title: Altered vasoactivity in the early diabetic eye: measured in the isolated perfused rat eye.
abstract: The effect of 4 weeks streptozotocin-induced diabetes on ocular vascular resistance responses to noradrenalin (NA), adrenalin (A), phenylephrine (PHE), isoproterenol (ISOP), prostaglandin F2 alpha (PGF2 alpha). 5-hydroxytryptamine (5-HT) and angiotensin II (ANG II), was determined using a newly-developed, isolated, arterially-perfused rat eye preparation, by comparing responses from control and diabetic eyes. After extensive preliminary experiments to establish optimum parameters, the ophthalmic artery of enucleated control and diabetic rat eyes was cannulated and the retinal and uveal vasculature perfused at a constant flow with Na(+)-Krebs solution after streptozotocin-induced diabetes had been established for 4 weeks. The eyes were maintained in an environment-controlled organ bath. Perfusion pressure was monitored as increasing log M concentrations of agonists were added to the perfusate. Total ocular resistance could be calculated from knowledge of flow and pressure. In control eyes, NA, A, PHE, PGF2 alpha, and 5-HT all produced dose-dependent increases in total vascular resistance, with the following order of potency: NA = A > 5-HT > PHE = PGF2 alpha at 10(-4) M. The ocular circulation was not sensitive to isoproterenol and angiotensin II. In diabetic eyes responses to NA, A, PGF2 alpha and 5-HT were altered. Diabetic responses to NA and A had lower thresholds with larger resistance increases at low concentrations. However, the rate of increase in resistance with concentration was more gradual in diabetic eyes so that at 10(-4) M control responses were larger. Diabetic resistance responses to PGF2 alpha had the same threshold as in control eyes, but were greater in magnitude with an earlier peak at 10(-4) M. In contrast diabetic resistance responses to 5-HT were reduced, peaked at a lower resistance at 10(-4) M, but had the same threshold as those in the control eye. Basal vascular resistances in control: 3.14 +/- 0.32 mmHg min microliter-1 (n = 28), and diabetic eyes: 3.44 +/- 0.19, mmHg min microliter-1 (n = 36), were not significantly different. Vasoactivity in the early diabetic eye is disturbed with the effective balance between different agonists altered in favour of catecholamines at physiological concentrations. This may be related to the early changes in blood flow and oxygen distribution already reported in the rat eye, as well as changes to autonomic function. The isolated perfused rat eye is a valuable technique for investigating such vascular reactivity in animal models of retinal disease.
authors.affiliation: Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands.
authors.forename: E N
authors.initials: EN
authors.lastname: Su
authors.forename: D Y
authors.initials: DY
authors.lastname: Yu
authors.forename: V A
authors.initials: VA
authors.lastname: Alder
authors.forename: P K
authors.initials: PK
authors.lastname: Yu
authors.forename: S J
authors.initials: SJ
authors.lastname: Cringle
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D005123:Eye / Q000098:blood supply*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009900:Optic Nerve / Q000098:blood supply; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D012701:Serotonin; D015237:Dinoprost; D007545:Isoproterenol