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.
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.


METHODS
Randomized, cross-over study.


METHODS
Outpatient study.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Konoshita
Tadashi
T
Third Department of Internal Medicine, Fukui University School of Medicine, Eiheiji, Fukui 910-1193, Japan. konosita@u-fukui.ac.jp
Makino
Yasukazu
Y
Kimura
Tomoko
T
Fujii
Miki
M
Wakahara
Shigeyuki
S
Arakawa
Kenichiro
K
Inoki
Isao
I
Nakamura
Hiroyuki
H
Miyamori
Isamu
I
D000368:Aged; D000419:Albuminuria / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D000804:Angiotensin II; D017311:Amlodipine; D000450:Aldosterone; D000803:Angiotensin I; C065927:cilnidipine; D012083:Renin