# Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases
## 5 Lycopene in Cardiovascular Diseases (CVDs)
### Hypertension and Lycopene  
A systolic blood pressure of more than 140 mmHg or a diastolic blood pressure of more than 90 mmHg, or both, is characterized as systemic arterial hypertension (HT), often known as high blood pressure [226]. As the silent killer, promoted by low-density lipoprotein cholesterol and smoking, it remains the third-leading cause of mortality from cardiovascular disease. Hypertension is also a major cause of stroke and renal failure. Hypertension is associated to oxidative stress and inflammatory processes [227; 228]. Chronic hypertension can cause renal failure, left ventricular hypertrophy (LVH), chronic heart disease (CHD), heart failure (HF), peripheral vascular disease, stroke, and retinopathy. Figure 5: Demonstration of vessel protection by the application of lycopene that caused the inhibition of AGE and RAGE production. It also leads to vasodilation, protection of proteins, DNA, lipids, and mitochondrial damage, by boosting the antioxidant activity. Improved endothelial function is reached by increasing nitric oxide (NO) bioavailability, ensuring positive changes in the lipid profile and healthy arteries, and preventing atherosclerosis. The pathophysiology of hypertension is highly complex and multifactorial. A complex interaction of environmental and pathophysiological variables that impact many systems have been reported to contribute to the development of hypertension. According to one opinion, as described by some research reports, hypertension is developed by the influence of oxidative stress. Oxidative stress makes changes in the structure and function of blood vessels by lowering the nitric oxide (NO), resulting in endothelial dysfunction and vascular cell proliferation, migration, and apoptosis, all of which promote hypertension [229]. The blood pressure-lowering effects of ROS scavengers, antioxidants, and NOX inhibitors also support the role of oxidative stress in the pathogenesis of hypertension [230]. NO is produced by endothelial cells that operate in coordination with prostacyclin to inhibit the production of adhesion molecules and aggregation of platelets. Hence, in the absence of NO, the components and mechanisms of atherosclerosis are promoted. The pathogenesis of hypertension is also well described by the renin-angiotensin system (RAS), which also provides the potential targets for the therapies against hypertension [230]. Angiotensin, a precursor of angiotensin, is produced in the liver, while renin is the enzyme produced by the juxtagglomerural cells of the kidneys, which catalyzes the first step in the processing of angiotensin into angiotensin I [231]. The angiotensin-converting enzyme (ACE), mainly produced in the lungs, is responsible for the conversion of angiotensin I into angiotensin II [232], which interacts with corresponding receptors and leads to the production of multiple biological molecules including ADH (antidiuretic hormone), aldosteroneone, and potent agents for vesorestiction from smooth muscle cells of vessels, adrenal, and pituitary glands. The combined effects of all these developments include the reabsorption of sodium and water by kidney, decrease in the amount of urine, narrowing of blood vessels, and subsequent onset of hypertension [233] (Figure 6). Lycopene reduces oxidative stress indirectly increases nitric oxide (NO) generation in the endothelium, acting as an antioxidant and decreases blood pressure. After 6 weeks of tomato extract supplementation, a significant reduction in both systolic and diastolic blood pressure was found in 54 patients suffering from moderate hypertension, already using ACE inhibitors or calcium channel blockers, indicating a contribu  
Figure 6: A presentation of antihypertensive effects of lycopene by inhibition of ACE (angiotensin enzyme) and through an antioxidant activity to inhibit the action of ROS on the linings of the blood vessels, resulting in the improvement of nitric oxide levels and the functioning of endothelium.