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: Tetsunobu Yamane, Tetsuya Matsumoto, Ichiro Nakae, Hiroyuki Takashima, Yasuhiro Tarutani, Shinji Tamaki, Minoru Horie
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 29 Issue 6 Pg. 417-22 (Jun 2006) ISSN: 0916-9636 [Print] England
• PMID: 16940704 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Endothelium-Dependent Relaxing Factors
• Aryldialkylphosphatase
• PON1 protein, human
• Acetylcholine
• Bradykinin

Topics

• Acetylcholine (pharmacology)
• Adult
• Aged
• Aged, 80 and over
• Angina Pectoris
• Aryldialkylphosphatase (genetics, physiology)
• Bradykinin (pharmacology)
• Coronary Circulation (drug effects, genetics, physiology)
• Coronary Vasospasm (genetics, physiopathology)
• Coronary Vessels (anatomy & histology, drug effects, pathology)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects, physiology)
• Endothelium-Dependent Relaxing Factors (pharmacology)
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Vasoconstriction (drug effects)
• Vasomotor System (drug effects, physiology)