Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats.

Perinatal taurine excess or deficiency influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed with normal rat chow with 3% ß-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS), or water alone (control, C) from conception to weaning. Their male offspring were fed with normal rat chow and tap water throughout the experiment. At 8-10 weeks of age, blood chemistry, arterial pressure, heart rate, and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine, and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low- (0.3-0.5 Hz) and high-frequency (0.5-4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve, and arterial pressure power spectral densities in the 0.3-4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very-low-frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in adult male rats.

Impaired renal response to portal infusion of hypertonic saline in adriamycin-treated rats.

1. The hepatorenal reflex plays an important role in water and salt homeostasis by matching renal excretion to gastrointestinal absorption. This homeostatic mechanism is impaired in nephrotic rats. The present study tested the hypothesis that, in nephrotic rats, the renal sodium excretion response to hypertonic saline infusion is impaired due to decreased sensitivity of the hepatoportal sodium-sensing mechanism. 2. The present study was performed in control and adriamycin (ADR)-induced nephrotic syndrome rats. After baseline data collection, urinary sodium (U(Na)V) and potassium (U(K)V) excretion responses were tested following continuous infusion of hypertonic NaCl solution (20 µL/min for 30 min) into either the femoral or mesenteric vein. A second series of experiments tested hepatic and renal nerve responses to continuous mesenteric vein infusion of hypertonic NaCl (10 µL/s for 30 s). 3. Compared with control rats, nephrotic rats displayed significantly lower baseline U(Na)V and U(K)V excretion. In control rats, mesenteric compared with femoral vein infusion of hypertonic NaCl produced a more rapid and greater increase in U(Na)V. In contrast, in nephrotic rats, femoral and mesenteric vein infusion caused similar increases in U(Na)V and the maximum increases in U(Na)V to either route of infusion were much lower in nephrotic than control rats. Furthermore, portal hypertonic saline infusion caused greater increases in hepatic nerve activity and greater decreases in renal nerve activity in control compared with nephrotic rats. 4. These data suggest that, in rats, adriamycin treatment decreases hepatoportal sodium-sensing sensitivity, leading to marked impairment of hepatorenal reflex responses, potentially contributing to salt and water retention.

High sugar intake exacerbates cardiac reperfusion injury in perinatal taurine depleted adult rats.

Perinatal taurine depletion and high sugar diets blunted baroreflex function and heightens sympathetic nerve activity in adult rats. Cardiac ischemia/reperfusion also produces these disorders and taurine treatment appears to improve these effects. This study tests the hypothesis that perinatal taurine exposure predisposes recovery from reperfusion injury in rats on either a basal or high sugar diet. Female Sprague-Dawley rats were fed normal rat chow with 3% beta-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Male offspring were fed normal rat chow and water containing 5% glucose (G) or water alone (W) throughout the experiment. At 7-8 weeks of age, all rats were anesthetized and their trachea clamped until cardiac arrest occurred and mean arterial pressure fell below 60 mm Hg. The clamp was immediately released and cardiopulmonary resuscitation was performed with cardiac function returning within 4 min. Twenty-four hours later, arterial pressure, heart rate, and baroreflex function were measured in conscious and one day later in anesthetized conditions. Basic blood chemistry and circulating markers of cardiac injury were also measured. Baroreflex sensitivity was depressed moderately in CG and TDW, and severely in TDG. TSW displayed increased baroreflex and high sugar intake returned it to CW. Sympathetic nerve activity increased and parasympathetic decreased in TDW but not TSW and these effects were exacerbated sharply in TDG and slightly in TSG. Arterial pressure and heart rate increased in all groups but to a lesser degree in TDG. Plasma aspartate aminotransferase increased in all groups except TSW, but the increase was nearly 3X greater in TDG vs. any other group. Creatine kinase-MB increased in all groups except TSG and was far greater in TD than other groups. Troponin-T and brain natriuretic peptide were greatly increased in TDG compared to all other groups. Thus, perinatal taurine depletion increases injury from cardiac ischemia/reperfusion, and in adult rats on a high sugar diet, these effects are greatly exacerbated.

High sugar intake via the renin-angiotensin system blunts the baroreceptor reflex in adult rats that were perinatally depleted of taurine.

Perinatal taurine depletion leads to several physiological impairments in adult life, in part, due to taurine's effects on the renin-angiotensin system, a crucial regulator of growth and differentiation during early life. The present study tests the hypothesis that perinatal taurine depletion predisposes adult female rats to impaired baroreceptor control of arterial pressure by altering the renin-angiotensin system. Female Sprague Dawley (SD) rats were fed normal rat chow and from conception to weaning drank 3% beta-alanine in water (taurine depletion, TD) or water alone (Control, C). Female offspring ate a normal rat chow and drank water with (G) or without (W) 5% glucose throughout the experiment. To test the possible role of the renin-angiotensin system, 50% of the rats received captopril (an angiotensin converting enzyme inhibitor, 400 mg/L) from 7 days before parameter measurements until the end of experiment. At 7-8 weeks of age, arterial pressure, heart rate, baroreflex control of heart rate and renal nerve activity were studied in either conscious, freely moving or anesthetized rats. Perinatal taurine depletion did not alter resting mean arterial pressure or heart rate in the adult female offspring that received either high or normal sugar intake. Captopril treatment slightly decreased mean arterial pressure but not heart rate in all groups. Compared to controls, only the TDG rats displayed blunted baroreflex responses. Captopril treatment normalized baroreflex sensitivity in TDG. The present data indicate that in perinatal taurine depleted female rats, the renin-angiotensin system underlines the ability of high sugar intake to blunt baroreceptor responses.

Adult renal function is modified by perinatal taurine status in conscious male rats.

Perinatal taurine exposure influences renal function in adult female offspring. This study tests the hypothesis that prenatal rather than postnatal taurine exposure alters renal function in adult conscious male rats. Female Sprague Dawley rats were fed normal rat chow and tap water alone (Control), tap water containing 3% beta-alanine (taurine depletion, TD) or tap water containing 3% taurine (taurine supplementation, TS) either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). After weaning, male offspring were fed with the normal rat chow and tap water ad libitum. At 7-8 weeks of age, renal function was studied in conscious, restrained rats. Mean arterial pressures were slightly higher in rats receiving taurine supplementation during either the fetal or lactation periods (compared to Control and TD groups), but heart rates were not significantly different among groups. Effective renal blood flows were lower in TDF, TDL, and TSF rats (TDF 4.6+/-0.8 ml/min/g kidney weight (KW), TDL 3.0+/-0.9 ml/min/g KW, and TSF 2.8+/-0.7 ml/min/g KW) than in TSL (7.7+/-0.9 ml/min/g KW) or Control rats (7.3+/-1.6 ml/min/g KW). These differences were correlated with significant increases in renal vascular resistance in TDF, TDL, and TSF groups compared to TSL and Control rats. In contrast, glomerular filtration rates were not significantly different among groups. Although basal water and sodium excretion were slightly lower in TDL and TSF rats compared to other groups, their diuretic and natriuretic responses to an acute saline load were not different from Control. The present data indicate that in adult male rats, both perinatal supplementation and depletion of taurine can alter renal hemodynamics, and these effects are differentially time-dependent.

Perinatal taurine exposure alters renal potassium excretion mechanisms in adult conscious rats.

Perinatal taurine exposure has long-term effects on the arterial pressure and renal function. This study tests its influence on renal potassium excretion in young adult, conscious rats. Female Sprague-Dawley rats were fed normal rat chow and given water alone (C), 3% beta-alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). In Experiment 1, male offspring were fed normal rat chow and tap water, while in Experiment 2, beta-alanine and taurine were treated from conception until weaning and then female pups were fed normal rat chow and 5% glucose in drinking water (CG, TDG or TSG) or water alone (CW, TDW or TSW). At 7-8 weeks of age, renal potassium excretion was measured at rest and after an acute saline load (5% of body weight) in conscious, restrained rats. Although all male groups displayed similar renal potassium excretion, TSF rats slightly increased fractional potassium excretion at rest but not in response to saline load, whereas TDF did the opposite. Plasma potassium concentration was only slightly altered by the diet manipulations. In female offspring, none of the perinatal treatments significantly altered renal potassium excretion at rest or after saline load. High sugar intake slightly decreased potassium excretion at rest in TDG and TSG, but only the TDG group displayed a decreased response to saline load. The present data indicates that perinatal taurine exposure only mildly influences renal potassium excretion in adult male and female rats.

Perinatal taurine depletion increases susceptibility to adult sugar-induced hypertension in rats.

This study tests the hypothesis that perinatal taurine depletion produces autonomic nervous system dysregulation and increases arterial pressure in young male rats maintained on a high sugar diet. Sprague-Dawley dams were either taurine depleted (beta-alanine 3% in water) or left untreated from conception to weaning. Their male offspring were fed normal rat chow with or without 5% glucose. At 7-8 weeks of age, the male offspring were either tested in a conscious, unrestrained state or after anesthetia. Body weight was slightly lower in the taurine-depleted rats although their heart or kidneys to body weight ratios were similar. Plasma potassium, blood urea nitrogen, plasma creatinine, hematocrit, fasting blood glucose concentrations and glucose tolerance were all similar. In the taurine-depleted, high glucose group, mean arterial pressure and sympathetic nervous system activity were increased while baroreflex function was impaired. These findings suggest that in this model perinatal taurine depletion causes autonomic nervous system dysfunction that may contribute to dietary high sugar-induced hypertension.

Sex dependent effects of perinatal taurine exposure on the arterial pressure control in adult offspring.

The present study tests the sex-dependent effect of perinatal taurine exposure on arterial pressure control in adults. Female Sprague-Dawley rats were fed normal rat chow with 3% beta-alanine (taurine depletion,TD), 3% taurine (taurine supplementation,TS) or water alone (C) from conception to weaning. Their male and female offspring were then fed normal rat chow and tap water with 5% glucose (C with glucose, CG; TD with glucose, TDG; TS with glucose, TSG) or water alone (CW, TDW or TSW). At 7-8 weeks of age, they were studied in a conscious condition. Body weights were lower in male and female TDG and male TDW rats. Kidney to body weights increased in female TSW but not TSG. Plasma sodium and potassium were not significantly different among males. Among females, plasma sodium levels were lower in all glucose treated groups while plasma potassium levels were lower only in TDG. Hematocrit, fasting blood glucose, and glucose tolerance were not significantly different between the sexes. Mean arterial pressure increased in male TDG, TSW, and TSG while in the females, mean arterial pressure increased in TabstractDW, TDG, and TSG. Heart rates were not significantly different between the sexes. The present data indicate that perinatal taurine exposure alters arterial pressure control of adult rats and this effect is gender specific.

Perinatal taurine alters arterial pressure control and renal function in adult offspring.

The present study investigates the effect of perinatal taurine exposure on renal function in adult, female rats on a high sugar diet. Perinatal taurine depleted (TD), supplemented (TS) or untreated control (C) female offspring were fed normal rat chow and tap water (CW,TDW or TSW) or tap water with 5% glucose (CG, TDG or TSG) after weaning. At 7-8 weeks of age, renal function was studied in the conscious, restrained rats. Mean arterial pressure was significantly higher in TDW, TDG, and TSG rats. Plasma sodium concentration was significantly lower in all glucose treated animals, but the greatest decrease was in TDW rats. Basal renal blood flow was lowest in TSW and TSG, and the responses to a saline load were also lowest in those two groups. These changes were consistent with increased renal vascular resistance. The basal glomerular filtration rate was lowest in TSW, but the responses to a saline load were similar in all of the groups. Water excretion was lower in TSG and TSW, consistent with increased renal tubular water reabsorption. These data suggest that perinatal taurine exposure alters normal renal function and renal responses to dietary sugar in adult female offspring.

Abnormal autonomic nervous system function in rural Thai men: A potential contributor to their high risk of sudden unexplained nocturnal death syndrome.

BACKGROUND: Rural compared to urban Thai populations have a higher incidence of sudden unexplained nocturnal death syndrome (SUNDS). This study tests the hypothesis that compared to young urban Thai men, the young rural northeast Thai men display autonomic system dysfunction that may contribute to their relatively high risk to develop SUNDS. METHODS: Forty-seven healthy second and third year students from Khon Kaen University (20-22years old) were divided into central, urban northeastern, and rural northeastern groups, based on the locality in which they had grown up and in which their parents had lived prior to their birth. RESULTS: Body weight, body height, serum sodium, serum potassium, fasting blood sugar, glucose tolerance, resting mean arterial pressure, resting heart rate, ulnar nerve conduction velocity, and sympathetic and parasympathetic nervous system activity were not significantly different among the three groups. In contrast, compared to urban northeasterners and central Thais, rural northeasterners displayed low sympathetic and high parasympathetic responses to cold stress and oral saline load; however, baroreflex sensitivity and the autonomic nervous system responses to upright tilt were not significantly different among the three groups. In addition, respiratory rates at rest and in response to upright tilt, cold stress, and oral saline load were not significantly different among the three groups. CONCLUSIONS: These data indicate that compared to central or urban, individuals from rural origin display decreased sympathetic and increased parasympathetic responses to stresses. These altered responses could predispose the individuals to inappropriate autonomic control during the stresses, including those resulting in SUNDS.

Excess dietary glucose alters renal function before increasing arterial pressure and inducing insulin resistance.

BACKGROUND: Diets high in carbohydrates are associated with hypertension, activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal dysfunction. This study tests the hypothesis that the initial effect of a long-term high carbohydrate diet is a renin-angiotensin system dependant impairment of renal function. METHODS: Three-week-old male Sprague-Dawley rats drank water containing 5% glucose or water alone. Four weeks later, arterial pressure was continuously recorded in conscious restrained rats. Urine and blood samples were collected by catheter before, during, and after intravenous saline infusion, and fasting glucose tolerance tests were performed to estimate insulin resistance. To assess the possible role of the renin-angiotensin system, a group of glucose-fed rats was treated with oral captopril for 2 days before the renal function study. RESULTS: Despite slightly and significantly lowered body weight, the treatments did not significantly alter heart and kidney weights, arterial pressure, or heart rate. Non-fasting blood sugar levels were slightly higher in the two groups of glucose-fed rats compared with the control rats (P < .05), but fasting blood sugar concentration and glucose tolerance were not significantly different among groups. The glucose-fed rats displayed significantly impaired renal diuresis and natriuresis as well as significantly elevated glomerular filtration rate and filtration fraction, but administration of captopril corrected these impairments. Effective renal blood flow and renal vascular resistance were not significantly different among groups. CONCLUSIONS: These results indicate that diets high in carbohydrates impair renal function before they increase arterial pressure, and that this effect is dependent on an intact renin-angiotensin system.

Changes in erythrocyte contents of potassium, sodium and magnesium and Na, K-pump activity after the administration of potassium and magnesium salts.

Low potassium and magnesium status and decreased Na, K-pump activity is an endemic condition among rural Northeast Thais. The authors examined the effect of supplementing potassium and magnesium on erythrocyte potassium, sodium and magnesium content and on Na, K-pump activity. Rural Northeast Thai renal stone patients (62) were recruited, divided into four groups and supplemented for one month with potassium chloride (Group1, n = 16), potassium-sodium citrate (Group2, n = 15), chelated magnesium (Group 3, n =16) and potassium-magnesium citrate (Group 4, n =15) in order to achieve 40 mmol potassium, 10 mmol magnesium and 60 mmol citrate daily. After supplementation with potassium (Groups 1, 2 and 4), plasma potassium and Na, K-pump activity rose significantly in Groups 1, 2 and 4, but erythrocyte potassium rose only in Groups 2 and 4. When supplementing elemental magnesium (Groups 3 and 4), the chelated magnesium caused a significant increase in plasma potassium, erythrocyte potassium, sodium and magnesium without a significant increase in Na, K-pump activity. By contrast, potassium-magnesium citrate caused a significant increase in erythrocyte potassium and magnesium and Na, K-pump activity, but depressed erythrocyte sodium. These results suggest the forms of potassium and /or magnesium salts being supplemented should be considered because they affect erythrocyte potassium, sodium and magnesium content and Na, K-pump activity differently.