Role of carnitine in regulation of hypoglycemia-induced hypertension and cardiac hypertrophy

Abstract Background: Cardiovascular disease is a leading cause of death in diabetic patients. Hyperglycemia and iatrogenic hypoglycemia exacerbate several pathogenic mechanisms underlying hypertension and heart diseases. Carnitine is a potent endogenous antioxidant and cellular fatty acid transporter for antioxidative stress and energy production in the cardiovascular system. In the present study, we aimed to find the role of carnitine in the regulation of hypoglycemia-induced hypertension and cardiac hypertrophy. Methods: Albino Wistar male rats were divided into six groups. The, first three groups received saline (n= 5), D-carnitine (n= 5) at dose of 500mg/kg/day, intraperitoneal for carnitine depletion, or acetyl-L-carnitine (n= 5) at a dose of 300mg/kg/day, intraperitoneal for carnitine supplementation for 15 days. In the last three groups, rats had pretreatment conditions for 5 days with saline, D-carnitine or acetyl-L-carnitine. Then, they were treated with insulin glargine (InG) for 10 days with saline (n= 6), D-carnitine (n= 5) or acetyl-L-carnitine (n= 6), respectively. Results: Our results showed that carnitine deficiency provoked hypoglycemia-induced hypertension. Mean arterial pressure was elevated from 78.16 ± 4.67 to 100 ± 2.09 mmHg in InG treated group, and from 78.2 ± 3.8 to 123.4 ± 12.6 mmHg in InG+D-carnitine treated group. Acetyl-L-carnitine resisted the elevation in blood pressure in all hypoglycemic animals and kept it within the normal values (68.33 ± 6.7 mmHg). In heart, acetyl-L-carnitine increased myocardial carnitine content leading to the attenuation of hypoglycemia-induced oxidative stress, which was evaluated through measurement of the oxidative stress biomarkers such as inducible nitric oxide synthase, NAD(P)H quinone dehydrogenase-1, heme oxygenase-I, and glutathione transferase. Moreover, acetyl-L-carnitine prevented induction of cardiac hypertrophy during hypoglycemic conditions, which was assessed via the evaluation of mRNA expression of the cardiac hypertrophy biomarkers, α-myosin heavy chain and β-myosin heavy chain. Conclusions: These findings demonstrate that carnitine plays an essential role in providing energy and antioxidants to the cardiovascular system leading to the prevention of hypoglycemia-induced hypertension and cardiac hypertrophy.