Renal-Protective Effect of T- and L-Type Calcium Channel Blockers in Hypertensive Patients: An Amlodipine-to-Benidipine Changeover (ABC) Study

Ohishi, Mitsuru; Takagi, Takashi; Ito, Norihisa; Terai, Minako; Tatara, Yuji; Hayashi, Norihiro; Shiota, Atsushi; Katsuya, Tomohiro; Rakugi, Hiromi; Ogihara, Toshio

doi:10.1291/hypres.30.797

Cited by 43 publications

(41 citation statements)

References 28 publications

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“…16 -18 In a changeover study, benidipine (L-and T-type antagonist) caused a larger reduction in blood pressure and proteinuria compared with L-type treatment using amlodipine. 16 The observation of superior renoprotective effects with a combined L-and T-type treatment is in agreement with demonstration of a vasoconstrictor effect of T-type channels on efferent arterioles in animal studies.…”

supporting

confidence: 83%

“…16 -18 In a crossover study, benidipine (L-and T-type antagonist) caused a larger reduction in blood pressure and proteinuria compared with L-type treatment using amlodipine, 16 and benidipine favorably affects renal function in patients with essential hypertension compared with amlodipine. 18 These studies suggest a clinical benefit of benidipine over amlodipine as an antihypertensive drug because of a renoprotective effect.…”

Section: Discussionmentioning

confidence: 99%

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Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

et al. 2011

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Abstract-Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Ϫ8 mol/L. The T-type antagonist mibefradil inhibited the potassium-induced constriction with large variations between patients. Interestingly, the P/Q-type antagonist, -agatoxin IVA, inhibited significantly the contraction with 24% at 10 Ϫ9 mol/L. In conclusion L-, P/Q, and T-type channels are expressed in human renal blood vessels, and L-and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human vasculature is a novel mechanism for the regulation of renal blood flow and suggests that clinical treatment with calcium blockers might affect vascular reactivity also through P/Q-type channel inhibition.

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supporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

et al. 2011

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“…In another study, it was reported that a higher urinary protein excretion (Po0.0001), lower GFR (P¼0.0011) and the presence of diabetes (P¼0.0284) correlated with the reduction of urinary proteins when the treatment with amlodipine was replaced with treatment with benidipine. 13 The difference between our study and the CARTER study could be attributed to the large number of diabetic nephropathy cases included in our study. Moreover, the baseline proteinuria and sCr levels reflected a greater deterioration in patients in our study than in those of the CARTER study.…”

Section: Discussionmentioning

confidence: 60%

“…In renal tissues, the L-type calcium channels are present only in the afferent arterioles, whereas the N-type and T-type calcium channels are localized in both efferent and afferent arterioles. 12,13 Amlodipine is a representative CCB that is used widely all over the world; it blocks the L-type calcium channel and dilates the afferent arterioles to a higher degree than the efferent arterioles. 14,15 However, it has recently been reported that both a dual L-/N-type CCB cilnidipine and an L-/T-type CCB efonidipine exhibit a greater antiproteinuric effect than does amlodipine.…”

Section: Introductionmentioning

confidence: 99%

“…13,19 The mechanism by which benidipine exerts renoprotective and antihypertensive effects in hypertensive patients with CKD has not been elucidated. The objective of this study is to determine the effects of benidipine on BP and renoprotection in Japanese hypertensive patients with moderate-to-advanced stages of CKD (stages 3-5) and who are already being treated with a maximum recommended dose of ARBs.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

et al. 2009

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Benidipine, an L-and T-type calcium channel blocker, dilates both efferent and afferent arterioles and reduces glomerular pressure. Thus, it may exert renoprotective effects. We conducted an open-labeled, randomized trial to compare the blood pressure (BP)-lowering effect and antiproteinuric effect of benidipine with those of amlodipine in hypertensive patients with moderate-to-advanced-stage chronic kidney disease (CKD) (stages 3-5). These patients were already being administered the current maximum recommended doses of angiotensin receptor blockers (ARBs). Patients with BP X140/90 mm Hg, despite treatment with the maximum recommended dose of ARBs, were randomly assigned to two groups. The patients received either of the following treatment regimens: 4 mg day À1 of benidipine, which was increased up to a dose of 16 mg day À1 (B group; n¼24), and 2.5 mg day À1 of amlodipine, which was increased up to a dose of 10 mg day À1 amlodipine (A group; n¼23). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was seen in both groups. The decrease in the urinary protein to creatinine ratio in the B group was significantly lower than that in the A group. Benidipine exerted antiproteinuric effect to a greater extent than did amlodipine, even in patients with diabetic nephropathy. We conclude that the addition of benidipine, rather than amlodipine, ameliorates urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs. Therefore, we propose a combination therapy with benidipine and ARBs, even for patients with moderate-to-advanced-stage CKD.

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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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Renal-Protective Effect of T- and L-Type Calcium Channel Blockers in Hypertensive Patients: An Amlodipine-to-Benidipine Changeover (ABC) Study

Cited by 43 publications

References 28 publications

Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3–5 chronic kidney disease

Pharmacology of Voltage-Gated Calcium Channels in Clinic

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