Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat.
Recently we showed that the administration of intraperitoneal L-carnitine (CA) has insulin-sensitizing effects in the high fructose-fed Wistar rat, a widely used model of metabolic syndrome. The present study was conducted to examine the regulatory effects of CA on blood pressure (BP) and related pressor mechanisms. Fructose-fed rats (FFR) showed elevated BP, cardiac hypertrophy, glucose intolerance, and increases in plasma glucose, insulin, free fatty acids (FFA), and angiotensin-converting enzyme (ACE) activity. They also showed increased protein kinase C betaII (PKC betaII) expression and oxidative stress in cardiac tissue. In plasma, decreased kallikrein enzyme activity and nitric oxide metabolites were observed, compared to control. Simultaneous treatment with CA (300 mg/Kg) mitigated these alterations. PKC betaII expression was similar to that of control; the rats displayed normal BP and ACE activity, enhanced antioxidant protection, and close to normal values of metabolic parameters. The BP-lowering effect of CA was abolished when CA-treated rats were administered L-nitroarginyl methyl ester (L-NAME 6g/Kg). These observations suggest that the BP-lowering action of CA in this model could be attributed to multiple and interrelated mechanisms, such as an increase in NO and kinin availability, reduction in PKC action, and antioxidant protection.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, India.
P
P
Rajasekar
N
N
Palanisamy
C V
CV
Anuradha
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002331:Carnitine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy; D009569:Nitric Oxide / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051381:Rats; D017208:Rats, Wistar; D014803:Vitamin B Complex / Q000494:pharmacology*
D014803:Vitamin B Complex; D009569:Nitric Oxide; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D007703:Peptidyl-Dipeptidase A; D002331:Carnitine