Role of carnitine in regulation of blood pressure (MAP/SBP) and gene expression of cardiac hypertrophy markers (α/β‐MHC) during insulin‐induced hypoglycaemia: Role of oxidative stress
Cardiovascular disease is a leading cause of death in diabetic patients. Hyperglycaemia and iatrogenic hypoglycaemia exacerbate several pathogenic mechanisms underlying hypertension and heart diseases. Carnitine is a potent endogenous antioxidant and cellular fatty acid transporter for antioxidative...
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Veröffentlicht in: | Clinical and experimental pharmacology & physiology 2021-04, Vol.48 (4), p.478-489 |
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Zusammenfassung: | Cardiovascular disease is a leading cause of death in diabetic patients. Hyperglycaemia and iatrogenic hypoglycaemia 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. The current study aimed to find the role of carnitine in the regulation of hypoglycaemia‐induced hypertension and cardiac hypertrophy. Male rats received insulin glargine (InG) to induce hypoglycaemia followed by D‐carnitine or acetyl‐L‐carnitine for carnitine depletion or carnitine supplementation, respectively. The obtained results showed that carnitine deficiency provoked hypoglycaemia‐induced hypertension. Mean arterial pressure was elevated from 78.16 ± 11.4 to 100 ± 5.11 mm Hg in InG treated group, and from 78.2 ± 8.5 to 123.4 ± 28.2 mm Hg in InG + D‐carnitine treated group. Acetyl‐L‐carnitine resisted the elevation in blood pressure in all hypoglycaemic animals and kept it within the normal values (68.33 ± 6.7 mm Hg). Acetyl‐L‐carnitine increased myocardial carnitine content leading to the attenuation of hypoglycaemia‐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 S‐transferase. Moreover, acetyl‐L‐carnitine prevented induction of gene expression of cardiac hypertrophy markers during hypoglycaemic conditions, which was assessed via the evaluation of mRNA expression of α‐myosin heavy chain and β‐myosin heavy chain. These findings demonstrate that carnitine might play an essential role in prevention of hypoglycaemia‐induced hypertension and cardiac hypertrophy through providing energy and antioxidants to the cardiovascular system.
The current study investigated the effect of InG‐induced hypoglycaemia on the haemodynamic function and carnitine levels in the heart. The role of carnitine was approved in the prevention of hypoglycaemia‐induced oxidative stress leading to attenuation of the elevated blood pressure and gene expression of cardiac hypertrophy markers. |
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ISSN: | 0305-1870 1440-1681 1440-1681 |
DOI: | 10.1111/1440-1681.13455 |