Cardiovascular effects of verapamil in patients with essential hypertension.

Schmieder, R. E.; Messerli, Franz H.; Garavaglia, Guillermo E.; Núñez, Boris D.

doi:10.1161/01.cir.75.5.1030

Cited by 113 publications

(21 citation statements)

References 58 publications

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“…Ver has been shown to have minimal effect on HR when delivered via intracoronary injection. However, intravenous infusion of Ver results in a reflex increase in HR (43). To maintain cardiac output, HR would increase.…”

Section: Discussionmentioning

confidence: 99%

Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle

Schroder

Magyar

Burgess

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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(41), although in late-stage heart failure the consensus finding is that I Ca,L declines (47). The unchanged level of I Ca,L in all but late-stage heart failure suggests that ventricular myocytes may have the capacity to homeostatically regulate I Ca,L .At the plasma membrane the Ca 2ϩ channel complex exists as a heteromultimer consisting of the ␣ 1 -subunit (Ca V 1.2), a cytosolic ␤-subunit (Ca V ␤ 2 ), and a covalently linked ␣ 2 ␦-subunit. Ca V 1.2, the pore-forming subunit, determines ion selectivity and voltage sensitivity and is a binding site for clinically used Ca 2ϩ channel blockers. Ca V ␤ coexpression primarily increases Ca V 1.2 current density in heterologous expression systems (4,8,21,48) and in myocytes that overexpress Ca V ␤ (45). In addition to increasing functional expression, Ca V ␤s alter channel kinetics (29,36,44) and voltage dependence (5, 28, 39). Among the accessory subunits, the Ca V ␤s are the only accessory proteins known to increase current density. In contrast to Ca V ␤, the ␣ 2 ␦-subunit has modest effects on channel current density and has variable effects on channel voltage dependence and kinetics (6,25,26,31). Overall, Ca V ␤ 2 in the heart serves as a positive regulator of I Ca,L (11). We recently showed (13,19) channel function. Thus both positive and negative regulators, in the form of auxiliary proteins, influence ultimate I Ca,L density. Ca 2ϩ channel blockers (CCBs) are frequently used to regulate blood pressure in hypertensive patients (22,32,38); however, little is known about the long-term cardiac effects of these drugs on cardiac myocytes. The primary objective of this study was to test the hypothesis that cardiac I Ca,L is homeostatically regulated. We postulated that Ca 2ϩ entering through the L-type channel provides feedback regulation. According to our hypothesis, decreasing I Ca,L , such as via chronic CCB, would elicit upregulation of I Ca,L . Conversely, stressors that acutely increase cytosolic Ca 2ϩ cause long-term decreases of I Ca,L as in heart failure (7, 46). Our results demonstrate that long-term Ca 2ϩ channel blockade induces an increase of Ca V 1.2 mRNA and protein and significantly increases basal I Ca,L . In contrast, chronic ␤-adrenergic stimulation induces upregulation of positive and negative regulators of I Ca,L with no significant change in basal I Ca,L . Together, these results suggest that the main pore-forming subunit plays a greater role in determining I Ca,L than auxiliary subunits. MATERIALS AND METHODSMini-osmotic pumps. Female or male ICR mice (12-14 wk of age) weighing between 25 and 30 g were anesthetized with a ketaminexylazine mixture (ip), allowing the subcutaneous implantation of mini-osmotic pumps (Alzet, model 2001). The pumps were filled with verapamil (Ver), isoproterenol (Iso), isoproterenol and verapamil (Iso ϩ Ver), or vehicle alone (0.02% ascorbic acid). Mice carrying drug-loaded minipumps are abbreviated as Iso, Ver, and Iso ϩ Ver for pumps containing isoproterenol, verapamil, or the two drugs together. Control animals c...

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Section: Discussionmentioning

confidence: 99%

Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle

Schroder

Magyar

Burgess

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Como a relação entre a ingestão de sódio e a hipertensão arterial é ainda controversa 20 , e pelo fato de não ter sido feita a avaliação do sódio total alimentar nos indivíduos do grupo de referência, não foram utilizados os dados da ingestão de sódio referentes ao grupo de hipertensos, no presente estudo. Entre as mulheres, o maior índice de massa corporal entre as hipertensas poderia ser um fator a confundir a influência da diferença de ingestão média de cál-cio entre os dois grupos, em relação ao aparecimento de hipertensão arterial 39 . A diferença entre as ingestões médias de cálcio se manteve, mesmo quando corrigidas pelo peso.…”

Section: Discussionunclassified

Avaliação da ingestão dietética de cálcio em indivíduos adultos portadores de hipertensão arterial idiopática

Waib

Papini-Berto²,

Habermann

et al. 1992

Rev. Saúde Pública

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WAIB, P.H. et al. Avaliação da ingestão dietética de cálcio em indivíduos adultos portadores de hipertensão arterial idiopática. Rev. Saúde públ., S. Paulo, 26 (1): 27 -33, 1992. Foi estudada a relação entre a ingestão dietética de cálcio e os demais parâmetros alimentares e antropométricos em 60 indivíduos adultos, portadores de hipertensão arterial idiopática (10 homens e 50 mulheres), com média etária de 48,6 anos, seguidos no Centro de Hipertensão Arterial do Hospital das Clínicas da Faculdade de Medicina de Botucatu (SP), Brasil. Foram utilizados três métodos diferentes de inquérito aumentar em três diferentes ocasiões: recordatório de 24h, questionário de freqüência alimentar, dirigido para ingestão de cálcio, e registro alimentar de 3 dias. As médias de ingestão de cálcio, extraídas desses inquéritos, foram semelhantes, mostrando que, em relação á ingestão de cálcio, esses métodos de inquérito alimentar podem ser utilizados indistintamente com o objetivo de se mensurar à ingestão de cálcio de um grupo de indivíduos. Além da ingestão de cálcio, foi avaliada a ingestão protéico-calórica e de diversos outros nutrientes, assim como realizada a antropometria desse grupo de hipertensos em três ocasiões diferentes, com intervalos variando de duas semanas a 15 meses. Quando comparado a um grupo de referência local, constituído de indivíduos sadios, com média etária semelhante, o grupo de hipertensos mostrou ter menor ingestão média de cálcio. Comparados por sexo, os homens dos dois grupos exibiram perfis nutricional e antropométrico semelhantes. Em relação às mulheres, houve diferenças quanto à ingestão protéico-calórica, o que se supõe ser devido à ingestão menor do leite e derivados entre as hipertensas. Estas estavam mais pesadas que as mulheres do grupo de referências, à custa de maior massa muscular, provavelmente devido a maior atividade física. Concluiu-se que o cálcio dietético foi o principal item alimentar que distinguiu hipertensos de normotensos. Como existem estudos clínicos comprovando o efeito benéfico da suplementação de cálcio na redução dos níveis pressóricos de indivíduos hipertensos, sugere-se a repetição deste tipo de trabalho, em outros locais, visando ao embasamento de programa nacional de suplementação de cálcio dietético entre indivíduos hipertensos idiopáticos. IntroduçãoTem sido crescente o interesse por medidas terapêuticas não farmacológicas que possam auxiliar no controle da hipertensão arterial. Entre elas pode-se destacar a prática do exercício moderado e habitual, perda de peso em indivíduos obesos, limitação da ingestão alcoólica, restrição do consumo de sal e gorduras saturadas e suplementação da ingestão de potássio e cálcio, se houver deficiências 20,25 . A participação do cálcio intracelular na regulação do tônus vascular tem sido fundamentada em vários mecanismos bioquímicos 29,46 . Além disso, o efeito hipotensor da suplementação de cálcio em uma parcela de indivíduos hipertensos idiopáticos parece ser tanto maior quanto menor for a ingestão basal de cálcio entre estes ind...

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“…45 Verapamil has also been shown to be superior to a beta-blocker in reduction of LVH without depressing LV function in elderly subjects. 46 In a recently published study, Arrighi et al 47 showed that verapamil enhances LV diastolic filling in normotensive middle-aged and elderly subjects without affecting systolic function.…”

Section: Therapeutic Assumptionsmentioning

confidence: 99%

The heart in the hypertensive elderly

Grodzicki

Messerli

1998

J Hum Hypertens

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Left ventricular (LV) mass progressively increases throughout life, reaching its greatest magnitude in senescence. In the normotensive elderly, left ventricular hypertrophy (LVH) is mostly a consequence of a degenerative process in connective tissue. In hypertensive patients, LVH results from an increase in muscle mass and fibrotic tissue. LVH by echocardiographic criteria can be found in up to 50% of elderly patients with hypertension.Although associated with aging, LVH is associated with a higher rate of non-fatal and fatal cardiovascular events. Even in the absence of coronary stenosis, LVH is associated with reduced coronary reserve, increased number of arrhythmias and progressive deterioration in Keywords: essential hypertension; elderly; left ventricular hypertrophy; drug therapy Left ventricular hypertrophyUnlike other organs, the heart does not atrophy with age; in fact even in normotensive subjects left ventricular (LV) mass progressively increases throughout life. Various studies have documented an increase in wall thickness with age in the presence of unchanged chamber volume. [1][2][3] In addition to the increased size of the myocytes, the aging heart is characterised by a high rate of degenerative age-associated findings such as lipid deposition, tubular dilatation and decreased mitochondrial oxidative phosphorylation.3,4 Concomitantly, the amount of elastic tissue, collagen and fat increases. Therefore, even in normotensive subjects LV mass progressively increases throughout life, reaching its greatest magnitude in senescence. The prevalence of electrocardiographically diagnosed LV hypertrophy (ECG-LVH) in the population-based studies has been described as 4.2% to 16.9% according to the Minnesota criteria. 5 The Cardiovascular Health Study, 6 in which electrocardiograms of 5150 adults older than 65 years were analysed, showed that according to the Minnesota code, LVH was found in 4.1% of women and 4.3% of men. In the Framingham study the prevalence of ECG-LVH rose linearly with age. and/or density of vasoconstrive receptors (alpha) to vasorelaxing receptors (beta) lead to the decrease in compliance of large arteries and higher peripheral resistance.3 Other factors possibly contributing to increased BP in the elderly population are decreased oestrogen production in women, increased level of catecholamines, obesity, high prevalence of renal insufficiency and frequent consumption of nonsteroidal anti-inflammatory agents. The prevalence of hypertension in the elderly may reach 60% of the general population. 8 LVH and hypertensionLVH by echocardiographic criteria can be found in up to 50% of elderly patients with hypertension. 9The hypertrophic senescent heart in the morphometric study of Olivetti et al 10 was characterised by an increase in average myocyte cell volume per nucleus and an augmentation in the total number of myocyte nuclei in the ventricle myocardium. These processes were associated with 95% enlargement of the myocardial interstitium. In hypertensive patients irrespective of age, LVH is a...

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Cardiovascular effects of verapamil in patients with essential hypertension.

Cited by 113 publications

References 58 publications

Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle

Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle

Avaliação da ingestão dietética de cálcio em indivíduos adultos portadores de hipertensão arterial idiopática

The heart in the hypertensive elderly

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Cardiovascular effects of verapamil in patients with essential hypertension.

Cited by 113 publications

References 58 publications

Chronic verapamil treatment remodelsICa,Lin mouse ventricle

Chronic verapamil treatment remodelsICa,Lin mouse ventricle

Avaliação da ingestão dietética de cálcio em indivíduos adultos portadores de hipertensão arterial idiopática

The heart in the hypertensive elderly

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Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle

Chronic verapamil treatment remodelsI_Ca,Lin mouse ventricle