The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension.
BACKGROUND
The mechanism(s) underlying the effects of L-carnitine (beta-hydroxy-gamma-N-trimethylammonium-butyrate; LC) in cardiovascular diseases are not well clarified. Previous studies have demonstrated that oxidative stress and inflammation contribute to arterial hypertension, and antioxidant and/or anti-inflammatory therapies have been proposed. We hypothesized that LC might attenuate the hypertensive status through an inhibition of inflammation process.


METHODS
Heart mRNA expression and plasma levels of inflammatory markers, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were measured in rats that were made hypertensive with N(omega)-nitro-L-arginine methyl ester (L-NAME) and subjected to a simultaneous administration of LC. To clarify the role of the renin-angiotensin system (RAS) in this effect of LC, the activity and expression of angiotensin I-converting enzyme (ACE) as well as the expression of angiotensin II type I receptor (AT1R) in the heart were also determined.


RESULTS
LC produced a significant, but not complete, reduction of blood pressure in L-NAME-treated rats. Plasma levels and heart expression of IL-1 beta, IL-6, and TNF-alpha showed an increase in the L-NAME group, which was reversed by LC treatment. The plasma ACE activity was not modified between normotensive and hypertensive rats although LC treatment produced a reduction of these values in the latter. Finally, protein and mRNA expression of ACE and AT1R was enhanced in the heart of L-NAME-treated animals, and LC reversed these values.


CONCLUSIONS
The chronic administration of LC reduces blood pressure and attenuates the inflammatory process associated with arterial hypertension. LC might produce a partial inactivation in the RAS resulting in a reduction in the production and effects of angiotensin II.
Miguel-Carrasco
Jose L
JL
Department of Physiology and Zoology, Faculty of Pharmacy, University of Seville, Seville, Spain.
Mate
Alfonso
A
Monserrat
Maria T
MT
Arias
Jose L
JL
Aramburu
Oscar
O
Vázquez
Carmen M
CM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D002316:Cardiotonic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D007703:Peptidyl-Dipeptidase A; D002331:Carnitine; D019331:NG-Nitroarginine Methyl Ester