The Effect of Combination Therapy with an L/N-Type Ca2+ Channel Blocker, Cilnidipine, and an Angiotensin II Receptor Blocker on the Blood Pressure and Heart Rate in Japanese Hypertensive Patients: An Observational Study Conducted in Japan

Nagahama, Shinobu; Norimatsu, Takeo; Maki, Toshio; Yasuda, Masahiro; Tanaka, Shinsuke

doi:10.1291/hypres.30.815

Cited by 25 publications

(19 citation statements)

References 28 publications

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“…Cilnidipine blocks N-type as well as L-type calcium channels [4], and it has a variety of unique actions that are mediated by its N-type calcium channel blocking action, including suppression of sympathetic nerve activity [5,6,7], cardiovascular system protection [8,9,10,11] and kidney protection [12,13,14,15,16]. We also found that cilnidipine prevents the elevation of plasma renin activity (PRA) and the plasma angiotensin II (Ang II) level that occurs in spontaneously hypertensive rats (SHRs) [17] and a canine model of chronic atrioventricular block, which is known to exhibit ventricular electrical remodeling [18].…”

Section: Introductionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

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Background: Interrupting the renin-angiotensin system (RAS) with an angiotensin II receptor blocker (ARB) has been found to induce RAS overactivation. In this study, we investigated the effect of 2 calcium channel blockers (CCBs), cilnidipine (L-/N-type CCB) and amlodipine (L-type CCB), on the RAS activation induced by an ARB in a strain of spontaneously hypertensive rats (SHR/Izm, 10 weeks of age). Methods: Rats intravenously catheterized for blood collection were randomly divided into groups that were administered the vehicle, the ARB valsartan or valsartan combined with one of the 2 CCBs. Their blood and kidneys were collected 270 min after administration. Results: Valsartan increased the plasma angiotensin II (Ang II) level in a dose-dependent manner. Cilnidipine suppressed the increase in plasma renin activity and plasma Ang II levels induced by valsartan, but amlodipine did not. Combined administration of cilnidipine, but not amlodipine, and valsartan significantly reduced the noradrenaline content in the renal cortex. Conclusions: The results of this study suggest that the suppressive effect of cilnidipine on the valsartan-induced increase in RAS activity can be partly explained by its sympatholytic action mediated by N-type calcium channel blockade, and that combined administration of cilnidipine and valsartan might provide a synergistic therapeutic effect.

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Section: Introductionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

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“…In this study, the Cil group exhibited a declining trend in the NA level, which is an index of sympathetic nerve activity, although this decline was not statistically significant. Many reports have shown that Cil inhibited the hyperactivity of sympathetic nerves, despite L-type CCB activating the sympathetic nerve 19,20,24. However, the dose (Cil group: Cil, 2 mg/kg) used in this study might be too low to influence the NA level significantly because the effects observed in the previous animal studies were obtained using doses of at least 10 mg per day.…”

Section: Discussionmentioning

confidence: 78%

“…Cilnidipine (Cil), which blocks both N- and L-type calcium channels,17 has a variety of unique actions that are mediated by its actions as an N-type calcium channel blocker (CCB), including the suppression of sympathetic nervous overactivity,18–20 cardiovascular system protection,21–24 and kidney protection 25–29. In addition, we have found that Cil prevents the increases of PRA and plasma Ang II levels that occur in spontaneously hypertensive rats30 and in a canine model of a chronic atrioventricular block that exhibits ventricular electrical remodeling,31 despite the fact that the L-type CCB amlodipine (Aml) causes an increase in PRA and plasma Ang II levels due to its antihypertensive actions 30,32.…”

Section: Introductionmentioning

confidence: 99%

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

Mori

Aritomi

Niinuma

et al. 2014

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Cilnidipine (Cil), which is an L-/N-type calcium channel blocker (CCB), has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS) and the renin–angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml), which is an L-type CCB, with an angiotensin (Ang) II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val), Cil + Val, Aml + Val, or a vehicle (eight rats per group) for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin–Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1–7) to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1–7) levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II receptor type 1 antagonism. Thus, Cil may inhibit the progression of cardiorenal disease in type 2 diabetes patients by acting as an N-type CCB and inhibiting the aldosterone secretion and SNS activation when these drugs were administered in combination with an Ang II receptor blocker.

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“…Cilnidipine is an L/N type CCB. Its antihypertensive effect and safety have already been reported for ambulatory BP control and lowering of clinic and home BP (morning and evening) based on prospective post-marketing surveillance (PMS) studies of cilnidipine (ACHIEVE-ONE study) and as used in hypertensive patients concomitantly with angiotensin II receptor blockers (ARBs) (4)(5)(6). However, PMS study of cilnidipine in post-stroke hypertensive patients has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients: The CA-ATTEND study

Aoki

Hosomi

Nezu

et al. 2017

Clinical and Experimental Hypertension

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Blood pressure control is important in post-stroke hypertensive patients and antihypertensive treatment is recommended for such patients. Ca-channel blockers are recommended as the medications of choice for the treatment of post-stroke patients. Here, we report the results of a large-scale prospective postmarketing surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%, 69.0 ± 10.9 years) treated with cilnidipine, with regard to blood pressure control and adverse reactions. Cilnidipine treatment caused a decrease in both clinic and home blood pressures 2 months after the beginning of treatment, and the decreased blood pressure was maintained until the end of 12 months' observation. The proportion of patients in whom clinic blood pressure was well controlled (<140/90 mmHg) increased from 21.5% to 65.3% in cilnidipine treatment, with no differences in effectiveness among the various clinical subtypes of stroke. In total, 346 adverse events occurred, with an overall incidence of 8.9% (238 of 2667 patients). In the elderly group, specifically, a fall and a hip fracture each occurred in 1 (0.1%) patient. These results indicate that cilnidipine was effective in treating uncontrolled blood pressure and was well tolerated in Japanese post-stroke hypertensive patients in a real-world clinical setting. ARTICLE HISTORY

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The Effect of Combination Therapy with an L/N-Type Ca2+ Channel Blocker, Cilnidipine, and an Angiotensin II Receptor Blocker on the Blood Pressure and Heart Rate in Japanese Hypertensive Patients: An Observational Study Conducted in Japan

Cited by 25 publications

References 28 publications

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients: The CA-ATTEND study

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