HNa Diet Research Articles

Effects of Dietary Supplementation of Humic Acid Sodium and Zinc Oxide on Growth Performance, Immune Status and Antioxidant Capacity of Weaned Piglets.

Simple SummaryWeaning of piglets can destroy the piglet’s intestinal health and immune function, leading to diarrhea and a reduction in growth rate eventually. Considering drug resistance and residues, new alternatives, such as sodium humate (HNa), have attracted considerable research interest over recent decades. Our study was designed to explore the effect of HNa on the growth performance, diarrhea rate, antioxidative, inflammation, and immunity of weaned piglets and the possibility of HNa replacing antibiotics and zinc oxide. The obtained results indicate that HNa reduces stress, protects the intestinal barrier, and improves the performance of weaned piglets.At present, the widespread use of high-dose zinc oxide and antibiotics to prevent post-weaning diarrhea (PWD) in piglets has caused serious environmental problems. To solve this problem, we studied the effect of HNa as a substitute for zinc oxide (ZnO) and antibiotics on the growth performance, immune status, and antioxidant capacity of piglets. Seventy-two weaned piglets (body weight = 7.42 ± 0.85 kg, 26-d-old) were distributed in a randomized 2 × 3 factorial design (two sexes and three treatments) with six replicates of four piglets each. The three treatments were the control diet (basic diet), HNa diet (basic diet + 2000 mg/kg sodium humate), and ZoA group (basic diet + 1600 mg/kg zinc oxide + 1000 mg/kg oxytetracycline calcium). ANOVA and Chi-square tests were applied to compare the means (p < 0.05) between treatments. The results showed that body weight at 16 and 30 d and the average daily gain of piglets fed with HNa or ZoA were significantly higher (p < 0.05) than the control group. Supplementing HNa or ZoA significantly increased (p < 0.05) the level of immunoglobulin M and G, and reduced (p < 0.05) the concentration of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukins IL-6 and IL-1β, myeloperoxidase (MPO), and diamine oxidase (DAO). Furthermore, dietary HNa or ZnO significantly reduced (p < 0.05) the level of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) compared with the control group. ZoA treatment showed an upward trend of IgA level and a downward trend of the concentration of lipopolysaccharide (LPS) and catalase (CAT). Overall, the study demonstrated that the addition of HNa in the diet partially replaced antibiotics and ZnO to improve the growth performance, immune function, and antioxidant capacity of weaned piglets, and maintained a good preventive effect on piglet diarrhea.

Inclusion of Dairy Cheese In An 8‐day Controlled Dietary Intervention Prevents Sodium‐Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy Older Adults

Excess dietary sodium is associated with impaired vascular function and increased cardiovascular mortality. In controlled feeding studies, the inclusion of 3 daily servings of any dairy product improves blood pressure and measures of vascular health. Few studies have examined the inclusion of individual dairy products that contain both the beneficial bioactive dairy proteins and sodium. We recently demonstrated that single‐meal cheese consumption ameliorates acute sodium‐induced impairments in nitric oxide‐dependent vasodilation. However, controlled feeding studies examining the vasoprotective role of dairy cheese on sodium‐induced microvascular dysfunction are lacking. We hypothesized that (1) endothelium‐dependent vasodilation would be impaired by a high‐sodium diet compared to a low sodium diet, and (2) that a high‐cheese diet would preserve endothelium‐dependent vasodilation that is otherwise impaired by a high‐sodium diet. In a randomized, crossover study design, seven healthy older adults (63 ± 3 years; salt‐resistant: &lt;10 mmHg increase in mean arterial pressure, 24 hour monitoring) with normal to elevated blood pressure completed 4 separate 8‐day controlled dietary interventions: 1) low‐sodium (LNa: 1500 mg sodium) diet devoid of dairy products, 2) low‐sodium high‐cheese diet (LNaC: 1500 mg sodium, 6 oz/d cheese), 3) high‐sodium (HNa: 5500 mg sodium) diet devoid of dairy products, and 4) high‐sodium high‐cheese diet (HNaC: 5500 mg sodium, 6 oz/d cheese). At the end of each dietary intervention, subjects participated in an intradermal microdialysis protocol in which one microdialysis fiber was inserted into the forearm skin for measurement of red cell flux (laser Doppler flowmetry) during local infusion of the endothelium‐dependent agonist acetylcholine (Ach; 10−12 to 10−1 M). Data were expressed as a percentage of maximum cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside, 43°C). Ach‐induced vasodilation was significantly attenuated during the HNa diet compared to the LNa diet (LNa: −5.06±0.20 M vs HNa: −3.22±0.63 M logEC50: p &lt; 0.05). Conversely, Ach‐induced dilation during either the LNaC or HNaC diet was not different from the LNa diet (p &gt; 0.05). These results demonstrate that increased dietary sodium intake impairs endothelium‐dependent dilation whereas the inclusion of cheese prevents sodium‐induced endothelial dysfunction in salt‐insensitive older adults.Support or Funding InformationSupported by National Dairy CouncilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study.

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats (n = 8-10 per group) were either on a normal (NNa; 0.4% NaCl)- or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06-0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03-0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups (P < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min(-1)·g kidney wt(-1), P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (-0.02 ± 0.50 dB, P < 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.

Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 +/- 1,470 vs. 900 +/- 390%.s. The norepinephrine (NE) concentration required to increase PGE(2) and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE(2) release from 67 +/- 6 to 150 +/- 13 pg/min and substance P release from 6.7 +/- 0.8 to 12.3 +/- 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE(2) release from 64 +/- 5 to 129 +/- 22 pg/min and substance P release from 4.5 +/- 0.4 to 6.6 +/- 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE(2) and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE(2) release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.

EFFECT OF PERIPHERAL SYMPATHETIC NERVE DYSFUNCTION ON SALT SENSITIVITY OF ARTERIAL PRESSURE

1. Dysregulation of peripheral sympathetic pathways contributes to some forms of salt-dependent hypertension. However, at the present time it is not known whether salt-induced activation of sympathetic nerves or loss of normal sympathoinhibitory responses to salt-induced volume expansion contributes to neurogenic salt-dependent hypertension. The present study was performed to the test the hypothesis that loss of peripheral sympathetic nerve function results in salt-dependent hypertension. 2. The effect of three pharmacological interventions of sympathetic nerve function on the long-term salt-sensitivity of mean arterial pressure (MAP) were measured: (i) blockade of ganglionic transmission with hexamethonium (HEX; n = 5); (ii) destruction of sympathetic nerve terminals with guanethidine (GUAN; n = 7); and (iii) alpha-adrenoceptor blockade with two specific antagonists, namely prazosin (PRAZ; n = 7) and terazosin (TERAZ; n = 8). 3. Mean arterial pressure and heart rate were measured 24 h/day by radiotelemetry in conscious rats during 5 days of normal and 7 days of high (HNa) dietary sodium intake. Despite marked increases in both sodium and water intake during 7 days of the HNa diet, no statistically significant changes in MAP were observed in HEX, GUAN, PRAZ or TERAZ groups. 4. We conclude that loss of peripheral sympathetic neural pathways alone does not cause salt-dependent hypertension in the rat.

Interaction between endothelin and angiotensin in the activation of renal sensory nerves

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) and urinary sodium excretion. Low sodium (LNA) diet impairs and high Na diet (HNA) enhances the activation of renal sensory nerves. Renal pelvic administration of losartan or the endothelin A receptor (ETA-R) antagonist BQ123 enhances the activation of renal sensory nerves in LNA diet rats. We now examined if angiotensin (ANG) II suppresses ARNA via interaction with ET. ANG II is present in renal pelvis and its levels are higher in LNA than in HNA diet rats. ET-1 is also present in renal pelvis, its levels being similar in LNA and HNA diet, 13∀2 and 13∀2 pg/mg protein. The ET-1 levels in renal pelvis were lower than in papilla but higher than in cortex; 191∀33 and 1.3∀0.1 pg/mg protein. In LNA diet rats, increasing renal pelvic pressure 7.5 mmHg in the presence of renal pelvic perfusion with vehicle, losartan and losartan+BQ123 increased ARNA 7∀2, 14∀2 and 16∀3%. Thus losartan and losartan+BQ123 resulted in similar enhancements of the ARNA response (P<0.01 vs vehicle). Similar results were produced when renal pelvis was perfused with BQ123 before BQ123+losartan. In isolated renal pelvises from LNA diet rats, PGE2 failed to increase substance P (SP) release. Adding losartan or losartan+BQ123 to the incubation bath enhanced the PGE2-mediated SP release to a similar extent, from 7∀1 to 15∀2 and from 9∀1 to 16∀1 pg/min, both P<0.01. Similar results were produced by incubating pelvises in BQ123 or BQ123+losartan. In isolated pelvises from HNA diet rats, PGE2 increased SP, from 5∀2 to 13∀2 pg/min (P<0.01). Adding ANG II to the bath abolished the PGE2-mediated SP release. However, incubating the pelvises with ANG II+BQ123 restored the PGE2-mediated SP release, from 6∀1 to 13∀1 pg/min (P<0.01). Conclusion, ET-1 by activating ETA-R contributes to ANG II-mediated suppression of the activation of renal sensory nerves.

Regulation of the genes for 11beta-hydroxysteroid dehydrogenase type 1 and type 2 in the kidney of the Dahl rat.

An isoenzyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), 11beta-HSD-2 confers aldosterone specificity on the mineralocorticoid receptor (MR) and is found collocated in renal cortical collecting duct cells with the MR. To investigate whether the salt sensitivity of the Dahl salt-sensitive (S) rat is due to 11beta-HSD deficiency, we measured 11beta-HSD-1 and 11beta-HSD-2 mRNA levels in the kidneys of Dahl-S and Dahl salt-resistant (R) rats. In addition, we studied the effects of gender, age and dietary sodium on expression of mRNA for the two isoforms. S and R rats were placed on low- or high-sodium (HNa) diets and sacrificed after 33 and 115 days. Rat kidney RNA was isolated and 11beta-HSD-1 and 11beta-HSD-2 mRNA levels were measured on Northern filter hybridization using isoform-specific probes. No strain differences were observed in the mRNA expression of the two isoforms of 11beta-HSD under any of the experimental conditions. No gender or age differences were observed in 11beta-HSD-2 mRNA but HNa diet almost doubled 11beta-HSD-2 mRNA (P<0.0009). 11beta-HSD-1 mRNA levels were consistently higher, more than double, in male rats versus females rats (P<0.0001), and in the 115-day-old rats versus the 33-day-old rats (P<0.0001). Dietary sodium intake did not affect 11beta-HSD-1 mRNA levels. There is no difference in the expression of the two isoforms of 11beta-HSD in the kidneys of the S and R rats, which might explain the salt sensitivity and higher blood pressure of the S rat. Renal 11beta-HSD-1 mRNA levels are higher in male than in female rats, and in the older rats of both strains. In the kidney, the 11beta-HSD-2 gene is regulated by sodium status but is not affected by gender or age.

Patterns of neuronal activation during development of sodium sensitive hypertension in SHR.

The effects of regular (RNa) or high (HNa) sodium diet for 3, 7, and 14 days on Fra-like immunoreactivity (Fra-LI) in the brains of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were examined using an antibody that recognizes all known members of the Fos family (Fos, Fos-B, Fra-1, and Fra-2). Two weeks of HNa significantly exacerbated hypertension in SHR but had no effects in WKY. On RNa, compared with WKY, SHR showed higher Fra-LI in the median preoptic nucleus, supraoptic nucleus, both parts of the paraventricular nucleus, nucleus of the solitary tract, and central gray. Fra-LI in the subfornical organ did not differ between the two strains. On RNa, Fra-LI in the anterior hypothalamic area could be detected only in WKY. In osmoregulatory areas, HNa diet increased Fra-LI in both SHR and WKY to comparable extents, but in the median preoptic nucleus, Fra-LI was increased to a greater extent in SHR. HNa produced smaller increases in the subfornical organ of SHR compared with WKY. In both the parvocellular and magnocellular paraventricular nuclei, increases in Fra-LI by HNa were more pronounced in SHR than in WKY. In the anterior hypothalamic area, Fra-LI could no longer be detected in WKY on HNa, whereas it appeared in SHR. HNa increased Fra-LI in the NTS and central gray to similar levels in WKY and SHR. These results indicate that WKY and SHR differ in the pattern of neuronal activation accompanying maturation on RNa. HNa activates neurons in a number of brain areas, and the pattern of these changes also differs between WKY and SHR.