TY - JOUR
T1 - Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats
AU - Vilskersts, Reinis
AU - Kuka, Janis
AU - Svalbe, Baiba
AU - Cirule, Helena
AU - Liepinsh, Edgars
AU - Grinberga, Solveiga
AU - Kalvinsh, Ivars
AU - Dambrova, Maija
N1 - Funding Information:
This study was supported by the European Social Foundation (ESF) agreement No. 2009/0147/1DP/1.1.2.1.2/09/IPIA/VIAA/009 and the Latvian State Research Program 2010.10-4/VPP-4.
PY - 2011
Y1 - 2011
N2 - Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses above (n = 10). During the experiment, control group animals continued to consume a diet with normal salt content. Administration of the combination significantly improved the survival rate for 50% of the population. None of the tested compounds or their combination influenced high salt intake-induced hypertension, while treatment with mildronate and the combination for 8 weeks significantly decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt diet had no influence on systolic function of the heart, but it induced thickening of the ventricular walls and development of heart hypertrophy that was not improved by the administration of tested compounds. In addition, administration of the combination attenuated the development of endothelial dysfunction in isolated aortic rings. In conclusion, our results demonstrate that treatment with a combination of L-carnitine and mildronate is protective against hypertension-induced complications in an experimental model of salt-induced hypertension.
AB - Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at the doses above (n = 10). During the experiment, control group animals continued to consume a diet with normal salt content. Administration of the combination significantly improved the survival rate for 50% of the population. None of the tested compounds or their combination influenced high salt intake-induced hypertension, while treatment with mildronate and the combination for 8 weeks significantly decreased resting heart rate by 12% and 10%, respectively. Feeding with high salt diet had no influence on systolic function of the heart, but it induced thickening of the ventricular walls and development of heart hypertrophy that was not improved by the administration of tested compounds. In addition, administration of the combination attenuated the development of endothelial dysfunction in isolated aortic rings. In conclusion, our results demonstrate that treatment with a combination of L-carnitine and mildronate is protective against hypertension-induced complications in an experimental model of salt-induced hypertension.
KW - Dahl salt-sensitive rats
KW - Endothelial dysfunction
KW - Hypertension
KW - L-carnitine
KW - Mildronate
UR - http://www.scopus.com/inward/record.url?scp=80051530000&partnerID=8YFLogxK
U2 - 10.1016/S1734-1140(11)70587-4
DO - 10.1016/S1734-1140(11)70587-4
M3 - Article
AN - SCOPUS:80051530000
SN - 1734-1140
VL - 63
SP - 752
EP - 762
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 3
ER -