4 Subtype (agonists, antagonists & inhibitors, metabolism)
• Retinal Artery (physiology)
• Sus scrofa