Effects Of CGA On DOCA-salt Hypertension Rats Target Organ Protective Effects

Hypertension is the most cardiovascular disease,which affects approximately 26% of the adult population worldwide, and its prevalence is predicted to increase by 60% by 2025. Hypertension is one of the lifestyle-related diseases, and its onset and progression are due to the interplay of genetic predispositions and/or environmental factors(excessive salt intake, stress, etc.). In different animal models of hypertension, endothelial dysfunction has been shown to be associated with expression of ROS but decreased vascular NO bioavailability. There are several possible sources of reactive oxygen species(ROS), including NAD(P)H oxidase, xanthine oxidase, and uncoupling of endothelial nitric oxide synthase(e NOS). Based on previous studies, the regulation of ROS production is an important strategy for the treatment of hypertension. Chlorogenic acid(chlorogenic acid, CGA) is an important plant polyphenols, previous studies have found that it has antioxidant, antihypertensive effect, but also has to improve vascular remodeling(Vascular remodeling, VR) role, CGA can inhibit the activity of NADPH, is endogenous oxidative stress factor--NF-E2-related factor 2(Nuclear factor erythroid 2-related factor 2, Nrf2) activator.Although oxidative stress is known to many cardiovascular diseases, the development process of an important way, but clinical studies directly exogenous antioxidants failed to obtain the desired results, there is still some controversy. So, how can we enhance the endogenous antioxidant stress factors, Nrf2, PPARs have become a research focus in recent years.Previous studies have found that PPARs(peroxisome proliferator-activated receptors) has a protective effect on cardiovascular and blood pressure, and its mechanism of reducing the activity of NADPH and increasing expression of antioxidant enzymes in blood vessels. A number of NADPH isoforms are emerging as important components in the pathophysiology of hypertension. This suggests that a positive feedback loop exists among PPARs and Nrf2,the PPARs reduced expression is a direct effect of the lack of Nrf2.Therefore, we speculate that chlorogenic acid can increase the expression of Nrf2-PPARs activation pathway, promote endothelial cell NADPH generation, in order to prevent salt-sensitive hypertension, protect the kidneys, heart and other target organs.ObjectiveHigh blood pressure can cause damage to the heart, kidney and other organs, established deoxycorticosterone acetate(DOCA)-high-salt hypertensive rat animal model, its possible mechanism of kidney, heart and blood vessel damage in the DOCAsalt hypertensive. Materials and MethodsIn this study, Male Sprague-Dawley rats, 6–8weeks old and weighing 160–200 g, according to whether fed chlorogenic acid and injection DOCA, divided into control group, chlorogenic acid group, DOCA group, DOCA and chlorogenic acid group. After the four weeks intervention, measured the weight and blood pressure once a week, detection indicators are as follows.1.The systolic blood pressure(SBP) at the tail artery were measured using an automatic blood pressure monitoring system in awake and quiet rats.2.24-hour urine of DOCA-salt hypertensive rats was collected using a metabolic cage, and was determined by our hospital clinical laboratory Doctor.3.HE staining of kidney, heart and vascular sections of DOCA-salt hypertensive rats.4.Western blot detection of related signaling molecules in rat kidney tissue(Nrf2、PPARα、PPARβ、PPARγ、P22、P47、e NOS、 phospho-e NOS)by chlorogenic acid treatment. Results1.Dietary chlorogenic acid had no effect on blood pressure, but it can significantly improve the DOCA-salt hypertensive rats heart and vascular remodeling, prevented glomerular sclerosis. 2.Dietary chlorogenic acid increased kidney tissue Nrf2、PPARα 、 phosphorylation of e NOS protein expression and decrease P22、P47 protein expression in DOCA-salt hypertensive rats. Conclusions1.Chlorogenic acid had no effect on salt-sensitive hypertension, but it can prevent against renal damage,heart damage and vascular remodeling. 2.Chlorogenic acid reducing oxidative stress through the Nrf2-PPARs pathway.