The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.

This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate. Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention. At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria. Randomization either to weight-loss group (mean loss of 4.5 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group. Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%). These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy.

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RNA-binding proteins act at various stages of gene expression to regulate and fine-tune patterns of mRNA accumulation. One protein in this class is Drosophila Su(s), a nuclear protein that has been previously shown to inhibit the accumulation of mutant transcripts by an unknown mechanism. Here, we have identified several additional RNAs that are downregulated by Su(s). These Su(s) targets include cryptic wild-type transcripts from the developmentally regulated Sgs4 and ng1 genes, noncoding RNAs derived from tandemly repeated ␣␤/␣␥ elements within an Hsp70 locus, and aberrant transcripts induced by Hsp70 promoter transgenes inserted at ectopic sites. We used the ␣␤ RNAs to investigate the mechanism of Su(s) function and obtained evidence that these transcripts are degraded by the nuclear exosome and that Su(s) promotes this process. Furthermore, we showed that the RNA binding domains of Su(s) are important for this effect and mapped the sequences involved to a 267-nucleotide region of an ␣␤ element. Taken together, these results suggest that Su(s) binds to certain nascent transcripts and stimulates their degradation by the nuclear exosome.

SUMMARY Fractional excretion of lithium, as a marker for proximal sodium reabsorption, was determined in normotensive Dahl S rats (susceptible to NaCI hypertension) and Dahl R rats (resistant to NaCI hypertension) before and following an acute sodium load. Baseline mean arterial pressures, inulin clearances, sodium excretion rates, and fractional lithium clearances were not different between the R and S rats. Following the salt loading and despite similar mean arterial pressures and degree of volume expansion, the glomerular filtration rate, urinary flow rates, and absolute sodium excretion rates were greater in R than S rats. The fractional excretion of lithium was also greater in R than S rats. These data demonstrate that, at equal mean arterial pressures, Dahl S rats have a reduced capacity for sodium excretion, and that this defect is present prior to the development of hypertension. Furthermore, the observation that these animals also have a lower fractional lithium excretion during volume expansion suggests that salt loading reduces proximal tubule reabsorption to a lesser extent in Dahl S than R rats. These data suggest that the subnormal sodium and water excretion observed after sodium loading in S rats may be partially due to an abnormality in proximal tubule sodium handling. (Hypertension 6: 420-^24, 1984) KEY WORDS * fractional lithium excretion renal sodium handling Dahl rats • volume expansion O NE hypothesis to explain essential hypertension suggests that hypertensive individuals are more sensitive to the effects of dietary sodium than nonhypertensive individuals. Although the relationship of dietary sodium to human essential hypertension has been difficult to define precisely, increased sensitivity to dietary sodium ingestion is the mechanism for development of hypertension in several animal models such as the Dahl rat.1 These animals exist as two strains: a salt-sensitive (S) strain, which develops hyertension when ingesting a high sodium diet, and a salt-resistant (R) strain which is insensitive to salt intake. The etiology for the salt sensitivity in the S rats is uncertain. However, finding that salt sensitivity can be transferred from S to R animals by transplan- tation of an S strain kidney suggests that the kidney plays a major role in this phenomena. 2 A partial explanation for this phenomena has been provided by Tobian et al. 3 who demonstrated that for any given perfusion pressure, isolated perfused kidneys from S animals excrete less sodium than do kidneys from R animals. While several other groups of investigators have confirmed a reduced pressure natriuresis in isolated perfused kidneys from S rats, whether reduced sodium excretion also occurs in S rats in vivo has yet to be determined. Furthermore, there is some debate as to whether the reduction in sodium excretion observed in isolated perfused kidneys from S rats is a cause or an effect of the elevation in arterial pressure.3 " 5 Finally, the mechanisms responsible for the reduced pressure natriuresis observed in S rat kidneys...

SUMMARY Results of blood pressure (BP) and urinary electrolyte excretion studies are reported among several groups of adolescent and young adult females, both black and white, who were Initially examined in high school and restudied at home 3-4 years later. Pooling of the data from the sereral cross-cectional studies (n = 662) rerealed a weak but statistically significant positive correlation between systolic blood pressure (SBP) and the urinary sodium (Na) excretion rate. Three of four correlations between SBP and potassium (K) were of an inverse nature. Although not statistically significant in their own right, when coupled with the Na/K excretion ratio, which was significantly associated with SBP, a moderating role for K b suggested. The urinary Na, K, and creatinine (Cr) excretion rates were highly intercorrelated and were correlated with weight. As measured by R 1 in a stepwise regression analysis, weight contributed approximately 3% to the BP variance, and the urinary electrolytes accounted for approximately 2% of the SBP variance. Statistically significant partial correlation coefficients between SBP and Na, and Na/K, remained after adjusting for body weight. T HERE is much experimental evidence to suggest that the ingestion of high levels of sodium (Na) may play a role in the genesis of high blood pressure (BP) among several species of laboratory animals. The evidence for such a relationship among human populations, however, is equivocal. Human studies that have tried to show a direct association between urinary electrolyte excretion rates and BP utilizing cross-sectional data have been largely unsuccessful.

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In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P less than 0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P less than 0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs.