Differential effects of calcium-channel blockers on vascular endothelial function in patients with coronary spastic angina.
BACKGROUND
The effects of the 3 classes of L-type calcium-channel blockers (CCBs) on vascular endothelial function have not been clarified in patients with coronary vasospasm.


RESULTS
Twenty-five normotensive patients (age 64.0+/-1.4 years) with coronary vasospasm were randomly treated for 3 months with benidipine, diltiazem, and verapamil, which belong to the dihydropyridine, benzothiazepine, and phenylalkylamine classes of CCBs, respectively. Endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent nitroglycerin-induced dilatation in the brachial arteries, and plasma cyclic guanosine 3',5'-monophosphate (cGMP), a nitric-oxide-related product, were assessed before and after treatment. At baseline, the patients with vasospasm had significantly lower FMD as compared with normal subjects (n=8). Blood pressure did not differ among the 3 groups before and after treatment. Benidipine significantly increased FMD (from 4.7+/-0.6 to 7.4+/-1.1%, P<0.05) and plasma cGMP levels. In contrast, neither diltiazem nor verapamil affected FMD and cGMP levels. None of the treatments affected nitroglycerin-induced dilatation.


CONCLUSIONS
Benidipine, but not diltiazem or verapamil, improves endothelial dysfunction beyond blood pressure lowering effects in patients with coronary vasospasm. Upregulation of the nitric oxide - cGMP system by benidipine may partly contribute to the improvement. The dihydropyridine class may be more beneficial for vascular endothelial function than the non-dihydropyridine classes of CCBs.
Miwa
Yoichi
Y
Department of Internal Medicine, National Hospital Organization Kobe Medical Center, Kobe, Japan. yomiwa-circ@umin.ac.jp
Masai
Hiroyuki
H
Shimizu
Masatoshi
M
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D003329:Coronary Vasospasm / Q000188:drug therapy* / Q000503:physiopathology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000009:adverse effects / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine; D014700:Verapamil; D004110:Diltiazem