Tetrahydrobiopterin improves coronary endothelial function, but does not prevent coronary spasm in patients with vasospastic angina.
Reduced bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, and the resulting decrease in NO in the coronary circulation may be involved in the pathogenesis of coronary spasm. The present study investigated the effects of BH4 on the vascular response to acetylcholine (ACh) in 28 patients with vasospastic angina (VA) using quantitative angiography. After recording the vascular responses to ACh (3 and 30 microg/min), either BH4 (1 mg/min) or saline was infused into the coronary artery for 2 min before and during a subsequent infusion of ACh. With the 3 microg/min dose of ACh, BH4 attenuated the ACh-induced decrease in coronary diameter in both the nonspastic segments (-1.1 +/- 2.2% ACh vs 6.0 +/- 2.8% ACh+BH4) and spastic segments (-6.3 +/- 2.7% ACh vs 2.9 +/- 2.7% ACh+BH4), but did not influence the ACh-induced coronary spasm at 30 microg/min (-57.3 +/-2.4% ACh vs -55.3 +/- 2.4% ACh+BH4). In the control patients, saline did not influence either the spastic or nonspastic vasoconstrictor responses to ACh. Acute administration of BH4 improves coronary endothelial function, but does not prevent coronary spasm in patients with VA.
Fukuda
Yukihiro
Y
The First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. yfukuda@hiroshima-u.ac.jp
Teragawa
Hiroki
H
Matsuda
Keiji
K
Yamagata
Togo
T
Matsuura
Hideo
H
Chayama
Kazuaki
K
D000109:Acetylcholine / Q000494:pharmacology; D000787:Angina Pectoris / Q000503:physiopathology*; D000975:Antioxidants / Q000627:therapeutic use*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003329:Coronary Vasospasm / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012016:Reference Values; D012107:Research Design; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D001708:Biopterins; D009569:Nitric Oxide; C003402:sapropterin; D000109:Acetylcholine