Blocking T-Type Ca2+ Channels with Efonidipine Decreased Plasma Aldosterone Concentration in Healthy Volunteers

Okayama, Satoshi; Imagawa, Keiichi; Naya, Noriyuki; Iwama, Hajime; Somekawa, Satoshi; Kawata, Hiroyuki; Horii, Manabu; Nakajima, Takahito; Uemura, Shiro; Saito, Yoshihiko

doi:10.1291/hypres.29.493

Cited by 33 publications

(28 citation statements)

References 28 publications

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“…Efonidipine, another T-type CCB, has been shown to inhibit aldosterone synthesis and secretion in vitro, 9 as well as in both healthy subjects and patients with essential hypertension. 32,33 In this study, benidipine and amlodipine had no significant effect on clinic blood pressure, but both heart rate and plasma aldosterone level were significantly decreased in the benidipine treatment group. T-type CCBs inhibit renin secretion and renin gene expression in vivo, whereas L-type CCBs function as stimulators of the renin system.…”

Section: Discussionmentioning

confidence: 54%

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

et al. 2010

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Benidipine inhibits both L-and T-type Ca channels, and has been shown to dilate the efferent arterioles as effectively as the afferent arterioles. In this study, we conducted an open-label and randomized trial to compare the effects of benidipine with those of amlodipine on blood pressure (BP), albuminuria and aldosterone concentration in hypertensive patients with mild-tomoderate stage chronic kidney disease (CKD). Patients with BPX130/80 mm Hg, with estimated glomerular filtration rate (eGFR) of 30-90 ml min À1 per 1.73 m 2 , and with albuminuria430 mg per g creatinine (Cr), despite treatment with the maximum recommended dose of angiotensin II receptor blockers (ARBs) were randomly assigned to two groups. Patients received either of the following two treatment regimens: 2 mg per day benidipine, which was increased up to a dose of 8 mg per day (n¼52), or 2.5 mg per day amlodipine, which was increased up to a dose of 10 mg per day (n¼52). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was observed in both groups. The decrease in the urinary albumin to Cr ratio in the benidipine group was significantly lower than that in the amlodipine group. Although plasma renin activity was not different in the two groups, plasma aldosterone levels were significantly decreased in the benidipine group. Moreover, urinary Na/K ratio was significantly decreased in the benidipine group but remained unchanged in the serum. It may be concluded that benidipine results in a greater reduction of plasma aldosterone and albuminuria than amlodipine, and that these effects are independent of BP reduction.

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Section: Discussionmentioning

confidence: 54%

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

et al. 2010

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“…23,[29][30][31] Of interest, efonidipine possesses renal protective action via efferent arteriolar dilation, [17][18][19][20] the inhibition of Rho kinase 32 and, possibly, the inhibition of aldosterone activity. 33,34 Our present observations therefore imply a distinct therapeutic applicability of Ca channel blockers in CKD. 31,35 Of note, the present study showed that in patients with proteinuria at baseline, eGFR was lower than in non-proteinuric patients throughout the study period (Figures 4a and b, bottom).…”

Section: Discussionmentioning

confidence: 52%

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

et al. 2010

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on behalf of the JATOS Study GroupThis study evaluated the impact of renal function on cardiovascular outcomes in elderly hypertensive patients enrolled in the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive patients. The patients were randomly assigned to either a strict-treatment group (target systolic blood pressure (BP) o140 mm Hg, n¼2212) or a mild-treatment group (target systolic BP, 140 to o160 mm Hg, n¼2206), each with efonidipine (a T/L-type Ca channel blocker)-based regimens. Cardiovascular events (stroke, cardiovascular disease and renal disease) were evaluated during the 2-year follow-up period following the prospective randomized open-blinded end-point method. Estimated glomerular filtration rate (eGFR) was elevated throughout the trial period in both the strict-treatment (59.4-62 ml min À1 per 1.73 m 2 ) and the mild-treatment group (58.8-61.4 ml min À1 per 1.73 m 2 ). This tendency was also observed in diabetic patients and patients aged X75 years, with baseline eGFRo60 ml min À1 per 1.73 m 2 . Baseline eGFR (o60 vs. X60 ml min À1 per 1.73 m 2 ) had no definite relationship with the incidence of cardiovascular events, nor did the level of BP control. Proteinuria at the time of entry into the study, however, was significantly correlated with cardiovascular event rates (7.1%), an association that was more apparent in patients with eGFRo60 ml min À1 per 1.73 m 2 (8.2%). Furthermore, the event rate was more elevated in patients with greater declines in eGFR and was amplified when the baseline eGFR was o60 ml min À1 per 1.73 m 2 . In conclusion, the rates of decline of renal function and proteinuria constitute critical risk factors for cardiovascular events in elderly hypertensive patients, trends that are enhanced when baseline eGFR is diminished. Furthermore, the fact that efonidipine-based regimens ameliorate renal function in elderly hypertensive patients with chronic kidney disease may offer novel information on the mechanisms of cardiovascular protection.

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“…In harmony with this, clinical studies in healthy subjects and hypertensive patients have shown that the acute or the chronic administrations of T-type CCB lower plasma aldosterone levels (39,40). We have compared the effects of L-and T-type CCB efonidipine and L-type CCB amlodipine in patients with glomerulonephritis and observed that efonidipine reduces plasma aldosterone concentration as compared with amlodipine while the plasma angiotensin II concentrations were comparable (Figure 10) (35).…”

Section: Calcium Channel Blockers In Antihypertensive Drug Therapy Fomentioning

confidence: 69%

Blood Pressure Control in Patients with Glomerulonephritis

Ishimitsu¹

2011

An Update on Glomerulopathies - Clinical and Treatment Aspects

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Blocking T-Type Ca2+ Channels with Efonidipine Decreased Plasma Aldosterone Concentration in Healthy Volunteers

Abstract: Efonidipine can block both L-and T-type Ca2+ channels. In a previous in vitro study, we clarified that efonid-

Cited by 33 publications

References 28 publications

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

Benidipine reduces albuminuria and plasma aldosterone in mild-to-moderate stage chronic kidney disease with albuminuria

Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine

Blood Pressure Control in Patients with Glomerulonephritis

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