Document Detail

A new-generation N/L-type calcium channel blocker leads to less activation of the renin-angiotensin system compared with conventional L type calcium channel blocker.
MedLine Citation:
PMID:  20625317     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Calcium channel blocker (CCB) is one of the most useful antihypertensive agents. However, the activation of the renin-angiotensin system (RAS) is an unfavorable characteristic. N-type calcium channel is thought to be involved in catecholamine's release. Accordingly, N/L-type CCB has a probability of less activation of the RAS. We substantiated the hypothesis that N/L-type CCB, cilnidipine, leads to less activation of the RAS compared with conventional L-type CCB, amlodipine.
DESIGN: Randomized, cross-over study.
SETTING: Outpatient study.
PARTICIPANTS: Participants were 110 hypertensive patients [male/female 46/64, age 66.3 ± 10.8 years, systolic blood pressure (SBP)/diastolic blood pressure (DBP) 161.8 ± 16.9/92.9 ± 12.4 mmHg, s-Cr 0.77 ± 0.32 mg/dl, plasma renin activity (PRA) 0.65 ± 0.63 ng/ml per h, angiotensin I (AngI) 70.5 ± 77.3 pg/ml, angiotensin II (AngII) 5.2 ± 3.9 pg/ml, plasma aldosterone concentration (PAC) 76.3 ± 35.9 pg/ml, urinary albumin excretion (UAE) 108.1 ± 284.2 mg/gCr]. Amlodipine besilate or cilnidipine was administered for 12 weeks in a cross-over manner as a monotherapy with an intention-to-treat fashion by titrating doses. Final doses of amlodipine besilate and cilnidipine were 6.6 ± 2.7 and 13.7 ± 5.1 mg/day, respectively.
MAIN OUTCOME MEASURES: Changes in blood pressure, PRA, AngI, AngII, PAC, UAE of baseline and each end of amlodipine besilate and cilnidipine administration.
RESULTS: Results were as follows (amlodipine vs. cilnidipine): SBP/DBP (mmHg): 135.2 ± 11.7/79.8 ± 9.6 vs. 136.7 ± 13.2/79.5 ± 10.9, P = 0.22/0.74; PRA (ng/ml per h): 1.16 ± 1.03 vs. 0.95 ± 0.78, P < 0.01; AngI (pg/ml): 155.0 ± 306.4 vs. 101.8 ± 92.0, P < 0.05; AngII (pg/ml): 12.0 ± 12.3 vs. 7.1 ± 4.5, P < 0.001; PAC (pg/ml): 81.6 ± 37.9 vs. 74.3 ± 36.2, P < 0.05; UAE (mg/gCr): 145.4 ± 424.5 vs. 58.8 ± 125.1, P < 0.05. Thus, in spite of the comparable blood pressure reductions, each level of components of the RAS at cilnidipine administration was significantly lower than those at amlodipine. Apart from this, UAE at cilnidipine administration was also significantly lower than that at amlodipine.
CONCLUSION: It is suggested that cilnidipine leads to less activation of the RAS compared with amlodipine for the first time in human clinical patients and therefore cilnidipine might be expected to be superior in organ protection in addition to the antialbuminuric effect.
Tadashi Konoshita; Yasukazu Makino; Tomoko Kimura; Miki Fujii; Shigeyuki Wakahara; Kenichiro Arakawa; Isao Inoki; Hiroyuki Nakamura; Isamu Miyamori;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  2156-60     Citation Subset:  IM    
Third Department of Internal Medicine, Fukui University School of Medicine, Eiheiji, Fukui 910-1193, Japan.
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MeSH Terms
Albuminuria / physiopathology
Aldosterone / blood
Amlodipine / pharmacology*,  therapeutic use
Angiotensin I / blood
Angiotensin II / blood
Blood Pressure / drug effects,  physiology
Calcium Channel Blockers / pharmacology*,  therapeutic use
Cross-Over Studies
Dihydropyridines / pharmacology*,  therapeutic use
Dose-Response Relationship, Drug
Hypertension / blood,  drug therapy,  physiopathology*
Middle Aged
Renin / blood
Renin-Angiotensin System / drug effects*,  physiology
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Dihydropyridines; 11128-99-7/Angiotensin II; 132203-70-4/cilnidipine; 52-39-1/Aldosterone; 88150-42-9/Amlodipine; 9041-90-1/Angiotensin I; EC

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