Acetylcholine-induced vasodilation in the perfused kidney of the streptozotocin-induced diabetic rat: role of prostacyclin.
Using the perfused kidneys of age-matched controls and streptozotocin (STZ)-induced diabetic rats, we previously demonstrated that endothelial dysfunction is present in STZ-induced diabetic rats and that acetylcholine (ACh) increases the level of 6-keto-prostaglandin F(1 alpha) (a metabolite of prostacyclin) in the effluent from such perfused kidneys. Here, we investigated whether the ACh-induced relaxation in the perfused kidney is modulated by prostacyclin and/or thromboxane A(2) (TXA(2)) in the STZ-induced diabetic state. ACh-induced renal vasodilatation was significantly weaker in STZ-induced diabetic rats than in age-matched controls, and it was not affected by treatment with 10 microM furegrelate (TXA(2) -synthase inhibitor) or 1 microM SQ29548 (TXA(2) -receptor antagonist) in either group. However, it was attenuated by 10 microM tranylcypromine (prostacyclin-synthesis inhibitor), but only in the diabetic group. These results suggest that the endothelium-dependent relaxation induced by ACh in the renal vascular bed of STZ-induced diabetic rats is regulated by prostacyclin, not by TXA(2). Increased prostacyclin-signaling may occur to help compensate for the impaired endothelial function seen in the kidney in long-term diabetic states.
Kamata
Katsuo
K
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. kamata@hoshi.ac.jp
Hosokawa
Masao
M
Matsumoto
Takayuki
T
Kobayashi
Tsuneo
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D011464:Epoprostenol / Q000502:physiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D045462:Endothelium-Dependent Relaxing Factors; D014665:Vasodilator Agents; D013311:Streptozocin; D011464:Epoprostenol; D000109:Acetylcholine