Supplementation with the Symbiotic Formulation Prodefen® Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats

Abstract

In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen® (108 colony forming units/day, 4 weeks). Prodefen® diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen®. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen®, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen® caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen® could be an interesting non-pharmacological approach to ameliorate hypertension.

Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

“…In the present study, we aimed to evaluate the role of NO alterations in fetal programming of hypertension induced by maternal undernutrition during gestation, which we have previously demonstrated in adult male offspring [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34],…”

“…This effect was sex-dependent and may be related to a higher superoxide anion production and/or to a lower elimination by antioxidant enzyme systems, since we have evidence that male rats of MUN model are deficient in antioxidants [ 33 , 34 ]. The smaller antioxidant capacity of MUN males was also evidenced by the low Nrf2, a factor that regulates adaptive response to oxidative stress promoting the transcription of antioxidant enzymes [ 4 ], and is downregulated in hypertensive animals [ 26 ]. The excess superoxide anion may be due to increased NADPH oxidase in the arterial wall, as we have demonstrated in mesenteric arteries from MUN males [ 41 ].…”

The cardioprotective effects of secoisolariciresinol diglucoside (flaxseed lignan) against cafeteria diet-induced cardiac fibrosis and vascular injury in rats: an insight into apelin/AMPK/FOXO3a signaling pathways

“…Hyperlipidemia and obesity are commonly associated with oxidative stress, which is capable of modifying vascular tone by impeding NO bioavailability and signaling ( Čolak and Pap, 2021 ). During the oxidative stress state, excessive production of ROS reduces the bioactivity of NO due to its rapid oxidative inactivation by the ROS superoxide anion ( Mendez-Albinana et al, 2022 ). In alignment, it was observed in the current work that CAFD supplementation induced a significant reduction of NO circulating levels.…”

Protection by -Biotics against Hypertension Programmed by Maternal High Fructose Diet: Rectification of Dysregulated Expression of Short-Chain Fatty Acid Receptors in the Hypothalamic Paraventricular Nucleus of Adult Offspring

“…Studies performed in hypertensive humans and animal models of hypertension have reported that supplementation with different prebiotic, probiotic, or synbiotic agents enhances acetate, butyrate, and propionate production, leading to the amelioration of hypertension [ 72 , 73 ]. In addition, increases in acetic, butyric, and propionic acids in plasma have been demonstrated after ingestion of FOS in different animal models, including SHR [ 74 , 75 ]. At the same time, long-term administration of L .…”