Cilnidipine: A New Generation Ca<sup>2+</sup> Channel Blocker with Inhibitory Action on Sympathetic Neurotransmitter Release

Takahara, Akira

doi:10.1111/j.1755-5922.2009.00079.x

Cited by 75 publications

(71 citation statements)

References 125 publications

(144 reference statements)

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“…14,15 Cilnidipine, a new type of CCB that blocks the N-type calcium channel and the L-type calcium channel, is therefore thought to affect bone metabolism, possibly through the inhibition of both the sympathetic nervous system and the voltage-dependent calcium channel. [16][17][18][19] b-blockers are known to affect the relationship between the sympathetic nervous system and bone metabolism, leading to increased BMD. 20,21 Thus, in this study, we investigated the effects of cilnidipine on bone metabolism in comparison with those of amlodipine, an L-type dihydropyridine CCB, and carvedilol, a b-blocker that is known to reduce fracture risk though the inhibition of osteoclast activation via b2-adrenergic receptors, in an ovariectomy-induced rat osteoporosis model.…”

Section: Introductionmentioning

confidence: 99%

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

et al. 2011

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Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a b-blocker) because b-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.

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Section: Introductionmentioning

confidence: 99%

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

et al. 2011

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“…10 Meanwhile, previous studies have revealed that cilnidipine, an N-type and L-type CCB, is capable of blocking the two types of channels. 11 N-type calcium channels are members of the major calcium channel family, but they are fundamentally different from the other calcium channels and have highly distinctive calcium-regulation mechanisms. 12,13 N-type calcium channels are heteromultimeric complexes consisting of a pore-forming a1 subunit (a1B) and at least two auxiliary subunits, b and a2d, which modulate the function of the a1 subunit.…”

Section: Introductionmentioning

confidence: 99%

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

et al. 2010

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The inhibition of aldosterone activity is a useful approach for preventing the progression of cardiovascular and renal diseases in hypertensive patients. Although the results of our previous in vivo study suggested that N-type calcium channels may have a role in regulating plasma aldosterone levels, the direct relationship between N-type calcium channels and aldosterone production in adrenocortical cells has not been examined. In this study, the analysis of quantitative reverse transcription-PCR, western blotting, and immunocytological staining indicated the possible presence of N-type calcium channels in human adrenocortical cells (H295R cell line). Patch clamp analysis indicated that omega-conotoxin GVIA (CnTX), an N-type calcium channel inhibitor, suppressed voltage-dependent barium currents. During steroidogenesis, CnTX significantly reduced the transient calcium signaling induced by angiotensin II (Ang II) and partially prevented Ang II-induced aldosterone and cortisol formation with no significant influence on CYP11B2 and CYP11B1 mRNA expression. In addition, in a1B calcium channel subunits, knockdown significantly decreased Ang II-induced aldosterone formation with increments in CYP11B2 mRNA expression. We also investigated the inhibitory activities of some types of dihydropyridine calcium channel blockers (CCBs; cilnidipine: L-/N-type CCB, efonidipine: L-/T-type CCB, and nifedipine: L-type CCB), and these agents showed a dose-dependent inhibition effect on Ang II-induced aldosterone and cortisol production. Furthermore, only cilnidipine failed to suppress CYP11B1 expression in H295R cells. These results suggest that N-type calcium channels have a significant role in transducing the Ang II signal for aldosterone (and cortisol) biosynthesis, which may explain the mechanism by which N-type calcium channels regulate plasma aldosterone levels.

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“…11, 12 Abe conducted a study to compare the effect of cilnidipine against those of Amlodipine on BP, albuminuria. In hypertensive patients with mild to moderate chronic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Role of antihypertensives drugs on proteinuria in patients with chronic kidney disease and hypertension

Bala

Singh

Rupali

et al. 2017

Int J Basic Clin Pharmacol

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Background: Hypertension is the most prevalent cardiovascular disease and the relevant data suggest that the burden, risk factors and co-morbidities associated with the essential hypertension is increasing with every passing day. It is one of the major chronic diseases resulting in high mortality and morbidity in today’s world. Aim: The aim of the study was to compare effects of cilnidipine and amlodipine on the blood pressure (BP), heart rate and proteinuria among patients of hypertension with chronic kidney disease.Methods: 100 patients were included in this study. Patients were randomly assigned into two groups Group A and Group B (50 each). Group A: Patients received Cilnidipine (5-10mg/day). Group B: Patients received amlodipine (5-10mg/day).Results: No significant difference in SBP, DBP, MBP and proteinuria while comparing both the groups of patients taking cilnidipine and amlodipine at baseline i.e. 0 to 12 week, 12 to 24 weeks and 0 to 24 weeks. Cilnidipine caused decrease in HR 0 to 12 week (p value 0.001), 12 to 24 weeks (p value 0.001) and 0 to 24 weeks (p value 0.0001). Amlodipine had increased heart rate from baseline to 12 weeks (p value 0.0001), 12 to 24 weeks (p value 0.051) and 0 to 24 weeks (p value 0.001). No significant difference was seen in any biochemical readings.Conclusions: There was a significant change in all the parameters including BP, heart rate, proteinuria and other biochemical tests when they compared within the group but no significant difference while comparing both the groups.

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Cilnidipine: A New Generation Ca²⁺ Channel Blocker with Inhibitory Action on Sympathetic Neurotransmitter Release

Cited by 75 publications

References 125 publications

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

Role of antihypertensives drugs on proteinuria in patients with chronic kidney disease and hypertension

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Cilnidipine: A New Generation Ca2+ Channel Blocker with Inhibitory Action on Sympathetic Neurotransmitter Release

Cited by 75 publications

References 125 publications

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

Role of antihypertensives drugs on proteinuria in patients with chronic kidney disease and hypertension

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Cilnidipine: A New Generation Ca²⁺ Channel Blocker with Inhibitory Action on Sympathetic Neurotransmitter Release