Disease relevance of Atelec

• Thus, in patients with essential hypertension, cilnidipine suppressed cardiac sympathetic overactivity and amlodipine had a little suppressive effect [1].
• Cilnidipine was thus found to show an additive effect with valsartan and thereby caused a reduction in albuminuria in type II diabetics [2].
• CONCLUSION : Cilnidipine not only prevented, but reversed, the severe renal hemodynamic and glomerular dynamic changes, including apoptosis and glomerular cellular proliferation, in l-NAME/SHR-exacerbated nephrosclerosis [3].
• In conclusion, cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca++-channel in rat dorsal root ganglion neurons [4].
• These results suggest that cilnidipine did not cause hypotension-evoked tachycardia deficiency by depression of cardiac L-type channels but by sympathetic N-type channels blockade [5].

High impact information on Atelec

• Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension [1].
• Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion from differentiated PC12 cells [6].
• The objective of this trial was to evaluate the effect of reducing albuminuria in type II diabetic patients with a combination therapy consisting of valsartan plus cilnidipine versus monotherapy with valsartan [2].
• OBJECTIVE : To determine the responses of the new dihydropyridine N- and L-type calcium antagonist, cilnidipine, on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathology in an Nomega-nitro-l-arginine methylester spontaneously hypertensive rat (l-NAME/SHR) model of nephrosclerosis [3].
• Cilnidipine dose-dependently inhibited depolarization- and Ca2+-induced contractions of rat aortic rings, with an IC50 of 10 nmol/l at 10 min [7].

Chemical compound and disease context of Atelec

• Gender, age, body mass index, duration of hypertension, target organ damage of hypertension, and BP and heart rate (HR) were not significantly different between cilnidipine and nifedipine groups, and both systolic (SBP) and diastolic BP (DBP) were significantly decreased after treatment in both groups [8].
• Pretreatment with cilnidipine (0.3, 1.0 and 3.0 microg/kg, i.v.), which decreased mean blood pressure by 5 to 31 mm Hg, inhibited the changes in heart rate and plasma norepinephrine concentration induced by bilateral carotid artery occlusion, whereas it had no effect on vagal nerve stimulation-induced bradycardia [9].
• DOCA-vehicle rats showed a significant increase in the wall-to-lumen ratio, perivascular fibrosis and myocardial fibrosis, with all these parameters being significantly improved by cilnidipine [10].
• Comparison of haemodynamic responses to cilnidipine and nicardipine in an experimental model of acute congestive heart failure [11].
• Sixty patients with mild essential hypertension aged more than 39 years were randomly allocated to two groups to receive cilnidipine (10 mg; n = 30) or quinapril (10 mg; n = 30) [12].

Biological context of Atelec

• RESULTS : Cilnidipine significantly reduced mean arterial pressure, total peripheral resistance and renal vascular resistance, while increasing effective renal blood flow and glomerular filtration rate (P < 0.01) in l-NAME/SHR [3].
• The data also suggest that cilnidipine binds to sites independent of those controlling voltage-sensing and channel kinetics in these alpha(1B) subunits [13].
• Thus, bedtime, but not morning, dosing with cilnidipine significantly reduces nocturnal blood pressure [14].
• RESULTS: Cilnidipine significantly decreased the 24 h blood pressure by 6.5 +/- 1.7 mm Hg systolic (mean +/- s.e.mean; P < 0.01) and 5.0 +/- 1.1 mmHg diastolic (P < 0.01), whereas cilnidipine did not change heart rate or any indices of power spectral components [15].
• The metabolic interaction between beneficial lipid changes and fibrinolysis will be of value to better our understanding of the antiatherogenic effects of cilnidipine treatment in hypertensive patients [16].

Anatomical context of Atelec

• We conclude that cilnidipine represents an extremely slow-acting DHP that targets multi-subunit L-type channels, but not PKC in arterial smooth muscle [7].
• To address this issue, we studied the effects of cilnidipine on multi-subunit, C-class L-type Ca2+ channels in rat aortic A7r5 cells, as well as on Ca2+ channel (L-type) alpha1C-b and (T-type) alpha1G subunits in the Xenopus oocyte expression system [7].
• Cilnidipine, a slow-acting Ca(2+) channel blocker, induces relaxation in porcine coronary artery: role of endothelial nitric oxide and [Ca(2+)](i) [17].
• Cilnidipine is a dual blocker of L-type voltage-gated Ca(2+) channels in vascular smooth muscle and N-type Ca(2+) channels in sympathetic nerve terminals that supply blood vessels [17].
• CONCLUSIONS: Cilnidipine is effective as a once-daily antihypertensive agent and causes little influence on heart rate and the autonomic nervous system in patients with mild to moderate essential hypertension [15].

Associations of Atelec with other chemical compounds

• Cilnidipine depressed dopamine release both from NGF-treated and untreated PC12 cells in a concentration-dependent manner [6].
• Furthermore, white coat effects on systolic BP and HR were significantly lower after treatment in the cilnidipine group compared with the nifedipine group [8].
• After the cold pressor test, increases in EP (35+/-17 to 44+/-25 pg/ml; p<0.05) and BTG (40+/-13 to 49+/-22 ng/ml; p<0.01) and a decrease in ADPEC50 (32+/-26 to 27+/-24 micromol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment [18].
• At the level of the vasculature cilnidipine reduced the neurotransmitter release to electrical stimulation in both the noradrenaline spillover model and in the model of the rat isolated tail artery, respectively [19].
• In contrast, administration of nicardipine was associated with significant increases in heart rate and cardiac contractility but that of cilnidipine was not [11].

Gene context of Atelec

• Effects of cilnidipine on nitric oxide and endothelin-1 expression and extracellular signal-regulated kinase in hypertensive rats [10].
• Cilnidipine (1 microM) significantly inhibited the expression of TGF-beta1 mRNA in VSMC from SHR but not in cells from WKY rats [20].
• A negative correlation was found between low-density lipoprotein cholesterol and t-PA antigen levels after cilnidipine treatment [16].
• AIM: To study the metabolism of cilnidipine and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of cilnidipine in human liver microsomes in vitro [21].
• In neurons pretreated with Cal plus omegaAgTx, cilnidipine induced a potent inhibition of the N-type current, but was unable to block the residual Ba++ current [4].

Analytical, diagnostic and therapeutic context of Atelec

• METHODS: Ten inpatients with mild to moderate essential hypertension (four men and six women; age: 44-64 years) underwent a drug-free period for 7 days and a treatment period with cilnidipine 10 mg orally for another 7 days, in a randomized crossover study [15].
• The blocking effects of cilnidipine and other dihydropyridines on L-type cardiac Ca2+ channels (I(Ca,L)) and N-type sympathetic Ca2+ channel currents (I(Ca,N)) were studied using a whole-cell patch-clamp technique [5].
• Urinary protein significantly decreased after 6 months in cilnidipine group (- 0.21+/- 0.11 g/day, - 36%, p< 0.01), whereas it did not change in control group (+ 0.01+/- 0.15 g/day, 0.4%, ns) [22].
• Cilnidipine (0.5 or 1.0 microg/kg/min, i.v.) or saline (i.v.) was administered from 30 min before ischemia to 30 min after reperfusion [23].
• Ambulatory blood pressure monitoring in patients with essential hypertension treated with a new calcium antagonist, cilnidipine [24].

References