title: Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation.
abstract: Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Tetsunobu
authors.initials: T
authors.lastname: Yamane
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakae
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takashima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tarutani
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D003329:Coronary Vasospasm / Q000235:genetics / Q000503:physiopathology; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000109:Acetylcholine; D001920:Bradykinin