Changes In Potassium Excretion Research Articles

Abstract 13972: Intermittent Occlusion of the Superior Vena Cava Improves Urine Sodium Excretion in Patients With Acutely Decompensated Heart Failure

BACKGROUND: Urine sodium excretion identifies risk for short and long-term adverse events in acutely decompensated heart failure (ADHF). The VENUS HF Early Feasibility Study is testing whether intermittent occlusion of the superior vena cava (SVC) with the preCARDIA system, a catheter mounted balloon and pump console, improves decongestion in ADHF. We hypothesized that preCARDIA therapy increases natriuresis in ADHF. Methods: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 32 patients with ADHF were assigned to preCARDIA therapy for 24 hours. Urine output and urine electrolytes were measured from a spot urine sample before, immediately after, and for 24 hours after preCARDIA treatment in 13 patients. Results: 32 patients were enrolled and received the preCARDIA system. Thirteen patients had complete urine electrolytes available for analysis. Compared to pre-treatment values, total daily urine output increased (1.9±0.8 vs. 4.2±1.5 L/day, p<0.001) and net fluid balance improved (-1.2±0.8 vs. -2.6±1.4 L/day, p=0.01) with treatment. Compared to pre-treatment, urine sodium (U-Na: 64±26 vs 97±24 mEq/L, p=0.0008) and U-Na/urine creatinine (U-Na/U-Cr: 1.7±1.3 vs 5.3±3.9 mmol/mg p=0.024) increased with treatment (Figure). Improved daily urine output and net fluid balance persisted 24 hours after treatment (1.9±0.8 vs 4.4±1.5 L p=0.0001; -1.2±0.8 vs -3.2±1.5 L/24h p=0.0003, respectively). Both U-Na and U-Na/U-Cr remained increased 24 hours after device removal (90 mEq/L, p=0.01; 3.93±2.8 p=0.026). Treatment increased fractional excretion of U-Na (2.08±1.87% vs. 4.22±2.72% p=0.05). No change in potassium excretion was observed. Conclusions: We report for the first time that intermittent SVC occlusion using the preCARDIA system to reduce congestion may increase urinary sodium excretion in ADHF. Future studies will further test the clinical utility of the preCARDIA system.

Association of a Province-Wide Intervention With Salt Intake and Hypertension in Shandong Province, China, 2011-2016

High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide.

Potassium supplementation and heart rate: A meta-analysis of randomized controlled trials

Background and aimsIncreasing the intake of potassium has been shown to lower blood pressure, but whether it also affects heart rate (HR) is largely unknown. We therefore assessed the effect of potassium supplementation on HR in a meta-analysis of randomized controlled trials. Methods and resultsWe searched PubMed (1966–October 2014) for randomized, placebo-controlled trials in healthy adults with a minimum duration of two weeks in which the effect of increased potassium intake on HR was assessed. In addition, reference lists from meta-analysis papers on potassium and blood pressure were hand-searched for publications. Two investigators independently extracted the data. We performed random effects meta-analyses, subgroup and meta-regression analyses for characteristics of the study (e.g. design, intervention duration, potassium dose and salt type, change in potassium excretion, sodium excretion during intervention) and study population (e.g. gender, age, hypertensive status, pre-study HR, pre-study potassium excretion). A total of 22 trials (1086 subjects), with a median potassium dose of 2.5 g/day (range: 0.9–4.7 g/day), and median intervention duration of 4 weeks (range: 2–24 weeks) were included. The meta-analysis showed no overall effect of increased potassium intake on HR (0.19 bpm, 95% CI: −0.44, 0.82). Stratified analyses yielded no significant effects of potassium intake on HR in subgroups, and there was no evidence for a dose–response relationship in meta-regression analyses. ConclusionA chronic increase in potassium intake with supplemental doses of 2–3 g/day is unlikely to affect HR in apparently healthy adults.

The Effect of Amiloride during Infusion of Oxytocin in Male Sprague-Dawley Rats: A Study of a Possible Intrarenal Target Site for Oxytocin

A possible natriuretic mechanism of action of oxytocin was investigated in male Sprague-Dawley rats. The effects of an intravenous bolus injection of amiloride on urine volume, potassium and sodium excretion, and osmolality were measured with and without an intravenous infusion of oxytocin in saline. Control values were obtained during the infusion of saline. Amiloride administered during an oxytocin infusion increased sodium excretion from 0.1 ± 0.0 to 16.6 ± 2.1 μmol/min. In animals treated with amiloride only, the sodium excretion was 4.5 ± 0.8 μmol/min. The administration of oxytocin only resulted in a sodium excretion of 1.2 ± 0.3 μmol/min. After the administration of oxytocin, amiloride increased urinary flow from 4.3 ± 0.6 μl/min to 48.8 ± 6.1 μl/min. In animals treated with amiloride only, the flow after the bolus dose was 17.7 ± 1.8 μl/min. The administration of oxytocin only resulted in a flow of 8.5 ± 1.6 μl/min. The amiloride-caused change in potassium excretion was not inhibited by oxytocin. In summary, the effects of amiloride were not inhibited by the actions of oxytocin. Amiloride administrated after reaching a near steady-state effect of oxytocin was found to give rise to an effect far greater than that after the administration of oxytocin or amiloride alone. It is concluded that the intrarenal natriuretic mechanisms of oxytocin do not emanate from the amiloride-sensitive sodium channels.

Effects of Multiple Oral Doses of an A1Adenosine Antagonist, BG9928, in Patients With Heart Failure: Results of a Placebo-Controlled, Dose-Escalation Study

This study sought to assess the pharmacokinetics and clinical effects of oral BG9928 in heart failure (HF) patients. Declining renal function during HF treatment is associated with poor outcomes. BG9928, a selective inhibitor of the A1adenosine receptor, is proposed to cause natriuresis without causing a decline in renal function. A randomized, double-blind, placebo-controlled study was conducted in patients with HF and systolic dysfunction who were receiving standard therapy. Patients were randomized to receive BG9928 (3, 15, 75, or 225 mg) or placebo orally for 10 days. The primary end point was change in sodium excretion. Changes in potassium excretion, creatinine clearance, and body weight also were evaluated. A total of 50 patients were studied. BG9928 increased sodium excretion compared with placebo, and natriuresis was maintained over 10 days with little kaliuresis. A linear trend in dose response was observed on day 1 (p = 0.04) but not on days 6 or 10. Adjusted creatinine clearance was unchanged over the 10 days. Patients who received 15, 75, or 225 mg of BG9928 had a reduction in body weight compared with placebo (−0.6, −0.7, −0.5, vs. +0.3 kg, respectively) at the end of study. BG9928 was well tolerated. The pharmacokinetic profile of BG9928 was consistent with once-daily dosing. Oral BG9928 over the dose range of 3 to 225 mg/day produced significant increases in sodium excretion in patients with stable HF without causing kaliuresis or reducing renal function.

Potassium Excretion in Healthy Japanese Women Was Increased by a Dietary Intervention Utilizing Home-Parcel Delivery of Okinawan Vegetables

Potassium, which is abundant in vegetables, is inversely related to blood pressure. Although the situation has changed somewhat in recent years, the Okinawan diet has generally included a large amount of vegetables, and until recently Okinawans had the lowest rates of mortality due to stroke and coronary heart disease in Japan. Based on the hypothesis that these low mortality rates are partly attributable to increased potassium intake resulting from the high vegetable consumption, this study examined whether increasing the consumption of typical yellow-green Okinawan vegetables increases potassium intake. The purpose of this investigation was to determine whether increased consumption of these vegetables should be one of the dietary modifications recommended in public health promotion programs for Okinawans. The study employed 56 healthy, normotensive, free-living Japanese women aged 18-38 years living in Okinawa. They were randomized to a dietary intervention group (n=27) or a control group (n=29). Members of the dietary intervention group received an average weight of 371.4 g/day of a combination of the following vegetables twice weekly through an express home parcel deliver service for a period of 14 days: Goya (Momordica charantia), green papaya (Carica papaya), Handama (Gynura bicolor), Karashina (Brassica juncea), Njana (Crepidiastrum lanceolatium), Fuchiba (Artemisia vulgaris) and Fudanso (Beta vulgaris); and they consumed an average of 144.9 g/day, resulting in a 20.5% increase in their urinary potassium excretion over the baseline (p=0.045). The members of the control group were asked to avoid these vegetables, and the change in potassium excretion in this group was not significant (p=0.595). Urinary sodium and magnesium excretions, systolic and diastolic blood pressures, folic acid, triglycerides and serum high density lipoprotein cholesterol, low density lipoprotein cholesterol and total cholesterols changed non-significantly in both groups. Also, post-intervention urinary potassium excretion correlated positively with vegetable consumption in both the dietary intervention (p<0.0001) and control (p=0.008) groups and with Okinawan vegetable intake in the dietary intervention group (p=0.0004).

Bone marrow as multidimensional orbit oscillator after autologous bone marrow transplantation.

The local renin-angiotensin system (RAS) in bone marrow is probably involved in the control of hematopoiesis. Earlier observations suggest the relationship between the frequency of sodium and potassium concentration changes in urine and bone marrow recovery after chemotherapy. The purpose of this study was to prove the relationship between sodium and potassium excretion changes in urine and granulocyte counts in peripheral blood after autologous bone marrow and peripheral blood stem cell transplantation. The correlation between amplitude maximum FFmax of F=d[Na]/d[K], where d[Na] and d[K] are changes of sodium and potassium excretions in 24 h, and granulocytes, recorded k days later, was found in 12 patients with autologous bone marrow transplantation (BMT) and/or PBSCT. In patients with successful engraftment, k ranged from 4 to 7 days. In the patient with unsuccessful BMT, k was 12 days. The results imply the interaction between systemic and bone marrow RAS.

Improvement of insulin sensitivity by short-term exercise training in hypertensive African American women.

African American women have a high prevalence of insulin resistance, non-insulin-dependent diabetes mellitus, obesity, and hypertension that may be linked to low levels of physical activity. We sought to determine whether 7 days of aerobic exercise improved glucose and insulin metabolism in 12 obese (body fat >35%), hypertensive (systolic blood pressure > or =140 and/or diastolic blood pressure > or =90 mmHg) African American women (mean age 51+/-8 years). Insulin-assisted frequently-sampled intravenous glucose tolerance tests were performed at baseline and 14 to 18 hours after the 7th exercise session. There was no significant change in maximal oxygen consumption, body composition, or body weight after the 7 days of aerobic exercise. The insulin sensitivity index increased (2.68+/-0.45 x 10[-5] to 4.23+/-0.10 x 10[-5] [min(-1)/pmol/L], P=.02). Fasting (73+/-9 to 50+/-9 pmol/L, P=.02) and glucose-stimulated (332+/-58 to 261+/-45 pmol/L, P=.05) plasma insulin levels decreased. Additional measures related to the insulin resistance syndrome also changed with the 7 days of exercise: basal plasma norepinephrine concentrations were reduced (2.46+/-0.27 to 1.81+/-0.27 nmol/L, P=.02) and sodium excretion rate increased from 100+/-13 to 137+/-7 mmol/d (P=.03); however, there was no change in potassium excretion or 24-hour ambulatory blood pressure. We conclude that a short-term aerobic exercise program improves insulin sensitivity in African American hypertensive women independent of changes in fitness levels, body composition, or body weight. The present study indicates that short-term exercise can improve insulin resistance in hypertensive, obese, sedentary African American women and confirms previous reports that a portion of the exercise-induced improvements in glucose and insulin metabolism may be the result of recent exercise.

The effect of spironolactone (Aldactone) on electrolyte balance and renal functions of calves

Skrzypczak W. F., K. Janus, Z. Muszczynski and D. Jankowiak: The effect of spironolactone (Aldactone) on electrolyte balance and renolfuncions of calves. Acta vet. Bmo, 63, 1994: 19-23. A short spironolactone test was carried out in a group of 10 clinically healthy calves at the age of 4 weeks. For 5 days (every 24 hours) the calves were administered Aldactone (Searle), per os, at a dose of 1 mglkg of body weight. Before the test began and 120 and 144 hours after giving the first spironolactone dose, the effective renal blood (ERBF) and plasma (ERPF) flow, and the glomerular filtration rate (GFR) were measured using sodium salt of p-aminohippuric acid and inulin. The levels of sodium, potassium and chlorides in plasma and erythrocytes were also determined. Some changes in the concentration of tested electrolytes were found in both the plasma and the intracellular fluid of erythrocytes. Changes in the renal function of calves were also indicated by an increase in effective renal plasma flow as well as by a decrease in glomerular filtration rate. Spironolactone, electrolyte b(llance, renal.fi!,nction, calves Calf kidneys are functionally efficient in the fIrst month oflife. However, they reveal some features of functional immaturity. These involve lowered effective renal blood (ERBF) and renal plasma (ERPF) flow,low glomerularfiltrationrate and low ability of urine concentration (Mercer etal.1978; Wanner etal.1981; Hartmann et al. 1987; Skrzypczak 1989; Skrzypczak etal. 1989; Skrzypczak 1991). The observed high tabular resorption ofNa, K and Cl in the frrst ~ days of life (Safwate et al., 1980; Skrzypczak, 1991) becomes lower as the age of calves increases (Safwate etal.1982; Skrzypczak 1989). The results of experiments show that, by the third day of life, mechanisms which control sodium resorption become active and kidney tubules respond to aldosterone infusion with the growth ofNa resorption (Safwate et al. 1980; Safwate et al. 1982; Itoh et al. 1985; Safwate 1985). Some authors, however, found a lack of correlation between the plasma renin activity and the aldosterone level, and sodium and potassium concentrations in the blood plasma (Siegler etal.1977; Moncaup etal.1980; Safwate etal.1982). Cabello (1980)evenreportsanegative correlation between plasma levels of aldosterone and sodium. Jankowiak (1989) showed that administering DOCA at a dose of 0.1 mglkg body weight Lm. caused a clearance drop and the urine excretion of sodium, potassium and chlorides also decreased. Safwate (1985) also noticed a lowering of sodium excretion in urine after aldosterone infusion, although he did not observe any changes in potassium excretion. Some authors indicate that there is a possibility of metabolic stimulation of the calf suprarenal glands in the first month of life (McEwan et al. 1968; Baranow-Baranowski etal. 1987). As can be seen from the literature review, there are many issues connected with tubular activity regulation in the postnatal period pertaining to electrolytes resorption which have not been fully explained yet (K a g a w a 1960; Bra u n Ii chand K e r s ten 1972; Cor v 0 I et al. 1981). The objective of this paper was to examine the effect of spironolactone (Aldactone) on electrolyte balance of body fluids and on glomerular filtration rate and effective blood and plasma flow through young calf kidneys. Materials and Methods The experiment was carried out on a group of 10 clinically healthy calves of cb. breed at the age of 4 weeks. They were kept in a calf-pen under constant, optimal conditions. Their left and right jugular vein had been catheterized and they had been weighed before the experiment began. Prior to the treatment period, the effective renal plasma (ERPF) and blood (ERBF) flow and the glomerular filtration rate (GFR) were defined. The levels of sodium, potassium and chlorides in blood plasma and erythrocytes were examined. To assess ERPF and GFR, sodium salt of p-aminohippuric acid (Serva-GmbH) and inulin (Sigma Chern. Co.) were used respectively. The clearance of these substances was measured using Bettge' s method. On the basis of ERPF and haematocrit, the amount of ERBF was defined and the filtration fraction (FF) was calculated. In order to block aldosterone activity, a short spironolactone test was conducted. The calves were administered 1 mglkg body weight of Aldactone (Searle) per os for 5 days. After 120 and 144 hours from giving the first dose of Aldactone, new examinations of ERPF, GFR values and Na, K and Cllevels in plasma and whole blood were carried out.

Chronic intrarenal hyperinsulinemia does not cause hypertension

Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.

Attributions for dietary failures: Problems reported by participants in the Hypertension Prevention Trial.

Assigned participants in the Hypertension Prevention Trial to one of four diets for a period of 3 years: (a) weight loss, (b) reduced sodium, (c) weight loss plus reduced sodium, and (d) reduced sodium plus increased potassium. At 6-month intervals, they reported problems they were having adhering to their diets. Problem attributions were coded along the dimensions of internality, stability, and controllability and were categorized as intrapersonal or extrapersonal. Attributions were found to differ by type of diet and sex of participant. Participants assigned to weight-loss groups were significantly more likely than those assigned to non-weight-loss groups to blame themselves for their problems with adherence, making characterological as opposed to external or situational attributions. Men perceived problems to be more controllable than women. Attributions did not predict weight loss, change in urinary sodium, or change in potassium excretion.

Hyperresponsiveness to atrial natriuretic factor in adult Brattleboro rats

Renal and hemodynamic effects of an intravenous infusion of atrial natriuretic factor (ANF) (8 μg/h) were studied in homozygous Brattleboro rats, which lack endogenous vasopressin. Heterozygous rats were used as controls. ANF-induced increases in sodium, chloride and volume excretion were higher, whereas changes in potassium excretion were lower in homozygous, as compared to heterozygous rats. The initial decrease in arterial blood pressure after ANF infusion was greater in the homozygous group, whereas there were no differential effects on heart rate. Inulin clearance, as well as clearance and fractional excretion of lithium were not significantly different between groups. The results indicate that Brattleboro rats show an exaggerated diuretic as well as saluretic response to ANF. They suggest that these effects are localized in the distal nephron and may be due to the known anatomical abnormalities in juxtamedullary nephrons of Brattleboro rats.

Effects of subpicomolar changes in vasopressin on urinary concentration.

The possibility that small amounts of vasopressin (AVP) reduce water excretion without affecting solute excretion was investigated in conscious dogs. AVP was infused intravenously for 120 min at rates of 2 and 5 pg.min-1.kg body wt-1 during water diuresis elicited by a sustained water load of 2% body wt. During control experiments urine osmolality was constantly approximately 60 mosmol/kgH2O; during AVP infusions it increased by factors of 1.36 (P less than 0.01) and 2.12 (P less than 0.01), respectively, concomitant with 39 +/- 6 and 61 +/- 7% reductions in urine flow. Osmolar and free water clearances decreased significantly. Sodium excretion did not change; changes in potassium excretion during AVP were similar to those of the control series, i.e., a gradual decline. During AVP, 5 pg.min-1. kg-1, creatinine and urea clearances decreased (25 +/- 2 and 31 +/- 7%, respectively, both P less than 0.01). With the assumption of metabolic clearance rates of AVP of 15-40 ml.min-1.kg body wt-1, the increase in plasma AVP during the infusion of 2 pg.min-1.kg body wt-1 was 5-13 X 10(-14) M. It is concluded that small increments in plasma AVP may reduce glomerular filtration rate and that with increasing levels of AVP in plasma 1) reduction of free water clearance, 2) reduction in urea clearance, and 3) natriuresis-kaliuresis occur in that order. Apparently AVP cannot reduce water excretion without changing the rate of excretion of solutes.

Plasma potassium and diurnal cyclic potassium excretion in the rat.

The relation of the plasma potassium concentration to the daily cyclic variation in potassium excretion was examined in undisturbed, unanesthetized male Sprague-Dawley rats maintained on a liquid diet in a 12-h light-dark environment. Potassium excretion increased from a light-phase minimum of 16 mu eq/h to a peak of 256 mu eq/h 3 h after the beginning of the dark phase. Plasma potassium concentration in arterial blood, sampled in rats at 90-min intervals during these changes in potassium excretion, showed no significant change and was in the range 4.50-4.99 meq/liter. In adrenalectomized rats receiving aldosterone and dexamethasone at constant basal rates by implanted pumps, the daily cycle of potassium excretion was the same as in the intact rats, and plasma potassium was not significantly different when measured at the time of minimum and maximum rates of potassium excretion (4.79 +/- 0.42 vs 5.16 +/- 0.47 meq/liter, mean +/- SD). These results indicate that plasma potassium concentration is not the efferent factor controlling diurnal cyclic changes in potassium excretion in adrenal intact rats and may not be the only significant factor in adrenalectomized-steroid replaced rats.

Interleukin-1 decreases renal sodium reabsorption: possible mechanism of endotoxin-induced natriuresis.

Administration of pyrogen or endotoxins such as Escherichia coli lipopolysaccharide can elicit a marked increase in urinary sodium excretion. This response occurs without any elevation in the filtered load of sodium and it does not appear to be prostaglandin mediated. The various effects produced by endotoxins appear to have interleukin-1 as a common mediator. In the present work, we have studied whether human recombinant interleukin-1 beta (hrIL-1) could affect the renal handling of sodium and thus, could be implicated in natriuretic response to pyrogens or endotoxins. We observed that hrIL-1 intravenously injected into conscious rats provokes a marked increase in sodium excretion. This natriuretic response was not associated with any increase in glomerular filtration rate (clearance of [3H]inulin), nor was it accompanied by significant changes in the urinary excretion of potassium, calcium, or inorganic phosphate. The only concomitant alteration was a decrease in urinary pH. Pretreatment with indomethacin abolished the effect of hrIL-1 on urinary pH but did not modify the natriuretic response. In conclusion, hrIL-1 elicits a selective decrease in tubular sodium reabsorption, which does not appear to involve a change in prostaglandin synthesis. This observation strongly suggests that interleukin-1 could be a key mediator in endotoxin-induced natriuresis.

Blood pressure response to dietary sodium restriction in normotensive adults.

Sixteen healthy, normotensive husband-wife pairs participated in a study to investigate the effect of reduction of dietary sodium intake (goal less than or equal to 60 mEq/day) on blood pressure. Sodium excretion decreased from a control average of 152.7 +/- 10.1 (SE) mEq/day to 69.5 +/- 4.5 mEq/day (p less than 0.001). Results indicated significant decreases in both systolic (p less than 0.001) and diastolic (p less than 0.001) blood pressure after a period of sodium restriction. In the entire group, there was no significant change in potassium excretion (58.4 +/- 3.2 vs 54.6 +/- 3.5 mEq/day) or body weight (76.0 +/- 2.8 vs 75.3 +/- 2.7 kg). Although there was variability in the blood pressure response, the decrease in blood pressure was significantly correlated with the magnitude of sodium restriction (r = 0.36, p less than 0.03). These results indicate that the blood pressure response to sodium restriction may not be limited to individuals with hypertension and that the response is heterogeneous in normotensive subjects.

Effects of inhibition of prostaglandin synthesis on fetal renal function

The role of renal prostaglandin production on the control of renal blood flow (RBF) and renal function was studied in eight chronically catheterized fetal lambs during the last trimester of gestation by using indomethacin as an inhibitor of prostaglandin synthesis. Following administration of indomethacin, RBF decreased significantly (-7.44 +/- 2.04 ml/min) whereas significant increases in filtration fraction (+3.92 +/- 0.85%) and renal vascular resistance (+ 0.41 +/- 0.13 mm Hg . ml-1 . min-1) were observed. Significant changes in glomerular perfusion rate were observed only in the inner portion of the cortex. No changes in GFR were demonstrated. Following administration of indomethacin, significant increases in fetal urinary sodium (+22.2 +/- 7.03 micro E/min) and chloride excretion (+18.2 +/- 6.26 micro E/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in Uosm (+100 +/- 25.9 mOsm/kg H2O) not associated with significant changes in urinary flow rate was also demonstrated following indomethacin. Finally, fetal administration of indomethacin produced a significant decrease in plasma renin activity (-2.70 +/- 0.65 ng/ml/hr) not associated with changes in plasma aldosterone concentration. The present data are consistent with the idea that prostaglandins are important modulators of RBF and renin secretion during fetal life. The inability of indomethacin to render the urine hypertonic indicates that the inability of the fetal kidney to concentrate is probably not due to endogenous activity of the renal prostaglandin system. The increase in sodium chloride excretion with a concomitant reduction of RBF is a pattern not previously reported following inhibition of prostaglandin production. In addition to their effects on RBF and renin release, renal prostaglandins in the fetal kidney may have tubular effects on sodium and chloride absorption that are opposite to those generally ascribed to adult kidneys.

Renal potassium excretion in sheep during sodium sulfate, phosphate, and chloride infusion

The renal excretion of potassium by unanesthetized sheep was studied in clearance studies in which water and sodium excretion were elevated by intravenous infusion of isotonic sodium chloride, hypertonic sodium phosphate, or hypertonic sodium sulfate. Aldosterone was infused at 10 microgram/h in some experiments with sodium sulfate. Sodium excretion increased in all experiments, rising at times to equal 25% of the filtered load. Urine flow increased in most experiments. Glomerular filtration rate increased only with infusion of isotonic saline. No consistent change in potassium excretion occurred under any of these loading conditions. This finding contrasts with the increase in potassium excretion commonly seen in man, dogs, and rats intravenously loaded with sodium salts.

Potassium Homeostasis

Potassium balance is regulated by appropriate changes in potassium excretion in the distal portion of the nephron. By contrast, potassium intake, absorption and proximal renal reabsorption do not show regulatory variation. Extracellular potassium concentration, which is a critical factor in membrane polarization, may at times vary in a direction opposite to total body content, because of altered distribution across cell membranes. Alterations in acid-base status frequently disturb homeostasis by altering potassium movement into cells, while insulin has an important regulatory effect on distribution. In general, the multiple renal and extra-renal mechanisms which prevent potassium overload are highly developed, while conservation is relatively ineffective. Consequently, depletion occurs more easily than spontaneous potassium overload. Homeostasis can be disturbed by renal impairment, excessive tissue breakdown, disturbances of acid-base balance, abnormal routes of loss, mineralocorticoid abnormalities and aberrations of sodium balance.

Antidiuresis produced by injection of renin into the third cerebral ventricle of the dog.

The purpose of this study was to determine whether centrally administered renin stimulated vasopressin secretion. Vasopressin was not measured directly, but, instead, changes in urinary water excretion in anesthesized dogs undergoing a water excretion in anesthetized dogs undergoing a water diuresis were used as an index of changes in vasopressin secretion. Intraventricular injection of hog renin in a dose of 0.1 Goldblatt unit produced a marked decrease in urine flow which was associated with a decrease in free water clearance and an increase in urinary osmolatiy with no change in osmolar clearance. Sodium excretion increased significantly but there was no change in potassium excretion. These effects, which closely resemble those resulting from an increase in vasopressin secretion, were prevented by hypophysectomy. The antidiuretic effect clearly resulted from an action of renin in the central nervous system since renin had no effect on urine flow or osmolality when administered intravenously. Intraventricular administration of saralasin acetate, a specific antagonist of angiotensin II, completely blocked the effects of intraventricular renin indicating that these effects were mediated via the formation of angiotensin II. The data therefore indicate that there is an interaction between injected renin, brain angiotensinogen, and converting enzyme resulting in the formation of angiotensin II which stimulates the secretion of vasopressin. Additional studies are required to determine whether the brain renin-angiotensin system plays a physiological role in the regulation of a vasopressin secretion.