Sanya Roysommuti

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.

Perinatal taurine exposure affects adult arterial pressure control

Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine’s contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin–angiotensin system, glucose–insulin interaction and changes to heart, blood vessels and kidney function.

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.

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.

Perinatal taurine exposure affects adult oxidative stress

Perinatal exposure to taurine (a β-amino acid) can alter adult physiological functions, including arterial pressure, hormonal and renal functions. Whereas perinatal taurine supplementation appears to have only minor effects on adult physiology, perinatal taurine depletion is associated with multiple adverse health effects, especially in animals postnatally exposed to other insults. New studies indicate that the mechanism for many of the physiological effects of taurine is related to the antioxidant activity of taurine. Thus the perinatal taurine depletion leads to oxidative stress in adult animals. It is likely that perinatal taurine depletion increases oxidative stress throughout life and that the early life taurine depletion leads to perinatal, epigenetic programming that impacts adult physiological function.

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.

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.

Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications.

Taurine (2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions.

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% β-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.