## 4 Discussion
HO-1 protects endothelial cells and cardiomyocytes as an antioxidant [33]. HO-1 also directly inhibits cardiomyocyte hypertrophy and reduces the ratio of left ventricular weight to body weight. At the same time, the antihypertensive effect of HO-1 is also related to its ability to improve endothelial cell function [34]. The level of plasma ADM in patients with hypertension is higher than that of persons without hypertension. The mRNA of ADM and RAMP2 in rats with myocardial infarction and heart failure increased in both atrial and ventricular muscle. The mRNA levels of ADM and RAMP2 in infarcted and non-infarcted myocardium increased. In some disease states, such as shock, congestive heart failure and obstructive nephropathy, the expression levels of ADM and RAMP2 genes can be upregulated todifferent degrees in cardiovascular tissue, which plays an important compensatory protective role in the cardiovascular system [35]. Further studies have also showed that the expression levels of ADM and RAMP2 mRNA in heart and blood vessels of hypertensive rats were significantly higher than those in rats without hypertension, and similar results were obtained in this study [36]. NO is an effective vasodilator that can maintain normal tension in the blood vessels. The enzyme that catalyses the biosynthesis of NO is called NOS, and it is divided into nNOS, eNOS and iNOS based on the cell or tissue source of the prototype enzyme [37]. When hypertension occurs with decreasing NOS, vascular-dependent hypertension, the endothelial relaxant response becomes weaker. In the normal physiological state of the body, iNOS is generally not expressed, but eNOS (eNOS and nNOS) in endothelial cells continuously synthesizes a small amount of NO to regulate vascular tension and blood pressure [38]. Exposure to an endotoxin in pathological conditions involving various cytokines can induce the production of macrophages and iNOS gene expression in white blood cells; as a result, NO is produced to inhibit endotoxin and cytokines, and its hypotensive effect is strong and is involved in the pathological process [39]. NO produced by eNOS relaxes blood vessels, inhibits proliferation of vascular smooth muscle cells, inhibits platelet aggregation and maintains normal vascular tension and arterial blood pressure. However, in hypertension, atherosclerosis and other pathological conditions, the NO produced by eNOS cannot maintain the normal tension of blood vessels on its own; iNOS can activate and produce relatively large amounts of NO, so blood pressure does not increase malignancy [40; 41]. In this study, OPO could also increase nNOS and eNOS expression levels and reduce iNOS expression in hypertensive rats. Citrus juice consumption in China has been increasing, and juice processing generates millions of tons of peel every year. Citrus peel has long been recognized as a rich source of flavonoids that are important to human health and nutrition. Several studies have reported the effects of different flavonoids or peel phenolic extract on hypertension. Short-term and long-term administration of hesperidin and glucosyl hesperidin showed hypotensive effects on spontaneous hypertensive rats, and this effect was associated with nitric oxide-mediated vasodilation [42; 43]. The phenolic extract from grapefruit peels was shown to inhibit \(\alpha\)-amylase-, \(\alpha\)-glucosidase- and angiotensin-I-converting enzymes in a dose-dependent manner [44]. In another study, a grapefruit peel extract was able to decrease coronary vascular resistance and the mean arterial pressure in a Langendorff isolated and perfused heart model [45]. Nevertheless, most of these studies used raw extract of citrus peel. In this study, the prophylactic effect of cold-pressed peel oil of long-leaf orange on hypertension was studied. Because of the hydrophobicity, the composition of the oil is much simpler than that of the whole peel extract; HPLC analysis showed that most of the non-volatile bioactive components were polymethoxyflavones.