Fosinopril and amlodipine in the treatment of isolated systolic hypertension

Pavlović, Katica; Benc, D; Kmezić-Grujin, Jasna; Stojiljkovic, J.; Čemerlić-Ađić, Nadica; Miljković, Tatjana; Mesaros, Piroska

doi:10.2298/mpns0402045p

Cited by 4 publications

(3 citation statements)

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“…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.…”

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confidence: 99%

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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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confidence: 99%

“…Overall, Ca V ␤ 2 in the heart serves as a positive regulator of I Ca,L (11). We recently showed (13,19) (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.…”

mentioning

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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“…To our knowledge, this is the first clinical report comparing the efficacy of fosinopril and amlodipine in the treatment of children with primary hypertension. PavlovićK et al found no difference in BP control rates between fosinopril or amlodipine monotherapy for 3 months in patients older than 60 years with isolated systolic hypertension (76.6% vs. 79.9%) ( 27 ). Similar to their results, we found no difference in BP control rates between the two groups, but a 10% difference in the degree of SBP and DBP reductions, although this difference was no longer significant after adjustment.…”

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confidence: 99%

Efficacy of fosinopril and amlodipine in pediatric primary hypertension: a single-center observational study

Wang,

Shi,

Lin

et al. 2023

Front. Pediatr.

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ObjectiveFosinopril and amlodipine are commonly prescribed as first-line pharmacotherapeutic agents for pediatric hypertension, but there is a lack of comparative studies regarding the efficacy of these two drugs. We aimed to evaluate and compare the efficacy of fosinopril and amlodipine monotherapy in pediatric primary hypertension.MethodsThis was a single-center, bidirectional observational study. A total of 175 children and adolescents with primary hypertension receiving antihypertensive monotherapy from July 2020 to February 2023 were enrolled. According to antihypertensive drugs, they were divided into the fosinopril group (n = 96) and the amlodipine group (n = 79). Subgroup analysis was performed to compare the efficacy of the two groups in terms of blood pressure (BP) control rates and reductions following a 4-week treatment.ResultsAfter 4 weeks of treatment, both groups achieved significant reductions in systolic BP (SBP) and diastolic BP (DBP) by more than 18 mmHg and 6 mmHg, respectively, with BP control rates of 61.5% in the fosinopril group and 59.5% in the amlodipine group, revealing no significant differences in the antihypertensive efficacy between the two groups except for DBP control rate (FDR adjusted P > 0.05). Further subsequent subgroup analyses revealed that the reductions in SBP and DBP in the fosinopril group were significantly greater than those in the amlodipine group in patients of females and hypo-HDL-cholesterolemia (FDR adjusted P < 0.05), and there was a trend of difference, although not significant, in patients with central obesity and insulin resistance (IR) (FDR adjusted 0.05 < P ≤ 0.1). However, there were no significant differences in treatment efficacy in patients without these characteristics. Furthermore, hypertriglyceridemia did not exhibit a significant association with the difference in treatment efficacy between the two medications (FDR adjusted P > 0.05).ConclusionsFosinopril and amlodipine monotherapy were both effective in pediatric primary hypertension during a short-term follow-up. Fosinopril may be particularly effective in reducing BP in hypertensive patients of females, central obesity, IR, and hypo-HDL-cholesterolemia. These findings indicate that optimizing antihypertensive medication selection based on the individualized characteristics of children with hypertension may improve the efficacy of antihypertensive treatment.

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