title: A -786T>C polymorphism in the endothelial nitric oxide synthase gene reduces serum nitrite/nitrate levels from the heart due to an intracoronary injection of acetylcholine.
abstract: We identified a -786T>C polymorphism in the eNOS gene, and this polymorphism was strongly associated with coronary spasm. The present study aimed to elucidate whether the -786T>C polymorphism or acetylcholine (ACh)-induced coronary spasm affects serum nitrite/nitrate (NOx) levels. The study population comprised three groups: (i) 26 patients without coronary spasm in the left anterior descending coronary artery (LAD) with the T/T genotype (group A); (ii) 20 patients with coronary spasm in the LAD with the T/T genotype (group B); and (iii) 16 patients with coronary spasm in the LAD with the C/T genotype (group C). Paired blood samples were obtained from the coronary sinus (CS) and the aortic tract (Ao) before and after an intracoronary injection of ACh. Serum NOx and plasma lactate levels were measured. The delta NOx level was calculated as the serum concentration of NOx in the CS minus that in the Ao. We compared lactate extraction ratios (LERs) and delta NOx levels between the three groups. The LERs after the provocation test in groups A, B and C were 18.9+/-2.4%, -0.5+/-3.9% and -13.5+/-4.2%, respectively. The LER in group C was significantly lower than in group B. The delta NOx levels after the provocation test in groups A, B and C were 11.5+/-1.7 micromol/l, 10.4+/-3.5 micromol/l and -2.1+/-4.8 micromol/l, respectively. The delta NOx levels in group C were significantly lower (P<0.05). Although the NOx level was significantly increased after the provocation test in group A (P<0.05), the NOx level was significantly decreased after the provocation test in group C (P=0.001). In group B, the provocation test did not significantly change the delta NOx level. In conclusion, the -786T>C polymorphism reduces the NOx level from the heart due to an intracoronary injection of ACh, and thereby predisposes the patients to severe coronary spasm.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamamuro
authors.forename: Makoto
authors.initials: M
authors.lastname: Shono
authors.forename: Satoru
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Nishijima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasue
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D003329:Coronary Vasospasm / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009573:Nitrites / Q000097:blood; D011110:Polymorphism, Genetic; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine