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L-arginine fails to prevent heart remodeling but prevents a coenzyme Q decline in L-name-induced hypertension
CALCIUM FAILURE:
IN CHRONIC FRIEND OR
HEART ENEMY?
Fedor Slmko Department of Pathophyslology and 3’d Chmc of Mechcme. School of Medicine, Comenius IJmversity, Bratislava. Slovak Republic Chronic heart failure (CHF) IS associated with chsturbanccs of calcium metabohsm participating in contractility alterations. Positive inotropic drugs were considered the prmcipal therapeutic means. Later, the Increased neurohumoral activation was revealed to be linked lo worse prognosis. Thus, depression of excessive humoral activity seemed to be reasonable approach to treatment of CHF. Large climcal trials only in part confirmed the original presumptions. ACE-inhibitors, (j-blockers and AT1 receptor blockers were proved to reduce morblchty and mortality. Calcium antagonists does not seem 10 reduce mortahty. Addition of positive motroplc agents to ACE-inhibitors resulted m disappomhng results with mortality enhancement. The only exceptlon IS digoxm which improved morbidity without enhancing mortality m CHF patients. Conclusion: Improvement of calcium metabohsm m the myocardium IS not the principle therapeutic aim in CHF patients. The inhibition of neurohumoral activation seems to be the only reliable way of prognosrs Improvement. Acknowledgement: The I!7529120 is appreciated.
support
of VEGA
SIMVASTATIN FAILS TO PREVENT REMODELING OF THE LEFT VENTRICLE AORTA IN GNAME INDUCED HYPERTENSION
grant No
AND
Fedor Simko, Jana Matuskova, Ivan Luptak. ‘Olga Pcchanova, ‘Pavol Babal Dept. of Pathophyslology and 2Dept. of Pathology, School of Medicme, ‘Institute of Physiology. Slovak Academy of Sciences, Bratlslava, Slovak Republic The aim of the present study was to determine whether treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhlbltor, simvastatin, could prevent remodeling of the IeA ventricle and aorta in L-NAME-induced hypertension. Four groups of rats were investigated after six weeks of treatment: control, simvastatm, L-NAME and I.NAME+simvastatin. In the L-NAME group, NO-synthase (NOS) achvlty was decreased m the left ventricle (LV), kidney and brain. Thus was associated with the development of hypertension, left ventricular hypertrophy, fibrosis, increased DNA concentration in the LV and thlckenmg of the aorta. Simultaneous treatment with simvastatm prevented NOS activity reduction m the ludney and brain, and m part prevented hypertension development. Nevertheless, hypertrophy, tibrosls and increased DNA concentrahon of the LV and thickening of the aorta were unaffected by simultaneous slmvastatm treatment. Slmvastatin failed to prevent remodeling of the heart and aorta m L-NAME-induced hypertension The support of VEGA grant l/7529/20 IS apprectated.
L-ARGININE FAILS TO PREVENT REMODELING BUT PREVENTS DECLINE IN L-NAME-INDUCED
HEART A COENZYME HYPERTENSION
Q
Fedor Sunko, Jana Matuskova, Ivan Luptak, Iveta Bematova’, Olga Pechanova’, Zuzana Braunova’, Jatmlla Kucharska’. Anna Gvozdjakova2. Dept. of Pathophysiology and ‘Pharmacoblochemlcal Laboratory. Medical Faculty. ‘Institute of Physiology, Slovak Academy of Sciences. Bratislava, Slovak Republic We Investigated whether the substrate for nimc oxide (NO) synthesis L-arginine IS able to modify hypertension and left ventricular hypertrophy (LVH) development Induced by chronic blockade of NO-synthase actlvlty by L-NAME. Four groups of rats were Investigated: control, L-arginme, L?IAME and L-XAh4E + L-arginine. In the L-NAME group, NO synthase activity was decreased m the left ventricle (LV), kidney and brain and hypertension, left ventricular hypertrophy (I-VII) and fibrosis of the 1.V developed. The LVH was associated with a decrease of coenzyme CoQ9 and CoQlO concentrations in the LV. Simultaneous treatment with L-arginme prevented NOS activity dimmutlon m the 1.V but completely failed to prevent hypertension, LVH and fibrosis. Nevertheless. no dechne of CoQ9 and CoQlO concentrations m the LV was observed m the I.-argmme A L-NAME-group. Conclusion: L-argmme prevented the decline of CoQ9 and CoQlO levels m the LV in NOdeficIent hypertension but the remodeling of the 1.V was unaffected. The work was supported by the VEGA grant No. l/7529/20. REMODELING OF THE HEART IN THE HEREDITARY HYPERTRIGLYCERIDEMIC RAT: EFFECT OF CAPTOPRIL AND LNA.ME
Fedor Simko]. Ivan Luptak’, Jana Matuskova’, Pavol Babal’. Olga Pechanova’, Iveta Bematova’. Ivan Hulm’ ‘Department of Pathophysiology and ‘Department of Pathology, School of Mechcme, Comemus IJmverslty. Rratlslava and ‘Institute of Physiology, Slovak Academy of Sciences, Bratlslava, Slovak Republic We mvestlgated the remodeling process of the left ventricle (1.V) In hereditary hypertnglyceridemic (hHTg) hypertensive rats and its modlficatlon by captoprll (CAP) and L-NAME. Five groups of rats were Investigated: control Wistar /C/rats, hHTg rats, hHTg+CAP, hHTg&L-NAME and hHTg+CAP+L-NAME. In the hHTg group, the Increased systohc blood pressure (SBP) was hnked to hypertrophy of the 1.V with only rtummal fibrosis. Captoprll normahzed SBP and decreased the LVWlBW ratio. Chrome admmistration of L-NAME to the hHTg rats additlonally enhanced the already elevated SBP and stimulated fibrosis development m the LV compared to hHTg group, yet without an additlonal weight increase of the I.V. The combined Matment of the hHTg rats with CAP and LNAME resulted m normal SBP and a substantial reduction In the development of left ventricular hypemophy and fibrosis. Conclusion: The remodeling of the LV m hHTg rats IS not associated with fibrosis and does not seem to be determined by the renm-angiotensin-aldosterone system. Supported by the VEGA grant No. I/7529/20.
IN CHRONIC FRIEND OR
HEART ENEMY?
Fedor Slmko Department of Pathophyslology and 3’d Chmc of Mechcme. School of Medicine, Comenius IJmversity, Bratislava. Slovak Republic Chronic heart failure (CHF) IS associated with chsturbanccs of calcium metabohsm participating in contractility alterations. Positive inotropic drugs were considered the prmcipal therapeutic means. Later, the Increased neurohumoral activation was revealed to be linked lo worse prognosis. Thus, depression of excessive humoral activity seemed to be reasonable approach to treatment of CHF. Large climcal trials only in part confirmed the original presumptions. ACE-inhibitors, (j-blockers and AT1 receptor blockers were proved to reduce morblchty and mortality. Calcium antagonists does not seem 10 reduce mortahty. Addition of positive motroplc agents to ACE-inhibitors resulted m disappomhng results with mortality enhancement. The only exceptlon IS digoxm which improved morbidity without enhancing mortality m CHF patients. Conclusion: Improvement of calcium metabohsm m the myocardium IS not the principle therapeutic aim in CHF patients. The inhibition of neurohumoral activation seems to be the only reliable way of prognosrs Improvement. Acknowledgement: The I!7529120 is appreciated.
support
of VEGA
SIMVASTATIN FAILS TO PREVENT REMODELING OF THE LEFT VENTRICLE AORTA IN GNAME INDUCED HYPERTENSION
grant No
AND
Fedor Simko, Jana Matuskova, Ivan Luptak. ‘Olga Pcchanova, ‘Pavol Babal Dept. of Pathophyslology and 2Dept. of Pathology, School of Medicme, ‘Institute of Physiology. Slovak Academy of Sciences, Bratlslava, Slovak Republic The aim of the present study was to determine whether treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhlbltor, simvastatin, could prevent remodeling of the IeA ventricle and aorta in L-NAME-induced hypertension. Four groups of rats were investigated after six weeks of treatment: control, simvastatm, L-NAME and I.NAME+simvastatin. In the L-NAME group, NO-synthase (NOS) achvlty was decreased m the left ventricle (LV), kidney and brain. Thus was associated with the development of hypertension, left ventricular hypertrophy, fibrosis, increased DNA concentration in the LV and thlckenmg of the aorta. Simultaneous treatment with simvastatm prevented NOS activity reduction m the ludney and brain, and m part prevented hypertension development. Nevertheless, hypertrophy, tibrosls and increased DNA concentrahon of the LV and thickening of the aorta were unaffected by simultaneous slmvastatm treatment. Slmvastatin failed to prevent remodeling of the heart and aorta m L-NAME-induced hypertension The support of VEGA grant l/7529/20 IS apprectated.
L-ARGININE FAILS TO PREVENT REMODELING BUT PREVENTS DECLINE IN L-NAME-INDUCED
HEART A COENZYME HYPERTENSION
Q
Fedor Sunko, Jana Matuskova, Ivan Luptak, Iveta Bematova’, Olga Pechanova’, Zuzana Braunova’, Jatmlla Kucharska’. Anna Gvozdjakova2. Dept. of Pathophysiology and ‘Pharmacoblochemlcal Laboratory. Medical Faculty. ‘Institute of Physiology, Slovak Academy of Sciences. Bratislava, Slovak Republic We Investigated whether the substrate for nimc oxide (NO) synthesis L-arginine IS able to modify hypertension and left ventricular hypertrophy (LVH) development Induced by chronic blockade of NO-synthase actlvlty by L-NAME. Four groups of rats were Investigated: control, L-arginme, L?IAME and L-XAh4E + L-arginine. In the L-NAME group, NO synthase activity was decreased m the left ventricle (LV), kidney and brain and hypertension, left ventricular hypertrophy (I-VII) and fibrosis of the 1.V developed. The LVH was associated with a decrease of coenzyme CoQ9 and CoQlO concentrations in the LV. Simultaneous treatment with L-arginme prevented NOS activity dimmutlon m the 1.V but completely failed to prevent hypertension, LVH and fibrosis. Nevertheless. no dechne of CoQ9 and CoQlO concentrations m the LV was observed m the I.-argmme A L-NAME-group. Conclusion: L-argmme prevented the decline of CoQ9 and CoQlO levels m the LV in NOdeficIent hypertension but the remodeling of the 1.V was unaffected. The work was supported by the VEGA grant No. l/7529/20. REMODELING OF THE HEART IN THE HEREDITARY HYPERTRIGLYCERIDEMIC RAT: EFFECT OF CAPTOPRIL AND LNA.ME
Fedor Simko]. Ivan Luptak’, Jana Matuskova’, Pavol Babal’. Olga Pechanova’, Iveta Bematova’. Ivan Hulm’ ‘Department of Pathophysiology and ‘Department of Pathology, School of Mechcme, Comemus IJmverslty. Rratlslava and ‘Institute of Physiology, Slovak Academy of Sciences, Bratlslava, Slovak Republic We mvestlgated the remodeling process of the left ventricle (1.V) In hereditary hypertnglyceridemic (hHTg) hypertensive rats and its modlficatlon by captoprll (CAP) and L-NAME. Five groups of rats were Investigated: control Wistar /C/rats, hHTg rats, hHTg+CAP, hHTg&L-NAME and hHTg+CAP+L-NAME. In the hHTg group, the Increased systohc blood pressure (SBP) was hnked to hypertrophy of the 1.V with only rtummal fibrosis. Captoprll normahzed SBP and decreased the LVWlBW ratio. Chrome admmistration of L-NAME to the hHTg rats additlonally enhanced the already elevated SBP and stimulated fibrosis development m the LV compared to hHTg group, yet without an additlonal weight increase of the I.V. The combined Matment of the hHTg rats with CAP and LNAME resulted m normal SBP and a substantial reduction In the development of left ventricular hypemophy and fibrosis. Conclusion: The remodeling of the LV m hHTg rats IS not associated with fibrosis and does not seem to be determined by the renm-angiotensin-aldosterone system. Supported by the VEGA grant No. I/7529/20.