Effects of Melatonin and Pycnogenol on Small Artery Structure and Function in Spontaneously Hypertensive Rats

Abstract

Abstract-It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentrationresponse curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects. Key Words: endothelial function Ⅲ melatonin Ⅲ Pycnogenol oxidative stress R eactive oxygen species (ROS) are generated as byproducts of cellular respiration and other metabolic processes and may contribute to oxidative damage. 1,2 The ROS family includes several molecules that have divergent effects on cellular function, namely, regulation of cell growth and differentiation, modulation of extracellular matrix production and breakdown, inactivation of NO, and stimulation of protein kinases and proinflammatory genes. 3-5 Importantly, some of these actions are associated with pathological changes in cardiovascular tissues. 6 In cardiovascular disease, increased ROS production leads to endothelial dysfunction, increased vascular contractility, vascular smooth muscle cell growth and apoptosis, monocyte migration, lipid peroxidation, inflammation, and increased deposition of extracellular matrix proteins, all processes contributing to vascular damage. 7 ROS may be important in the development and maintenance of hypertension, in terms of excess production of oxidants, decreased NO bioavailability, and decreased antioxidant capacity in the vasculature and kidneys. 6,7 Hypertension may contribute to structural and functional al...

Reactive oxygen species and vascular biology: implications in human hypertension

“…175 Recent studies demonstrated that pycnogenol, a polyphenol and melatonin, protect the vasculature against oxidative damage, independently of blood pressure changes. 178,179 Some of the beneficial effects of classical antihypertensive agents such as -adrenergic blockers, angiotensin-converting enzyme inhibitors, AT 1 receptor antagonists and Ca 2+ channel blockers may be mediated, in part, by decreasing vascular oxidative stress. [180][181][182][183][184] These effects have been attributed to direct inhibition of NADPH oxidase activity and to intrinsic antioxidant properties of the drugs.…”

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

“…This is important because even though other agents are reported to effectively inhibit MPO activity in vitro, their toxic side effects reduce their usefulness in vivo. For example, large doses of melatonin have been used to improve vasodilatation in hypertensive rats ( 68 ). However, the melatonin treatments also increased the number of apoptotic cells in the vessel wall of the hypertensive rats ( 68 ).…”

“…For example, large doses of melatonin have been used to improve vasodilatation in hypertensive rats ( 68 ). However, the melatonin treatments also increased the number of apoptotic cells in the vessel wall of the hypertensive rats ( 68 ). Likewise, when cholesterol-fed rabbits were treated with 4-aminobenzoic acid hydrazide, which is highly effective for inhibiting MPO activity in vitro, the treatments actually increased intimal hyperplasia by over 43% ( 69 ).…”

Use of Black Seed (Nigella Sativa L.) Oil in the Management of Hypertensive and Hyperlipidemic Individuals of District Muzaffarabad, Azad Kashmir, Pakistan

“…Antioxidants contained melatonin (Flavonoids) can effectively be used in reducing blood pressure, lipid profile, body weight and plasma glucose (Hussein et al, 2007). Antioxidants have strong impact of reducing the blood pressure which is also supported by a recent study (Rezzani et al, 2010) that described the protective role of antioxidants against the initiation of atherosclerosis in hypertensive animal model. Houghton et al (1995) reported that the biologically active constituents of N. sativa had potent quenching capabilities for free radicals.…”