Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats.
1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.
Kamata
K
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Miyata
N
N
Kasuya
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine