Effect of pioglitazone on L-NAME induced hypertension in diabetic rats.
The present study investigates the effect of pioglitazone treatment on blood pressure, vascular reactivity and antioxidant enzymes in L-NAME induced hypertension in normal and STZ-diabetic rats. Diabetes was induced in male Sprague Dawley rats (200+/-15 g) by single intravenous injection of 55 mg/kg of streptozotocin (STZ). Rats were randomized into diabetic and nondiabetic groups, Nomega-nitro-L-arginine-methyl ester (L-NAME, 50 mg/kg) was administered in drinking water for 4 weeks. They were treated with pioglitazone (10 mg/kg/day, p.o.) for 4 weeks and following protocol was carried out. Blood pressure, blood glucose levels and body weight were measured. Thoracic aorta was isolated and dose response curve of phenylephrine (PE) with intact and denuded endothelium was recorded. Dose response curve of acetylcholine (Ach) and sodium nitroprusside (SNP) was recorded in precontracted rings. Lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione were estimated in liver, kidney, and aorta. Pioglitazone produced no significant effect on blood glucose levels, body weight and blood pressure of L-NAME administered nondiabetic and diabetic rats. Pioglitazone treatment had no significant effect on PE induced contraction and Ach induced relaxation in L-NAME diabetic and nondiabetic rats. SNP completely relaxed aortic rings of all the groups. Higher oxidative stress in case of diabetic rats was significantly (p<0.05) reduced by pioglitazone treatment. Although pioglitazone reduced oxidative stress in diabetic rats, there was no significant effect on blood pressure as there was complete absence of nitric oxide due to administration of L-NAME. Hence from the present study it can be concluded that reduction in blood pressure in case of STZ-diabetic rats is nitric oxide mediated.
Majithiya
Jayesh B
JB
Pharmacy Department, Faculty of Technology and Engineering, M. S. University of Baroda, Kalabhavan, Baroda 390001, Gujarat, India. jayeshbm@yahoo.com
Parmar
Arvind N
AN
Trivedi
Chitrang J
CJ
Balaraman
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002374:Catalase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone