Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAME-induced hypertension.
- MeSH
- antagonisté mineralokortikoidních receptorů farmakologie terapeutické užití MeSH
- antihypertenziva farmakologie terapeutické užití MeSH
- aorta účinky léků patologie patofyziologie MeSH
- časové faktory MeSH
- hypertenze chemicky indukované komplikace farmakoterapie metabolismus patologie patofyziologie MeSH
- hypertrofie levé komory srdeční farmakoterapie etiologie metabolismus patologie patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků enzymologie MeSH
- NG-nitroargininmethylester MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- proliferace buněk účinky léků MeSH
- remodelace komor účinky léků MeSH
- replikace DNA účinky léků MeSH
- spironolakton farmakologie terapeutické užití MeSH
- srdeční komory účinky léků enzymologie MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endothelium-dependent relaxation of conduit arteries. The aim of this study was to investigate the effect of long-term (4 weeks) treatment of hHTG rats with three drugs which, according to their mechanism of action, may be able to modify the endothelial function: simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase), spironolactone (an antagonist of aldosterone receptors) and L-arginine (a precursor of nitric oxide formation). At the end of fourth week the systolic blood pressure in the control hHTG group was 148+/-2 mm Hg and in control normotensive Wistar group 117+/-3 mm Hg. L-arginine failed to reduce blood pressure, but simvastatin (118+/-1 mm Hg) and spironolactone (124+/-4 mm Hg) treatment significantly decreased the systolic blood pressure. In isolated phenylephrine-precontracted aortic rings from hHTG rats endothelium-dependent relaxation was diminished as compared to control Wistar rats. Of the three drugs used, only simvastatin improved acetylcholine-induced relaxation of the aorta. We conclude that both simvastatin and spironolactone reduced blood pressure but only simvastatin significantly improved endothelial dysfunction of aorta. Prominent increase in the expression of eNOS in large conduit arteries may be the pathophysiological mechanism underlying the protective effect of simvastatin in hHTG rats.
- MeSH
- acetylcholin farmakologie MeSH
- antagonisté mineralokortikoidních receptorů farmakologie terapeutické užití MeSH
- aorta účinky léků patofyziologie MeSH
- arginin farmakologie terapeutické užití MeSH
- časové faktory MeSH
- cévní endotel účinky léků enzymologie patofyziologie MeSH
- hypertriglyceridemie farmakoterapie genetika patofyziologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- noradrenalin farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- simvastatin farmakologie terapeutické užití MeSH
- spironolakton farmakologie terapeutické užití MeSH
- statiny farmakologie terapeutické užití MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- synthasa oxidu dusnatého, typ III MeSH
- vazodilatace účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vazokonstrikce účinky léků MeSH
- vazokonstriktory farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.
- MeSH
- antagonisté mineralokortikoidních receptorů farmakologie terapeutické užití MeSH
- arginin farmakologie terapeutické užití MeSH
- hypertenze chemicky indukované komplikace farmakoterapie metabolismus patofyziologie MeSH
- hypertrofie levé komory srdeční farmakoterapie etiologie metabolismus patofyziologie MeSH
- kolagen metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- myokard metabolismus patologie MeSH
- NG-nitroargininmethylester MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- remodelace komor účinky léků MeSH
- spironolakton farmakologie terapeutické užití MeSH
- spontánní remise MeSH
- svalové proteiny metabolismus MeSH
- velikost orgánu účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH