Renin expression in COX-2-knockout mice on normal or low-salt diets.
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Experiments were performed in mice to investigate whether cyclooxygenase-2 (COX-2) in epithelial cells near the tubulovascular contact point (macula densa and TAL cells) may regulate renin gene expression in juxtaglomerular granular cells. Renin activity, afferent arteriolar granularity, and renin mRNA were determined in wild-type mice and in COX-2-knockout mice on control and low-NaCl diets. Renin activity in microdissected glomeruli assessed as angiotensin I formation in the presence of excess substrate and afferent arteriolar granularity determined by direct visualization and immunostaining were significantly reduced in COX-2 -/- compared with wild-type animals. Similarly, renal cortical mRNA levels were lower in COX-2 -/- than in wild-type mice. Maintaining mice on a low-salt diet for 14 days induced an increase in renin mRNA, afferent arteriolar granularity, and renin activity in wild-type mice. In contrast, renin mRNA and renin granularity did not significantly increase in low-salt-treated COX-2 -/- mice, whereas the increase in juxtaglomerular renin enzyme activity was markedly attenuated, but not fully blocked. In additional experiments we found that COX-2 mRNA was increased in angiotensin type 1A receptor-knockout mice compared with wild-type mice. We conclude that COX-2 in the tubulovascular contact region is a critical determinant of renin synthesis in granular cells under resting conditions and that it participates in the stimulation of renin expression caused by a low-NaCl intake. (+info)
Salt, blood pressure, and human health.
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The positive relation of sodium intake and blood pressure, first recognized a century ago, has been well established in ecological, epidemiological, and experimental human studies. Equally well established is the association of increasing blood pressure and cardiovascular morbidity and mortality. Indeed, the pharmacological capacity to reduce blood pressure has produced one of the great public health accomplishments of the 20th century. These two facts-the positive relation of blood pressure to strokes and heat attacks and the positive association of sodium intake to blood pressure-underlie the hypothesis that a reduction in sodium intake, by virtue of its hypotensive effect, might prevent strokes and heart attacks. Moreover, even if the effect on blood pressure were in the range of a 1- to 2-mm Hg decline in blood pressure for every 75- to 100-mmol difference in sodium intake, the impact of such a change, applied to the whole population, would be enormous. The problem with this appealing possibility is that a reduction in salt consumption of this magnitude has other-and sometimes adverse-health consequences. The question, therefore, is whether the beneficial hypotensive effects of sodium restriction will outweigh its hazards. Unfortunately, few data link sodium intake to health outcomes, and that which is available is inconsistent. Without knowledge of the sum of the multiple effects of a reduced sodium diet, no single universal prescription for sodium intake can be scientifically justified. (+info)
Lack of functional and morphological susceptibility of the greater superficial petrosal nerve to developmental dietary sodium restriction.
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Restriction of dietary sodium during gestation has major effects on taste function and anatomy in the offspring. The chorda tympani nerve of offspring that are maintained on sodium-reduced chow throughout life (NaDep) has reduced neurophysiological responses to sodium and altered morphology of its terminal field in the nucleus of the solitary tract. There are many anatomical and physiological similarities between the chorda tympani nerve that innervates taste buds on the anterior tongue and the greater superficial petrosal nerve (GSP) that innervates taste buds on the palate. To determine if the GSP is similarly susceptible to the effects of dietary sodium restriction, the present study examined neurophysiological responses and the terminal field of the GSP in NaDep and control rats. Neurophysiological responses of the GSP to a variety of sodium and non-sodium stimuli did not differ between NaDep and control rats. Furthermore, the volume and shape of the GSP terminal field in the nucleus of the solitary tract did not differ between the groups. Therefore, despite the high degree of functional and anatomical correspondence between the chorda tympani nerve and the GSP, the GSP does not appear to be susceptible to the effects of lifelong dietary sodium restriction. (+info)
Special diets in hospitals: discrepancy between what is prescribed and what is eaten.
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An assessment has been made in four hospitals of the food eaten by 40 patients on special diets restricted in energy, carbohydrate, fat, protein, or sodium. The diets eaten by most patients were significantly different from those prescribed, partly because of patients' unrestricted access to food they possessed or could buy in the ward, but mainly because of the extra or alternative foods provided by ward staff. Not only may the patients, progress be prevented or hindered by excessive consumption but also the lack of progress may be interpreted as indicating that the dietary treatment has failed rather than that it has not been followed. (+info)
Voltage-dependent Ca2+ channels in resistance arteries from Dahl salt-sensitive rats.
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To determine whether chronic salt-loading would alter voltage-dependent Ca2+ channels in resistance arteries of Dahl salt-sensitive rats, whole-cell voltage-clamp experiments were performed on single cells that were isolated from small mesenteric arteries. Dahl salt-sensitive rats were fed either an 8% NaCl diet (high-NaCl group) or a 0.3% NaCl diet (low-NaCl group) from the age of 6 or 7 weeks. After 4 to 5 weeks, systolic blood pressure was significantly higher in the high-NaCl group than in the low-NaCl group. In the high-NaCl group, the threshold potential for Ca2+ channel current was more negative and the current amplitude that was normalized by cell capacitance was higher at negative command potentials (-40 mV to -20 mV), as compared with the low-NaCl group. When the current was separated into fast transient current and slow sustained (L-type) current, the alteration in the high-NaCl group was attributable to the change in L-type current. The steady-state inactivation curve was not different between the high-NaCl and low-NaCl groups. In conclusion, L-type Ca2+ channels in resistance arteries of Dahl salt-sensitive rats became more available for opening near the resting potential after dietary salt-loading. (+info)
Activation of epithelial Na channels during short-term Na deprivation.
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The role of epithelial Na channels in the response of the kidney to short-term Na deprivation was studied in rats. Animals were fed either a control-Na (3.9 g/kg) or a low-Na ( 3.8 mg/kg) diet for 15 h. Urinary excretion of Na (micromol/min), measured in conscious animals in metabolic cages, was 0.45 +/- 0.07 in controls and 0.04 +/- 0.01 in Na-deprived animals. Glomerular filtration rate, measured as the clearance of creatinine, was unaffected by the change in diet, suggesting that the reduced Na excretion was the result of increased Na reabsorption. K excretion (micromol/min), increased after the 15-h period of Na deprivation from 0.70 +/- 0.10 to 1.86 +/- 0.19. Thus the decrease in urine Na was compensated for, in terms of electrical charge balance, by an increase in urine K. Plasma aldosterone increased from 0.50 +/- 0.08 to 1.22 +/- 0.22 nM. Principal cells from cortical collecting tubules isolated from the animals were studied by using the patch-clamp technique. Whole cell amiloride-sensitive currents were negligible in the control group (5 +/- 4 pA/cell) but substantial in the Na-deprived group (140 +/- 28 pA/cell). The abundance of the epithelial Na channel subunits, alpha, beta, and gamma in the kidney was estimated by using immunoblots. There was no change in the overall abundance of any of the subunits after the 15-h Na deprivation. However, the apparent molecular mass of a fraction of the gamma-subunits decreased as was previously reported for long-term Na deprivation. Calculations of the rate of Na transport mediated by the Na channels indicated that activation of the channels during short-term Na deprivation could account in large part for the increased Na reabsorption under these conditions. (+info)
Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group.
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BACKGROUND: The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. METHODS: A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. RESULTS: Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension. CONCLUSIONS: The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods. (+info)
Cytochrome c mediates apoptosis in hypertensive nephrosclerosis in Dahl/Rapp rats.
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BACKGROUND: Renal damage from hypertension is the second most common cause of end-stage renal failure in the United States. The pathogenesis of this process is incompletely understood. The Dahl/Rapp salt-sensitive (S) rat is a model of low-renin hypertension, but these rats also develop renal lesions that are virtually identical to human hypertensive nephrosclerosis. METHODS: To explore apoptosis as a mechanism of progressive renal injury in S rats, age- and sex-matched S and Sprague-Dawley (SD) rats were placed on either 0.3 or 8.0% NaCl diets, which were continued for 21 days. RESULTS: At day 7, renal histology appeared relatively normal, but by day 21 on the high-salt diet, S rats displayed morphological evidence of severe renal injury that included glomerulosclerosis, arteriolosclerosis, and tubulointerstitial damage. Apoptosis was demonstrated in kidneys of hypertensive S rats by day 7. Cytoplasmic content of cytochrome c was increased in the kidney cortex of hypertensive S rats, and isolated mitochondria showed inappropriate release of cytochrome c sufficient to activate caspase-3 in vitro. Activation of caspase-9 and caspase-3 was observed only in kidney cortex from hypertensive S rats. CONCLUSIONS: Kidneys from hypertensive S rats display apoptosis related to mitochondrial release of cytochrome c and activation of caspase-9 and caspase-3. The findings support a primary role of cytochrome c release and apoptosis in the pathogenesis of hypertensive nephrosclerosis in S rats. (+info)