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.

Limosilactobacillus fermentum prevents gut-kidney oxidative damage and the rise in blood pressure in male rat offspring exposed to a maternal high-fat diet.

Oxidative stress along the gut-kidney axis is a risk factor for developing arterial hypertension in offspring from dams fed a high-fat diet. Considering the antioxidant capacity of probiotic strains, this study evaluated the effects of a daily multistrain formulation with Limosilactobacillus fermentum 139, 263, and 296 on blood pressure (BP), renal function, and oxidative stress and along the gut-kidney axis in male offspring from dams fed a high-fat high-cholesterol (HFHC) diet during pregnancy and lactation. Dams were fed a diet control or HFHC diet during pregnancy and lactation. At 100 days of age, part of the male offspring from dams fed a HFHC diet received Limosilactobacillus fermentum formulation for 4 weeks (HFHC + Lf) daily. After the 4-week intervention, BP (tail-cuff plethysmography) and urinary and biochemical variables were measured. In addition, malondialdehyde levels, enzymatic activities of superoxide dismutase, catalase, glutathione-S-transferase, and nonenzymatic antioxidant defense (thiols content) were measured in the colon and renal cortex. Male offspring from dams fed a HFHC had increased blood pressure, impaired renal function, and oxidative stress along the gut-kidney axis. Administration of Limosilactobacillus fermentum reduced systolic, diastolic, and mean blood pressure levels and alleviated renal function impairment and oxidative stress along the gut-kidney axis in male offspring from dams fed a HFHC diet. Administration of Limosilactobacillus fermentum formulation attenuated programmed hypertension in the HFHC group through oxidative stress modulation along the gut-kidney axis.

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.

Maternal exposure to high-fat and high-cholesterol diet induces arterial hypertension and oxidative stress along the gut-kidney axis in rat offspring.

AIMS: Evaluate the effects of maternal high fat and high cholesterol (HFHC) diet consumption on blood pressure (BP), renal function and oxidative stress along the gut-kidney axis in male and female rat offspring. MATERIALS AND METHODS: Pregnant rats were fed with a control (CTL) or HFHC diet during pregnancy and lactation. At 90 days, BP was assessed by tail-cuff plethysmography, and urinary and biochemical variables were measured. Biomarkers for oxidative stress, enzymatic antioxidant defense (activity of superoxide dismutase-SOD, catalase, and glutathione-S-transferase-GST) and nonenzymatic antioxidant defense (thiols content) were evaluated in the colon and renal cortex. KEY FINDINGS: Male and female offspring from dams fed with a HFHC diet presented increased BP when compared to their respective CTL group. Male offspring from dams fed with HFHC diet showed reduced GST activity and thiols content in the colon, reduced SOD activity in the renal cortex and decreased urinary creatinine excretion when compared to the CTL group. Regarding female offspring, catalase activity and thiols content were reduced in the colon when compared to CTL group. Although lipid peroxidation had been increased in the renal cortex of HFHC female offspring, the CAT and SOD enzymatic antioxidant acitivities (CAT and SOD) were increased in the renal cortex of female offspring when compared with male offspring; and the renal function was not impaired by maternal HFHC diet consumption. SIGNIFICANCE: HFHC diet during pregnancy and lactation induces sex-specific oxidative stress along the gut-kidney axis in offspring, which might induce renal dysfunction and arterial hypertension in later life.

Short- and long-term effects of maternal dyslipidaemia on blood pressure and baroreflex sensitivity in male rat offspring.

Maternal dyslipidaemia is a predisposing factor for arterial hypertension in male rat offspring at adulthood. This study was designed to investigate the short- and long-term effects of maternal dyslipidaemia on blood pressure (BP) and baroreflex control in male rat offspring. Animals were obtained from mothers who received a dyslipidaemic (DLP, n = 7) or control (CTL, n = 7) diet during pregnancy and lactation. At 30 and 90 days of age, arterial pressure (AP), heart rate (HR) and baroreflex function were evaluated. In addition, spectral analysis of the systolic AP, diastolic AP, mean AP, HR, and spontaneous baroreflex were assessed. Data were expressed as mean ± SEM and Student's t-test was used for comparison among groups, with statistical significance considered to be P < .05. At 30 days of age, male offspring had similar BP, HR and preserved baroreflex sensitivity. In addition, low frequency (LF) oscillation, high frequency (HF) oscillation and LF/HF ratio of AP and HR were similar in juvenile rats. At 90 days of age, male offspring from dyslipidaemic dams had augmented BP (P < .05) when compared to CTL group. Adult male rats from dyslipidaemic dams had a reduction in baroreflex control (P < .05) in comparison to CTL rats. The present study indicates that offspring from dams fed on a dyslipidaemic diet during pregnancy and lactation do not show alteration in blood pressure and baroreflex control in early life, but display a decline in baroreflex control and hypertension in adulthood.

Acute Treatment with Lauric Acid Reduces Blood Pressure and Oxidative Stress in Spontaneously Hypertensive Rats.

The effects of acute administration of lauric acid (LA), the most abundant medium-chain fatty acid of coconut oil, on blood pressure, heart rate and oxidative stress were investigated in spontaneously hypertensive rats (SHR). Intravenous doses of LA reduced blood pressure in a dose-dependent fashion (1, 3, 4, 8 and 10 mg/kg) in both SHR and Wistar Kyoto rats. LA (10-8 to 3 × 10-3 M) induced vasorelaxation in isolated superior mesenteric artery rings of SHR in the presence (n = 7) or absence (n = 8) of functional endothelium [maximum effect (ME) = 104 ± 3 versus 103 ± 4%]. After exposure to KCl (60 mM), LA also induced concentration-dependent vasorelaxation (n = 7) compared to that under Phe-induced contraction (ME = 113.5 + 5.1 versus 104.5 + 4.0%). Furthermore, LA-induced vasorelaxation in vessels contracted with S(-)-BayK8644 (200 nM), a L-type Ca2+ channel agonist (ME = 91.4 + 4.3 versus 104.5 + 4.0%, n = 7). Lastly, LA (10-3 M) reduced NADPH-dependent superoxide accumulation in the heart (18 ± 1 versus 25 ± 1 MLU/min/µg protein, n = 4, p < 0.05) and kidney (82 ± 3 versus 99 ± 4 MLU/min/µg protein, n = 4, p < 0.05). Our data show that LA reduces blood pressure in normotensive and hypertensive rats. In SHR, this effect might involve Ca+2 channels in the resistance vessels and by its capability of reducing oxidative stress in heart and kidneys.

Participation of the TRP channel in the cardiovascular effects induced by carvacrol in normotensive rat.

Carvacrol has been described as an agonist/antagonist of different transient receptor potential (TRP) channels and voltage-dependent calcium channels (Cavs). The aim of this study was to evaluate the role of Cav and TRP channels following carvacrol stimulation. Initially, in mesenteric artery rings carvacrol relaxed phenylephrine-induced contractions. Furthermore, carvacrol inhibited contraction elicited by CaCl2 in depolarizing nominally without Ca2+ medium and antagonized the contractions induced by S(-)-Bay K 8644 and inhibited Ca2+ currents indicating the inhibition of Ca2+ influx through L-type Cav. Additionally, carvacrol antagonized the contractions induced by CaCl2 in the presence of nifedipine/Cyclopiazonic acid/phenylephrine or nifedipine/Cyclopiazonic acid/KCl 60, suggesting a possible inhibition of calcium influx by store operated channels (SOCs), receptor operated channels (ROCs) and/or TRP channels. Interestingly, among the TRP channel blockers used, the effect induced by carvacrol was attenuated by Mg2+ and potentiated by La3+ and Gd3+, suggesting that TRP channels are involved in relaxation induced by carvacrol. Monoterpene also induced hypotension and bradycardia in non-anesthetized normotensive rats and negative inotropic and chronotropic effects. In conclusion, these results suggest that the hypotensive effect of carvacrol is probably due to bradycardia and a peripheral vasodilatation that involves, at least, the inhibition of the Ca2+ influx through Cav and TRP channels.