Inhibitory Effects of Carvedilol on Calcium Channels in Vascular Smooth Muscle Cells.

Nakajima, Toshiaki; Ma, Ji; Iida, Hidehiro; Iwasawa, Kuniaki; Jo, Taisuke; Omata, Masao; Nagai, Ryozo

doi:10.1536/jhj.44.963

Cited by 19 publications

(10 citation statements)

References 37 publications

(38 reference statements)

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“…19) In our study, we observed a reduction in blood pressure in both patient groups with carvedilol 6.25 mg and 25 mg, but not in the 12.5 mg group. This may be due to different etiologies and left ventricular reserves.…”

Section: Discussionsupporting

confidence: 43%

Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Tsay

Chu

et al. 2004

Jpn Heart J

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SUMMARYCarverdilol has a variable outcome in treating patients with chronic heart failure. This prospective single-center study evaluated the predictors of clinical variables in determining favorable outcomes in treating chronic heart failure patients with carvedilol. The relation between clinical variables and maintenance doses of carvedilol was also determined.Seventy chronic heart failure patients (mean age, 62.2 years, 50 males and 20 females) with a left ventricular ejection fraction < 35% and functional class II-III were enrolled in the study. The patients were clinically followed-up for at least 24 months. Patients were considered to have a favorable outcome if they had no decreases in functional class or quality-of-life score, an increase in left ventricular ejection fraction > 5%, were not admitted to hospital due to worsening heart failure, and free of cardiac mortality.Patients with favorable outcomes had a younger age (P = 0.021), higher baseline systolic blood pressure (P = 0.080), better baseline functional class (P = 0.001), and a higher tolerated dose of carvedilol (P = 0.026) than those in the unfavorable group.In this primarily Chinese cohort of chronic heart failure patients, those with favorable outcomes were likely to be young, have a high baseline systolic blood pressure, and good baseline functional class. (Jpn Heart J 2004; 45: 823-832)

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Section: Discussionsupporting

confidence: 43%

Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Tsay

Chu

et al. 2004

Jpn Heart J

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“…In the same way, a reduction of Ca 2+ -ATP pump activity affects electrolyte removal from cytosol, reducing parietal elasticity. 27,28 Carvedilol seems to restore Ca 2+ homeostasis and remove actomyosin complex, improving active relaxation. These ancillary actions could explain the observed diastolic restoration and changes in LV filling pattern.…”

Section: Discussionmentioning

confidence: 99%

Left Ventricular Diastolic Function Improvement by Carvedilol Therapy in Advanced Heart Failure

Palazzuoli

Quatrini

Vecchiato

et al. 2005

Journal of Cardiovascular Pharmacology

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Carvedilol treatment in chronic heart failure (CHF) patients has been demonstrated to reduce mortality by improving cardiac systolic function and reducing left ventricular adverse remodeling. However, the effects of the drug on left ventricular (LV) filling are less studied. In this study we evaluated early and long-term diastolic cardiac modifications by an echo-Doppler method during carvedilol therapy in patients with advanced CHF and pseudonormal or restrictive filling pattern. We studied 58 patients with severe but stable CHF (39 in class NYHA III and 19 in IV) having systolic and diastolic dysfunction caused by idiopathic or ischemic cardiomyopathy. Thirty-two patients were randomized to receive previous treatment plus carvedilol (group 1) and 26 continued standard therapy (group 2). In all subjects we evaluated LV volumes, LV mass, LV ejection fraction (EF), and the following transmitral filling parameters: early wave (E), atrial wave (A), E/A ratio, deceleration time (DT), and isovolumetric releasing time (IVRT). After 4 months of therapy, the carvedilol group showed a significant increase of A wave (P < 0.001), DT (P < 0.0001), IVRT (P < 0.0001), and a significant reduction of E/A ratio (P < 0.0005) with respect to group 2. Further improvement was observed at 12 months (A P < 0.0005; DT P < 0.00002; IVRT P < 0.000004; E/A P < 0.0008), although an E wave reduction was observed in group 1 with respect to controls (P < 0.001). Moreover, after 1 year of follow-up a reduction of systolic volume (P < 0.001) and pulmonary pressure (P < 0.0001) and consequent increase of EF (P < 0.001) was observed in the carvedilol group. Carvedilol treatment improved diastolic function in CHF with severe diastolic and systolic impairment at early time, converting a restrictive or pseudonormal filling pattern into an altered pattern. These changes remained significant after 1 year of therapy together with improvement in systolic function.

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“…A decreased of intracellular Ca 2+ concentration will elicit relaxation. The previous study has suggested that Carvedilol exhibited the inhibitory effects on Ca 2+ mobilization and this unique action may contribute to its antihypertensive effect [3]. Using KEGG database and literature mining, we have linked the intracellular metabolic variations to the vascular smooth muscle relaxation pathway (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

“…Carvedilol, a nonselective β -antagonist ( β 1 , β 2 ), has proven potent antihypertensive activity and also effective in the treatment of coronary artery disease and congestive heart failure [2]. It also possesses calcium channel blocking effect by inhibiting voltage-dependent L-type Ca 2+ in vascular smooth muscle cells [3]. Carvedilol has an asymmetric carbon atom, which gives rise to S - and R -enantiomers.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of Cellular Responses to Carvedilol Enantiomers in Vascular Smooth Muscle Cells

et al. 2010

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Carvedilol is a non-selective β-blocker indicated in the treatment of hypertension and heart failure. Although the differential pharmacological effects of individual Carvedilol enantiomer is supported by preceding studies, the cellular response to each enantiomer is not well understood. Here we report the use of GC-MS metabolomic profiling to study the effects of Carvedilol enantiomers on vascular smooth muscle cells (A7r5) and to shed new light on molecular events underlying Carvedilol treatment. The metabolic analysis revealed alternations in the levels of 8 intracellular metabolites and 5 secreted metabolites in A7r5 cells incubated separately with S- and R-Carvedilol. Principal component analysis of the metabolite data demonstrated the characteristic metabolic signatures in S- and R-Carvedilol-treated cells. A panel of metabolites, including L-serine, L-threonine, 5-oxoproline, myristic acid, palmitic acid and inositol are closely correlated to the vascular smooth muscle contraction. Our findings reveal the differentiating metabolites for A7r5 cells incubated with individual enantiomer of Carvedilol, which opens new perspectives to employ metabolic profiling platform to study chiral drug-cell interactions and aid their incorporation into future improvement of β-blocker therapy.

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Inhibitory Effects of Carvedilol on Calcium Channels in Vascular Smooth Muscle Cells.

Cited by 19 publications

References 37 publications

Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Predictors of Stable Outcome in Treating Chronic Heart Failure Patients With Carvedilol

Left Ventricular Diastolic Function Improvement by Carvedilol Therapy in Advanced Heart Failure

Metabolomic Profiling of Cellular Responses to Carvedilol Enantiomers in Vascular Smooth Muscle Cells

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