Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats

Takatsu, Miwa; Hattori, Takuya; Murase, Tatsuro; Ohtake, Masafumi; Kato, Mayumi; Nashima, Keigo; Nakashima, Chieko; Takahashi, K.; Ito, Hiromi; Niinuma, Kazumi; Aritomi, Shizuka; Murohara, Toyoaki; Nagata, Kazuya

doi:10.1097/hjh.0b013e3283567645

Cited by 24 publications

(29 citation statements)

References 52 publications

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“…In the present study, UUO rats were treated with cilnidipine or amlodipine at the dose of 3 mg·kg Ϫ1 ·day Ϫ1 for 14 days. Several previous reports demonstrated that cilnidipine and amlodipine had a lowering effect of blood pressure to a similar extent at the dose used in this study (3 mg·kg Ϫ1 ·day Ϫ1 ) in hypertensive rats (12,25,26). Previous pharmacological study also demonstrated that cilnidipine and amlodipine inhibited L-type Ca channel current to a similar extent using a whole cell patch-clamp technique (29).…”

Section: Discussionsupporting

confidence: 68%

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Mishima

Maeshima

Miya

et al. 2013

American Journal of Physiology-Renal Physiology

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type Ca 2ϩ channels are densely distributed in sympathetic nerves that innervate renal tubules. However, the role of N-type Ca 2ϩ channels in renal fibrosis remains unknown. To address this issue, we examined the difference between the effects of amlodipine (an L-type Ca 2ϩ channel blocker) and cilnidipine (a dual L/N-type Ca 2ϩ channel blocker) on fibrotic changes using a rat unilateral ureteral obstruction (UUO) model. The expression of both L-type and N-type Ca 2ϩ channels was significantly upregulated in UUO kidneys compared with that in contralateral kidneys. There were no significant differences in mean blood pressure among the rats tested. Both amlodipine and cilnidipine significantly attenuated fibrotic changes in UUO kidneys. The antifibrotic effect of cilnidipine was more potent than that of amlodipine. Amlodipine as well as cilnidipine reduced type III collagen deposition, ␣-smooth muscle actin (␣-SMA) expression, and interstitial cell proliferation. In addition, cilnidipine significantly reduced deposition of type I collagen and macrophage infiltration in UUO kidneys. With the use of in vivo bromodeoxyuridine labeling, label-retaining cells (LRCs) were identified as a population of tubular cells that participate in epithelial-mesenchymal transition after UUO. Some LRCs migrated into the interstitium, expressed ␣-SMA and vimentin, and produced several extracellular matrixes in UUO kidneys. The number of interstitial LRCs was significantly decreased by cilnidipine but not amlodipine. These data suggest that N-type Ca 2ϩ channels contribute to multiple steps of renal fibrosis, and its blockade may thus be a useful therapeutic approach for prevention of renal fibrosis.N-type calcium channel; renal fibrosis; unilateral ureteral obstruction; epithelial-mesenchymal transition THE RENAL SYMPATHETIC NERVES innervate the tubules, the vessels, and the juxtaglomerular granular cells of the kidney (5). Renal sympathetic nerve activation reduces urinary sodium and water excretion by increasing renal tubular water and sodium reabsorption throughout the nephron. It also decreases renal blood flow and glomerular filtration rate by constricting the renal vasculature and activates the renin-angiotensin system (RAS) by stimulating renin release from juxtaglomerular granular cells. Conversely, angiotensin II stimulates sympathetic nerve activity through central mechanisms and by facilitating adrenergic neurotransmission at the sympathetic nerve terminal, thus suggesting significant interactions between renal sympathetic nerves and the RAS in the control of renal function (4). N-type Ca 2ϩ channels are densely distributed in the sympathetic nervous system and play a predominant role in neurotransmitter release from the nerve endings of sympathetic neurons (8). In patients with chronic renal diseases, increased sympathetic nerve activity and plasma renin activity are observed (10), thus suggesting that sympathetic nerve activity via N-type Ca 2ϩ channels is involved in renal injury. Renal fibrosis is the common end point o...

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Section: Discussionsupporting

confidence: 68%

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Mishima

Maeshima

Miya

et al. 2013

American Journal of Physiology-Renal Physiology

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“…In Dahl salt-sensitive rat model, Cilnidipine reduces relative wall thickness more than Amlodipine [48], Cilnidipine significantly improved LVMI than that of control CCBs group and Cilnidipine reduces LV mass index significantly after 3 months of the initiation of treatment whereas Amlodipine do so 6 months after the initiation of treatment, also corroborates with the result of present study [49,50].…”

Section: Discussionsupporting

confidence: 91%

Comparison of Efficacy of Amlodipine and Cilnidipine on Left Ventricular Hypertrophy amongst Hypertensive Patients

Sarkar¹,

Srivastava²,

Mohanty³

2017

J Hypertens

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“…Both body weight and food intake were monitored on a weekly basis. Systolic blood pressure (SBP) was also measured weekly with animals in the conscious state by indirect tail‐cuff plethysmography (BP‐98A; Softron, Tokyo, Japan) . An oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT) were performed as described previously …”

Section: Methodsmentioning

confidence: 99%

Effects of ramelteon on cardiac injury and adipose tissue pathology in rats with metabolic syndrome

Uchinaka

Kawashima

Sano

et al. 2018

Annals of the New York Academy of Sciences

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Melatonin regulates circadian rhythms but also has antioxidative and anti-inflammatory effects that ameliorate metabolic disorders. We investigated the effects of the selective melatonin agonist ramelteon on cardiac and adipose tissue pathology in the DahlS.Z-Lepr /Lepr (DS/obese) rat, a model of metabolic syndrome (MetS). Rats were treated with a low (0.3 mg/kg per day) or high (8 mg/kg per day) dose of ramelteon from 9 to 13 weeks of age. Ramelteon treatment at either dose attenuated body weight gain, left ventricular fibrosis, and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or insulin resistance. Although ramelteon did not affect visceral white adipose tissue (WAT) mass, it attenuated inflammation and downregulated insulin signaling in this tissue. In contrast, ramelteon reduced fat mass, adipocyte hypertrophy, and inflammation, and ameliorated impaired insulin signaling in subcutaneous WAT. In addition, ramelteon attenuated adipocyte hypertrophy, downregulated mitochondrial uncoupling protein 1, and upregulated 11β-hydroxysteroid dehydrogenase type 1 expression in interscapular brown adipose tissue (BAT). In summary, ramelteon treatment attenuated obesity and cardiac injury, improved insulin signaling in visceral and subcutaneous WAT, and inhibited the whitening of BAT in rats with MetS.

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Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats

Cited by 24 publications

References 52 publications

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Comparison of Efficacy of Amlodipine and Cilnidipine on Left Ventricular Hypertrophy amongst Hypertensive Patients

Effects of ramelteon on cardiac injury and adipose tissue pathology in rats with metabolic syndrome

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Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats

Cited by 24 publications

References 52 publications

Involvement of N-type Ca2+channels in the fibrotic process of the kidney in rats

Involvement of N-type Ca2+channels in the fibrotic process of the kidney in rats

Comparison of Efficacy of Amlodipine and Cilnidipine on Left Ventricular Hypertrophy amongst Hypertensive Patients

Effects of ramelteon on cardiac injury and adipose tissue pathology in rats with metabolic syndrome

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Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats

Involvement of N-type Ca²⁺channels in the fibrotic process of the kidney in rats