BACKGROUND: We have known that endothelial nitric-oxide synthase (eNOS) and oxidative stress may play a key role in cardiac performance in failing rat hearts. However, the interactions between eNOS or oxidative stress and bradykinin (BK) under treatment of calcium channel blockers (CCBs) remain unknown. To elucidate the mechanism underlying the cardioprotective effect of long-acting dihydropyridine CCBs, we evaluated the effect of benidipine on the BK-eNOS and NAD(P)H oxidase pathway in Dahl salt-sensitive (DS) rats with heart failure. METHODS: 11-week-old DS rats were treated with one of the following drug combinations for 7 weeks until the onset of the failing stage: vehicle, BK B2 receptor antagonist (FR172357 (FR)) alone, hydralazine, benidipine, and benidipine plus FR. The left ventricular end-systolic pressure-volume relationship (ESPVR) (contractility: Ees) was evaluated using a conductance catheter. RESULTS: Downregulated Ees and per cent of fractional shortening (%FS) assessed by echocardiography and eNOS expression in the failing stage were both significantly increased by using benidipine; this result was not found, however, when using FR alone or hydralazine or benidipine plus FR. Upregulated expression of NAD(P)H oxidase p22phox and p47phox and lectin-like oxidized low-density lipoprotein receptor-1, and downregulated superoxide dismutase-1 (SOD-1) were significantly ameliorated by benidipine, but not by FR alone or by hydralazine or benidipine plus FR. Benidipine effectively inhibited vascular lesion formation and suppressed atrial natriuretic peptide (ANP) and transforming growth factor-beta1 (TGF-beta1), but this was not the case when using FR alone or hydralazine or benidipine plus FR. CONCLUSIONS: These results suggest that benidipine may be useful for cardioprotective agents in preventing the cardiac dysfunction and remodeling associated with the BK-eNOS and oxidative stress pathway.
BACKGROUND: We have known that endothelial nitric-oxide synthase (eNOS) and oxidative stress may play a key role in cardiac performance in failing rat hearts. However, the interactions between eNOS or oxidative stress and bradykinin (BK) under treatment of calcium channel blockers (CCBs) remain unknown. To elucidate the mechanism underlying the cardioprotective effect of long-acting dihydropyridine CCBs, we evaluated the effect of benidipine on the BK-eNOS and NAD(P)H oxidase pathway in Dahl salt-sensitive (DS) rats with heart failure. METHODS: 11-week-old DS rats were treated with one of the following drug combinations for 7 weeks until the onset of the failing stage: vehicle, BK B2 receptor antagonist (FR172357 (FR)) alone, hydralazine, benidipine, and benidipine plus FR. The left ventricular end-systolic pressure-volume relationship (ESPVR) (contractility: Ees) was evaluated using a conductance catheter. RESULTS: Downregulated Ees and per cent of fractional shortening (%FS) assessed by echocardiography and eNOS expression in the failing stage were both significantly increased by using benidipine; this result was not found, however, when using FR alone or hydralazine or benidipine plus FR. Upregulated expression of NAD(P)H oxidase p22phox and p47phox and lectin-like oxidized low-density lipoprotein receptor-1, and downregulated superoxide dismutase-1 (SOD-1) were significantly ameliorated by benidipine, but not by FR alone or by hydralazine or benidipine plus FR. Benidipine effectively inhibited vascular lesion formation and suppressed atrial natriuretic peptide (ANP) and transforming growth factor-beta1 (TGF-beta1), but this was not the case when using FR alone or hydralazine or benidipine plus FR. CONCLUSIONS: These results suggest that benidipine may be useful for cardioprotective agents in preventing the cardiac dysfunction and remodeling associated with the BK-eNOS and oxidative stress pathway.
Authors: E M Seymour; Andrew A M Singer; Maurice R Bennink; Rushi V Parikh; Ara Kirakosyan; Peter B Kaufman; Steven F Bolling Journal: J Gerontol A Biol Sci Med Sci Date: 2008-10 Impact factor: 6.053
Authors: José Luis Miguel-Carrasco; Ana Baltanás; Carolina Cebrián; María U Moreno; Begoña López; Nerea Hermida; Arantxa González; Javier Dotor; Francisco Borrás-Cuesta; Javier Díez; Ana Fortuño; Guillermo Zalba Journal: Oxid Med Cell Longev Date: 2012-06-03 Impact factor: 6.543
Authors: Muhammad Shahzad Chohan; Mahesh Attimarad; Katharigatta Narayanaswamy Venugopala; Anroop Balachandran Nair; Nagaraja Sreeharsha; Efren Ii Plaza Molina; Ramling Bhagavantrao Kotnal; Sheeba Shafi; Marysheela David; Pottathil Shinu; Abdulrahman Ibrahim Altaysan; Abdulmalek Ahmed Balgoname Journal: Int J Environ Res Public Health Date: 2022-06-14 Impact factor: 4.614