Long-term calcium antagonist treatment of human hypertension with mibefradil or amlodipine increases sympathetic nerve activity

Lindqvist, M.; Kahan, Thomas; Melcher, A.; Ekholm, Mikael; Hjemdahl, Paul

doi:10.1097/hjh.0b013e3280104dba

Cited by 41 publications

(42 citation statements)

References 41 publications

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“…However, another report suggested that amlodipine treatment increases sympathetic nerve activity. 34 In this study, we could not confirm a sympathetic nerve activitydecreasing effect of amlodipine in Dahl salt-sensitive rats.…”

Section: Discussioncontrasting

confidence: 49%

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

et al. 2011

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Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5 mg kg À1 , bolus injection) or azelnidipine (0.1 mg kg À1 , bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0 mg kg À1 per day) and azelnidipine (3.0 mg kg À1 per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0 mg kg À1 per day) or azelnidipine (3.0 mg kg À1 per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity.

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Section: Discussioncontrasting

confidence: 49%

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

et al. 2011

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“…It has been thought that shortacting CCBs activate the sympathetic nervous system through the baroreflex mechanism, which offsets their favorable effect on IS, such as vasodilation. However, despite its longacting property, amlodipine does not improve IS (11), probably because it activates the sympathetic nervous system (28). On the other hand, the long-acting dihydropyridine CCB, cilnidipine, which suppresses norepinephrine release from sympathetic nerve endings by acting on N-type calcium channel receptors, has been shown to improve IS in subjects with essential hypertension (10) and fructose-fed rats (FFR) (18).…”

Section: Sympathetic Activitymentioning

confidence: 99%

Effects of Antihypertensive Drugs and Exercise Training on Insulin Sensitivity in Spontaneously Hypertensive Rats

et al. 2008

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We examined the effects of antihypertensive drugs, exercise training, and combinations thereof on insulin sensitivity (IS), and the association between this relation and sympathetic activity, muscle fiber composition, and capillary density in spontaneously hypertensive rats (SHR). Six-week-old male SHR were allocated to 7 groups: a control group (C), and groups treated with azelnidipine (Aze) (a calcium channel blocker),

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“…More recently, it has been suggested that mibefradil's antihypertensive and vasodilatory effects are mediated by inhibition of L-type VGCC (Moosmang et al 2006). Mibefradil is still the subject of clinical trials where it demonstrates beneficial effects compared to LTCC channel blockers due to its lack of negative chronotropic effects (Lindqvist et al 2007). Although the role of T-type VGCC in regulating blood pressure remains controversial, research into selective T-type channel blockers with potential use in hypertension treatment still continues (Bui et al 2008).…”

Section: Mibefradilmentioning

confidence: 98%

Pharmacology of Voltage-Gated Calcium Channels in Clinic

Lacinová

Lichvarova

2013

Pathologies of Calcium Channels

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The diversity of voltage-gated calcium channels (VGCC) allows precise time-and voltage-dependent regulation of calcium ions entry into cells. Individual calcium channel subtypes participate in the initiation of neuronal action potential and repetitive action potential firing; in cardiac pacemaking and signal conduction; in shaping an action potential plateau; and in action potential repolarization. Calcium entry through VGCC is necessary for cardiac and smooth muscle cell contraction. Since disrupted regulation of calcium homeostasis accompanies various pathologies, the complex pattern of regulation of cell physiology by VGCC makes them an attractive target for pharmaceutical agents. The most common pathologies treated with VGCC blockers are cardiovascular diseases, especially hypertension, angina, and tachycardia. In addition, calcium channels have been identified as targets of some antiepileptic and anesthetic drugs. More recently, specific VGCC blockers were introduced in the treatment of chronic pain, and these have also proved beneficial as support therapy in neurodegenerative diseases and cognitive impairment. IntroductionVoltage-gated calcium channels (VGCC) are a family of voltage-gated ion channels which are far less diverse than the voltage-gated potassium channel family-in respect to the number of representatives and also to the diversity of the current waveform. It is, however, much more diverse than the voltage-gated sodium channel family in respect to its kinetics and voltage dependencies of channel gating. Since the calcium current is ionic, it flows through the VGCC and modulates the dynamics

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Long-term calcium antagonist treatment of human hypertension with mibefradil or amlodipine increases sympathetic nerve activity

Abstract: Mibefradil and amlodipine treatment increase global sympathetic nerve activity similarly during long-term treatment, despite opposite effects on heart rate. Increases in myocardial velocities suggest concomitant cardiac sympathetic activation.

Cited by 41 publications

References 41 publications

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity

Effects of Antihypertensive Drugs and Exercise Training on Insulin Sensitivity in Spontaneously Hypertensive Rats

Pharmacology of Voltage-Gated Calcium Channels in Clinic

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