Vasodilation of retinal arteriole mediated by corticotropin-releasing factor receptor is impaired in streptozotocin-induced diabetic rats.
We investigated the vasodilator responses of retinal arterioles induced by stimulating corticotropin-releasing factor receptors in non-diabetic and diabetic rats. Male Wistar rats were treated with streptozotocin (65 mg/kg, i.v.) and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 mug/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye and infused with a mixture of norepinephrine and epinephrine to maintain adequate systemic circulation under artificial ventilation. Fundus images were captured with an original high-resolution digital fundus camera system. The vasodilator responses of retinal arterioles were assessed by measuring changes in diameters of retinal arterioles in response to urocortin and urocortin 2. Both urocortin (0.03-1.0 micromol/kg, i.v.) and urocortin 2 (0.1-3.0 micromol/kg, i.v.) increased diameters of retinal arterioles and decreased systemic blood pressure in a dose-dependent manner. The responses to urocortins were reduced in diabetic rats. These results suggest that urocortin and urocortin 2 play as vasodilators in retinal and peripheral resistance arterioles. The impairment of vasodilation mediated by the corticotropin-releasing factor receptors may contribute to the alteration of retinal and systemic circulation in the diabetic state.
Kaneko
Yoshiko
Y
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
Saito
Maki
M
Mori
Asami
A
Sakamoto
Kenji
K
Kametaka
Sokichi
S
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D012161:Retinal Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013311:Streptozocin; D054832:Urocortins; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D013311:Streptozocin; D003346:Corticotropin-Releasing Hormone