Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats.
We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treatment with STZ or the vehicle. The fundus images were captured with the digital fundus camera system for small animals we developed and diameters of retinal blood vessels contained in the digital images were measured. Epinephrine increased the diameters of retinal blood vessels, but the vasodilator responses were reduced in diabetic rats. Dopamine produced a biphasic retinal vascular response with an initial vasoconstriction followed by a vasodilation. The vasoconstrictor effects of dopamine on retinal arterioles were enhanced in diabetic rats, whereas the difference between the two groups was abolished by treatment with propranolol. The vasodilator effect of isoproterenol, but not of the activator of adenylyl cyclase colforsin, on retinal blood vessels was reduced in diabetic rats. No difference in vasoconstriction of retinal blood vessels to phenylephrine between non-diabetic and diabetic rats was observed. The vasodilator responses of retinal blood vessels to 1,1-dimethyl-4-phenylpiperazinium, a ganglionic nicotinic receptor agonist, were also attenuated in diabetic rats. These results suggest that diabetes mellitus alters the retinal vascular responses to circulating catecholamines and the impairment of vasodilator responses mediated by beta-adrenoceptors contributes to the alteration.
Nakazawa
Taisuke
T
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Sato
Ayumi
A
Mori
Asami
A
Saito
Maki
M
Sakamoto
Kenji
K
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010781:Photography / Q000295:instrumentation; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; C122001:colforsin daropate; D005576:Colforsin; D010656:Phenylephrine; D004246:Dimethylphenylpiperazinium Iodide; D013311:Streptozocin; D011433:Propranolol; D007545:Isoproterenol; D004298:Dopamine; D004837:Epinephrine