Effect of simvastatin on remodeling of the left ventricle and aorta in L-NAME-induced hypertension.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to prevent or reverse hypertrophy of the LV in several models of left ventricular hypertrophy. The aim of the present study was to determine whether treatment with simvastatin can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) remodeling in NG-nitro-L-arginine methyl ester(L-NAME)-induced hypertension. Four groups of rats were investigated: control, simvastatin (10 mg/kg), L-NAME (40 mg/kg) and L-NAME + simvastatin (in corresponding doses). Animals were sacrificed and studied after 6 weeks of treatment. The decrease of NO-synthase activity in the LV, kidney and brain was associated with hypertension, LV hypertrophy and fibrosis development and remodeling of the aorta in the L-NAME group. Simvastatin attenuated the inhibition of NO-synthase activity in kidney and brain, partly prevented hypertension development and reduced the concentration of coenzyme Q in the LV. Nevertheless, myocardial hypertrophy, fibrosis and enhancement of DNA concentration in the LV, and remodeling of the aorta were not prevented by simultaneous simvastatin treatment in the L-NAME treated animals. We conclude that the HMG-CoA reductase inhibitor simvastatin improved nitric oxide production and partially prevented hypertension development, without preventing remodeling of the left ventricle and aorta in NO-deficient hypertension.
Simko
Fedor
F
Department of Pathophysiology, School of Medicine, Comenius University, Sasinkova 4, 813 72, Bratislava, Slovak Republic. fedor.simko@fmed.uniba.sk
Matuskova
Jana
J
Luptak
Ivan
I
Krajcirovicova
Kristina
K
Kucharska
Jarmila
J
Gvozdjakova
Anna
A
Babal
Pavel
P
Pechanova
Olga
O
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003067:Coenzymes; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors; D005355:Fibrosis / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D003067:Coenzymes; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; D004247:DNA; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C024989:coenzyme Q10; C030571:ubiquinone 9; D019331:NG-Nitroarginine Methyl Ester