Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries

Abstract

Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy.

Dietary docosahexaenoic acid supplementation prevents the formation of cholesterol oxidation products in arteries from orchidectomized rats

“…Nitric oxide is also a critical molecule in vascular function, and the inhibition of endothelial NO-synthase by COPs has been described [ 52 , 66 ], which is also in agreement with the decreased NO formation observed in aorta [ 9 ] and mesenteric artery [ 10 ] from orchidectomized rats. Although the decrease of NO production by COPs seems to be demonstrated, studies addressing the influence of COPs in the vascular function have shown contradictory results, since inhibition [ 67 , 68 ] or no modification [ 69 , 70 ] of endothelial-dependent vasodilation by 7-KC and 7α-OH-cholesterol have been reported.…”

“…These discrepancies could be attributed to differences in the animal model used, since the maintenance period of gonadectomy determines the induced alterations [ 8 , 58 ]. However, it is important to emphasize that the experimental model used in this study is the same as that used in our two previous studies [ 9 , 10 ] and provides relevant information about the key role of the COPs in the orchidectomy-induced modifications of factors, additional to ROS, which regulate vascular function.…”

“…Likewise, different COPs induced the expression of COX-2 [ 63 ] and the release of prostaglandin E 2 [ 64 ] and prostaglandin J 2 [ 65 ], considered as pro-inflammatory events. Accordingly, it has been described that orchidectomy also leads to a pro-inflammatory environment by increasing prostanoid production in rat aorta [ 6 , 8 , 9 ] and mesenteric arteries [ 7 , 8 , 10 ] most likely as a consequence of increased oxidative stress produced during the experimental conditions.…”

“…Thus, the levels of COPs were near to those measured in control rats fed the control diet. Interestengly, the DHA-supplemented diet restored the increased contents of COPs induced by orchidectomy, similarly how it restores the lipid profile, and the redox and inflammatory status altered in this particular condition [ 9 , 10 ]. These results are in agreement with the cardioprotective effects of DHA widely reported through its anti-inflammatory [ 31 ] and anti-oxidant activities [ 33 – 35 ].…”

“…It has been demonstrated that sex hormones regulate vascular function since sex hormones deprivation alters the release, function and cell signaling pathways of endothelial factors that could lead to vascular dysfunction. Thus, previous studies from our research group have shown that orchidectomy increased ROS production [ 3 , 4 ] and prostanoids release [ 5 – 7 ], while the production of nitric oxide [ 8 ] and the antioxidant capacity [ 9 – 10 ] were reduced.…”