Chronic treatment with losartan (angiotensin II type 1 receptor antagonist) normalizes enhanced acetylcholine-induced coronary vasoconstriction in isolated perfused hearts of type 2 diabetic OLETF rats.
We previously reported that isolated perfused hearts from streptozotocin (STZ)-induced diabetic rats exhibited increases in the sensitivity of the coronary vasoconstriction induced by acetylcholine (ACh) infusion (versus age-matched controls) (Kamata et al., 2008). Here, we examined the ACh-induced coronary vasoconstriction in perfused hearts taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, at the chronic stage of diabetes (38-40 weeks old). The ACh-induced vasoconstriction was greatly enhanced in such rats [versus age-matched control Long-Evans Tokushima Otsuka (LETO) rats]. This enhancement was improved by the chronic administration of the angiotensin II type I receptor (AT(1)-receptor) antagonist losartan (25 mg kg(-1), p.o., for 4 weeks). Further, the enhancement of the ACh-induced vasoconstriction seen in the OLETF group was suppressed by tempol, a superoxide dismutase mimetic. These results suggest that the coronary artery contractile response to ACh is enhanced in type 2 diabetic OLETF rats, and that this enhancement may be attributable to increased AT(1) receptor-mediating signaling and/or to increased oxidative stress.
Matsumoto
Takayuki
T
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Ozawa
Yuta
Y
Taguchi
Kumiko
K
Kobayashi
Tsuneo
T
Kamata
Katsuo
K
D000109:Acetylcholine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D013113:Spin Labels; D014661:Vasoconstriction / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D003497:Cyclic N-Oxides; D013113:Spin Labels; D019808:Losartan; D000109:Acetylcholine; C001803:tempol