Hereditary hypertriglyceridemic (hHTG) rats are characterized by increased blood pressure and impaired endotheliumdependent 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 4th 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., J. Török, I. L'upták, J. Matúšková, O. Pecháňová, J. Zicha, J. Kuneš, F. Šimko., and Obsahuje bibliografii
We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58±1.12 vs. 13.39±1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34±0.93 vs. 21.22±4.28 µmol/g d.w., p<0.05) and higher coronary flow recovery (by 25 %), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway., J. Divišová, H. Vavřínková, M. Tutterová, L. Kazdová, E. Meschišvili., and Obsahuje bibliografii
The effects of various doses of L-arginine, a nitric oxide substrate, on lithium-pilocarpine-induced seizures were studied in rats. Rats were implanted with chronic, stainless steel screw electrodes epidurally for electrocortical recordings. A control group received 3 mEq/kg LiCl (i.p.) and 24 h later 45 mg/kg pilocarpine HCl (i.p.). Two different experimental procedures were followed: (1) L-arginine was applied in doses of 100 mg/kg, 300 mg/kg or 500 mg/kg (i.p.), 30 min before pilocarpine injection; (2) 300 mg/kg, 500 mg/kg or 1000 mg/kg (i.p.) L-arginine was injected either 5 min or 30 min after the onset of status epilepticus (SE). L-arginine (300 mg/kg) injected 30 min before pilocarpine significantly reduced the percentage of SE, but did not change the latency to SE or 24-hour survival. These parameters were not significantly affected by the 100 mg/kg or 500 mg/kg dose of L-arginine. On the other hand, no dose of L-arginine that was applied after SE had begun, had any significant influence on the seizures. We concluded that L-arginine may prevent seizure activity in some but not all doses, and does not have any effect on the ongoing seizure activity., B. Noyan, G. Güleç., and Obsahuje bibliografii
NG-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 NOproduction 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-arginineregression (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., F. Šimko, A. Potáčová, V. Pelouch, L'. Paulis, J. Matúšková, K. Krajčírovičová, O. Pecháňová, M. Adamcová., and Obsahuje bibliografii
The increase of radical forms of mitochondrial respiratory chain compounds (MRCC) is an indicator of an increased risk of the formation of oxygen radicals. Using electron paramagnetic resonance (EPR), we found an increase of signals corresponding to ubisemichinone radical (·QH) and ironsulfur proteins radical forms (·FeS) of these respiratory chain compounds during ischemia in the isolated perfused rat heart (·QH increased from 1.51 to 3.08, ·FeS1 from 1.14 to 2.65 arbitrary units). During the 5-min reperfusion, the signals returned to normoxic levels. In isolated mitochondria exposed to anoxia and reoxygenation the radical forms of ·QH and ·FeS2 changed in a similar manner as in the intact heart. A combination of in vivo captopril treatment and in vitro L-arginine administration significantly decreased the levels of MRCC radicals in the isolated myocardium (·QH from 2.61 to 1.72 and ·FeS1 from 1.82 to 0.46 under normoxia; ·QH from 4.35 to 2.66 and ·FeS1 from 1.93 to 1.35 during ischemia). This decrease in MRCC radical forms was associated with increased NO levels in the perfusate, determined as NO2-/ NO3-, as well as tissue NO levels determined using EPR as the dinitrosyl iron complex (DNIC). These results provide new information about the cardioprotective effects of ACE inhibitors and L-arginine., H. Vavřínková, M. Tutterová, P. Stopka, J. Divišová, L. Kazdová, Z. Drahota., and Obsahuje bibliografii
L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine-induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5 mg/ml p.o.), L-arginine + apocynin (2.5 mmol/l p.o.), L-arginine + catalase (10000 U/kg/day i.p.) and L-arginine plus apocynin + catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs. 91±2 mmHg) and heart rate (298±21 vs. 254±15 bpm), enhanced urinary output (21.5±4.2 vs. 32±1.9 ml/24 h, increased creatinine clearance (1.72±0.56 vs. 2.62±0.40 ml/min/kg), and fractional sodium excretion (0.88±0.16 vs. 1.18±0.16 %), caused proteinuria (28.10±1.93 vs. 35.26±1.69 mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs. 258±5 bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13 m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by ~51 %, P<0.05) but decreased superoxide dismutase (by ~31 %, P<0.05) and total antioxidant capacity (by ~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine-treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in the states of oxidative stress.