Increased vasoconstriction to noradrenaline by 1400W, inhibitor of iNOS, in rats with streptozotocin-induced diabetes.
There is evidence that inducible nitric oxide synthase (iNOS) is activated at the acute phase of diabetes. We examined if selective inhibition of iNOS by 1400W (N-3-aminomethyl-benzyl-acetamidine) increases vascular response to noradrenaline in rats with streptozotocin (60 mg/kg i.v.)-induced diabetes for a duration of 3 weeks. The effects of noradrenaline on mean arterial pressure (MAP; 6, 16, 45 and 122x10(-9) mol/kg/min) and mean circulatory filling pressure (MCFP; 16 and 45x10(-9) mol/kg/min) were obtained in conscious and unrestrained diabetic rats and control rats before as well as after treatment with 1400W (3 mg/kg followed by 3 mg/kg/h, i.v.). Rats with early streptozotocin-induced diabetes had decreased mean arterial pressure and mean circulatory filling pressure responses to noradrenaline. Treatment with 1400W did not affect responses in the control rats but increased maximum pressor response to noradrenaline (from 46+/-3 to 63+/-5) and mean circulatory filling pressure response to the high dose (45 nmol/kg/min) of noradrenaline (from 1.0+/-0.2 to 3.8+/-0.3 mmHg) in the diabetic rats. Thus, selective inhibition of iNOS by 1400W increases arterial and venous constriction to noradrenaline in conscious rats with streptozotocin-induced diabetes.
Cheng
Xing
X
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Pang
Catherine C Y
CC
D000578:Amidines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D009638:Norepinephrine