Relationship between eNOS 894G>T polymorphism and the antihypertensive efficiency of two dihydropyridine calcium channel blocker drugs, azelnidipine and nitrendipine, in Chinese EH patients

Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.