Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats.
It has been shown that oxidative stress is involved in the pathogenesis of arterial hypertension. The aim of this work was to study and compare the molecular mechanisms of the antioxidant properties of l-carnitine and captopril in spontaneously hypertensive rats (SHR). Antioxidant enzyme activity/regulation (glutathione peroxidase, glutathione reductase and superoxide dismutase) was measured in the erythrocytes and hearts of SHR. The molecular expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase, angiotensin converting enzyme (ACE), angiotensin II type I receptor (AT(1) receptor) and NF-kappaB/IkappaB system was also measured in the hearts of these animals. Both l-carnitine and captopril augmented the antioxidant defense capacity in SHRs. This effect was mediated by an upregulation of antioxidant enzymes, an increase in the plasma total antioxidant capacity and a reduction of lipid peroxidation and superoxide anion production in the heart. The administration of both compounds to hypertensive animals also produced an upregulation of eNOS and a normalization of ACE, angiotensin AT(1) receptor, and the NF-kappaB/IkappaB system expression. In addition, captopril reduced the arterial blood pressure and the relative heart weights back to control values, whereas l-carnitine caused only a partial reduction of blood pressure values and did not alter the cardiac hypertrophy found in SHRs. In conclusion, we have found that l-carnitine and captopril have a similar antioxidant effect in the hearts of hypertensive rats. The molecular regulation of antioxidant enzymes through an inhibition of the renin-angiotensin system and a modulation of the NF-kappaB/IkappaB system seems to be responsible for this antioxidant effect.
Miguel-Carrasco
José L
JL
Departamento de Fisiología y Zoología, Universidad de Sevilla, Spain.
Monserrat
María T
MT
Mate
Alfonso
A
Vázquez
Carmen M
CM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000378:metabolism*
D002216:Captopril; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D002331:Carnitine