## 1 Introduction  
The flavonoids in citrus fruits are a major class of secondary metabolites that have significant biological activities. While the exact roles of these stress response and defensive compounds in plant tissue remain unclear [1], the broad-spectrum bioactivities and functionalities of citrus flavonoids, and in particular polymethoxyflavones (PMFs), in mammalian systems have been intensely studied and well-documented in recent years. PMFs display strong anti-allergic, antioxidant, antibacterial, anti-proliferative, anti-inflammatory and anticancer activities [2; 3; 4; 5]. They have also shown inhibitive, preventative and anti-proliferative activities against melanoma cells both in vitro and in vivo [6; 7; 8; 9]. Epidemiological studies have indicated that ingestion of nobiletin, a citrus PMF, is associated with a reduced risk of certain types of cancer and chronic disease [10]. Members of the PMF family have a 2-phenyl-\(\gamma\)-pyrone skeleton, and each member differs in the number, type and positions of methoxy substituents in their core structure. Because of the hydrophobicity of methoxy groups relative to hydroxyl groups, PMFs are more lipophilic than polyhydroxylated flavonoids, such as quercetin, luteolin, scutellarein and naringenin. Therefore, the PMFs have higher membrane permeabilities and are readily absorbed into the human blood stream [11], thus increasing their bioavailability. Likewise, because of their high lipophilicity, almost all PMFs in citrus fruits occur in the peel flavedo, the peripheral surface layer that contains the peel oil, paraffin wax and other hydrophobic components. Nitric oxide can regulate blood vessel tension and reduce blood pressure. Nitric oxide is also a key material for the prevention of cardiovascular and cerebrovascular diseases, such as hypertension [12]. N\({}^{\omega}\)-nitro-\(L\)-arginine (\(L\)-NNA) can be used as an NOS inhibitor, and it can inhibit nitric oxide generation, causing high blood pressure [13]. Based on this characteristic, \(L\)-NNA is often used in animal experiments for inducing high blood pressure. NOS inhibitors can reduce endothelium-dependent relaxation induced by various vasodilatation factors [14]. A large dose of NOS inhibitor can dramatically reduce the generation of nitric oxide in vascular endothelial in a short time, which promotes the proliferation of vascular smooth muscle cells and noticeably changes the structure of vascular tissues [15]. This process can damage endothelial function and elevate arterial blood pressure, which may further limit nitric oxide synthesis in endothelial cells for maintaining high blood pressure [16]. Angiotensin II is also used for experimental hypertension models [17; 18; 19]. Angiotensin II can cause over-activation of the renin-angiotensin-aldosterone system, inducing hypertension, and nitric oxide can prevent different kinds of hypertension [20]. Orange (_Citrus sinensis_) is the most cultivated and consumed citrus fruit around the world. The value of orange peel oil for food and beverage flavorings, perfumery and aromatherapy has long been recognized. Cold-pressed orange peel oil, which has the best quality, only accounts for approximately 0.6% of the total fruit by weight; however, it contains more than half the amount of the total polymethoxyflavones present in the whole fruit, which makes it the most bioactive fraction of the orange fruit [18]. In the present study, we used a rat model of NOS inhibitory-type hypertension caused by \(L\)-NNA to determine the preventative and alleviating effects of PMF-rich orange peel oil. The blood pressures were determined and the molecular markers in the blood and tissues of the rats analyzed to explore the underlying mechanisms of orange peel oil (OPO) activity. The NO (nitric oxide) and MDA (malonaldehyde) contents in serum, heart, liver, kidney and stomach and the ET-1 (endothelin-1), CGRP (calcium gene-related peptide) and VEGF (vascular endothelial growth factor) contents in serum were determined.