Lactobacillus group and arterial hypertension: A broad review on effects and proposed mechanisms.

Hypertension is the leading risk factor for cardiovascular diseases and is associated with intestinal dysbiosis with a decrease in beneficial microbiota. Probiotics can positively modulate the impaired microbiota and impart benefits to the cardiovascular system. Among them, the emended Lactobacillus has stood out as a microorganism capable of reducing blood pressure, being the target of several studies focused on managing hypertension. This review aimed to present the potential of Lactobacillus as an antihypertensive non-pharmacological strategy. We will address preclinical and clinical studies that support this proposal and the mechanisms of action by which these microorganisms reduce blood pressure or prevent its elevation.

Lactate inhibited sodium intake in dehydrated rats.

Recent studies have suggested that glial cells, especially astrocytes, are involved in balanced hydromineral modulation. In response to increased extracellular Na+ concentration, astrocytic Nax channels are activated, promoting lactate production and release. Furthermore, previous in vitro studies have suggested that lactate and hypertonic Na + solution activate SFO GABAergic neurons involved in the salt-appetite central pathways. Here, we evaluated the role of lactate in dehydration-induced sodium and water intake. To this end, intracerebroventricular microinjection (icv) of l-lactate or α-cyano-4-hydroxycinnamic acid (α-CHCA, MCT lactate transporter inhibitor) was performed in rats subjected to 48 h of water deprivation (WD) and 1 h of partial rehydration after 48 h of WD (WD-PR). The rehydration protocol was used to distinguish the mechanisms of thirst and sodium appetite induced by WD. Then, water and sodium (0.3 M NaCl) intake were evaluated for 2 h. Our results showed that central α-CHCA induced an increase in sodium preference in WD rats. Furthermore, central lactate increased water intake but reduced sodium intake in WD-PR animals. In contrast, central lactate transporter inhibition did not change water or sodium intake in WD-PR rats. Our results suggest that lactate is involved in inhibitory mechanisms that induce sodium intake avoidance in dehydrated rats.

Central interaction between nitric oxide, lactate and glial cells to modulate water and sodium intake in rats.

The "astrocyte-to-neuron lactate shuttle" (ANLS) mechanism is part of the central inhibitory pathway to modulate sodium intake. An interaction between the GABAergic neurons and nitric oxide (NO) in the subfornical organ (SFO) in salt-appetite inhibition has been suggested. In addition, NO is a key molecule involved in astrocytic energy metabolism and lactate production. In the present study, we hypothesized there is an interaction between astrocytic lactate and central NO to negatively modulate water and sodium intake through the ANLS mechanism. The results showed that central Nω-nitro-L-arginine methyl ester (L-NAME, NO-synthase inhibition) induced an increase in water and sodium intake. These responses were attenuated by previous central microinjection of fluorocitrate (FCt, a reversible glial inhibitor). Interestingly, L-NAME-induced water and sodium intake were also decreased by previous microinjection of lactate but did not change after inhibition of the ANLS mechanism by α-cyano 4-hydroxycinnamic acid (α-CHCA), an inhibitor of the MCT lactate transporter. Our results suggest a central interaction between NO, glial cells, and lactate to modulate water and sodium intake.

Potentially Probiotic Limosilactobacillus fermentum Fruit-Derived Strains Alleviate Cardiometabolic Disorders and Gut Microbiota Impairment in Male Rats Fed a High-Fat Diet.

High-fat diet (HFD) consumption is a risk factor for dyslipidemias, insulin resistance, and arterial hypertension linked with gut dysbiosis. Probiotic administration has been suggested as a safe therapeutic strategy for gut microbiota modulation and treatment and/or prevention of cardiometabolic disorders. Here, we assessed the effects of a potentially probiotic formulation containing strains of the Limosilactobacillus (L.) fermentum 139, 263, and 296 on the cardiometabolic disorders and gut microbiota derangements provoked by the HFD consumption. Male Wistar rats were allocated into control diet (CTL, n = 6), HFD (n = 6), and HFD receiving L. fermentum formulation (HFD-LF, n = 6) groups for 4 weeks. L. fermentum formulation (109 colony-forming unit (CFU)/ml of each strain) was daily administered by oral gavage. After 4-week follow-up, biochemical measurements, blood pressure (BP), heart rate (HR), sympathetic tone, and gut microbiota composition were evaluated. HFD consumption for 4 weeks increased lipid profile, insulin resistance, sympathetic tone, and blood pressure and impaired gut microbiota composition in male rats. Administration of L. fermentum formulation improved the gut microbiota composition, lipid profile, insulin resistance, autonomic dysfunction, and BP in rats fed with a HFD. Administration of a potentially fruit-derived probiotic formulation of L. fermentum strains improved gut microbiota composition and alleviated hyperlipidemia, insulin resistance, and sympathetic hyperactivity and increased BP in rats fed a HFD. Our findings may encourage the development of randomized controlled trials to assess the effects of L. fermentum treatment in subjects with cardiometabolic disorders.

Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats.

The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic) neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN). Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry) within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.