Folic acid enhances the cardiovascular protective effect of amlodipine in renal hypertensive rats with elevated homocysteine

ABSTRACT

Objectives

To investigate the actions of amlodipine-folic acid (amlodipine-FA) preparation on hypertension and cardiovascular in renal hypertensive rats with hyperhomocysteinemia (HHcy), so as to provide experimental basis for clinical research of amlodipine folic acid tablets.

Methods

Rats model of renal hypertension with HHcy were established. The rats were randomly divided into groups of model, amlodipine, folic acid (FA) and amlodipine-FA of various dosages. Normal rats were used as normal control group. Blood pressure, Hcy as well as plasma NO, ET-1 and hemodynamics were assayed. Histological alterations of heart and abdominal aorta were also examined.

Results

Compared with the normal group, blood pressure, plasma Hcy, and NO of the rats in model group were significantly increased, while the plasma ET-1 was decreased. Compared with the normal group, the animals in the model group had reduced cardiac function, thickened wall of the aorta and narrowed lumen. In FA group and amlodipine group, the rat plasma NO was increased while ET-1 was decreased, the protective effect of amlodipine-FA group on endothelial cells was further enhanced. In amlodipine group, the rat hemodynamics (LVSP, LVEDP and ±dp/dt_max, et al.) and vascular damage were significantly reduced, while in amlodipine-FA group, the heart function were further improved, and myocardial and vascular hypertrophy were significantly reduced.

Conclusions

As compared to amlodipine alone, amlodipine -FA can lower both blood pressure and plasma Hcy, significantly enhancing vascular endothelial function to protect the heart and blood vessel in renal hypertensive rats with HHcy.

KEYWORDS:

• Amlodipine
• folic acid
• hypertension
• homocysteine
• cardiovascular protection

Author contributions

Conceived and designed the experiments: Pr. Guangliang Chen and Haipeng Liu; Performed the experiments: Li li, Xiaohui Tong and Zebing Ma; Performed the pathological examination: Lei Lv and Zebin Ma; Analysed the data: Tong Xiaohui; Wrote the manuscript: Tong Xiaohui Tong and Pr.Guangliang Chen.

Additional information

Funding

This work was supported by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” [Grant Number: [2012] 52–401013], the National Major Scientific and Technological Special Project for “Safety evaluation of clinical study of amlodipine folic acid tablets” [Grant Number: 2018ZX09739010–006].