Changes In Plasma Potassium Concentration Research Articles

Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium.

Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms. Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage. A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .

No change in plasma potassium concentration during 10minutes of apnoea: An observational study on potential organ donors.

Acute acidosis can increase the plasma potassium concentration. However, data on the effects of acute respiratory acidosis on plasma potassium concentration are conflicting. This study aimed to determine whether acute respiratory acidosis induces an immediate increase in plasma potassium concentration. This observational study was conducted on participants undergoing apnoea testing prior to final radiological examination, registered in an internal quality registry at Oslo University Hospital between 25 April 2013 and 1 May 2020. A total of 124 donors were assessed for inclusion. Sixteen donors with blood glucose concentrations exceeding 10mmolL-1 were excluded; finally, data from 108 donors were included in the study. The apnoea test, which is a standard neurological test performed in potential organ donors prior to radiological confirmation of ceased brain circulation, induces respiratory acidosis. The arterial plasma potassium concentration, pH and PaCO2 before and after the apnoea test were compared. Statistical analysis was conducted using the paired t test. The pre-apnoea and post-apnoea mean plasma potassium concentrations were 3.79 (95% confidence intervals [CI] 3.70-3.87) and 3.79mmolL-1 (95% CI 3.70-3.88), respectively. The mean difference was -0.002mmolL-1 (95% CI -0.04 to 0.04); the difference was not significant. The pre-apnoea and post-apnoea mean pH were 7.39 and 7.21, respectively, and the mean difference was 0.175 (P<.01). The pre-apnoea and post-apnoea mean PaCO2 were 5.66 and 9.48kPa, respectively, and the mean difference was -3.83 (P<.01). Acute respiratory acidosis does not lead to rapid changes in plasma potassium concentration during apnoea testing in potential organ donors.

The association of acute hypercarbia and plasma potassium concentration during laparoscopic surgery: a retrospective observational study

BackgroundIt is uncertain whether increases in PaCO2 during surgery lead to an increase in plasma potassium concentration and, if so, by how much. Hyperkalaemia may result in cardiac arrhythmias, muscle weakness or paralysis. The key objectives were to determine whether increases in PaCO2 during laparoscopic surgery induce increases in plasma potassium concentrations and, if so, to determine the magnitude of such changes.MethodsA retrospective observational study of adult patients undergoing laparoscopic abdominal surgery was perfomed. The independent association between increases in PaCO2 and changes in plasma potassium concentration was assessed by performing arterial blood gases within 15 min of induction of anaesthesia and within 15 min of completion of surgery.Results289 patients were studied (mean age of 63.2 years; 176 [60.9%] male, and mean body mass index of 29.3 kg/m2). At the completion of the surgery, PaCO2 had increased by 5.18 mmHg (95% CI 4.27 mmHg to 6.09 mmHg) compared to baseline values (P < 0.001) with an associated increase in potassium concentration of 0.25 mmol/L (95% CI 0.20 mmol/L to 0.31 mmol/L, P < 0.001). On multiple regression analysis, PaCO2 changes significantly predicted immediate changes in plasma potassium concentration and could account for 33.1% of the variance (r2 = 0.331, f(3,259) = 38.915, P < 0.001). For each 10 mmHg increment of PaCO2 the plasma potassium concentration increased by 0.18 mmol/L.ConclusionIn patients receiving laparoscopic abdominal surgery, there is an increase in PaCO2 at the end of surgery, which is independently associated with an increase in plasma potassium concentration. However, this effect is small and is mostly influenced by intravenous fluid therapy (Plasma-Lyte 148 solution) and the presence of diabetes.Trial registration Retrospectively registered in the Australian New Zealand Clinical Trials Registry (Trial Number: ACTRN12619000716167).

Comparative dose response using the intravenous versus enteral route of administration for potassium replenishment

To compare the change in potassium concentration (dose-response) using the intravenous versus enteral route for potassium replenishment. Cross-sectional analysis of individual potassium chloride doses with resulting changes in plasma potassium concentrations in intensive care patients. Potassium chloride was administered according to potassium replenishment protocols. For inclusion, doses were required to have pre- and post-dose plasma potassium concentrations obtained within 8hours of administration. Medical and surgical intensive care units of a United States Veterans Affairs Medical Center. The primary outcome was the dose-response slope for intravenous versus enteral potassium administration as estimated by linear regression analysis. Multivariable linear regression was employed to adjust for potential confounders. The sample had 278 potassium chloride doses administered to 142 patients. The potassium concentration change per 20mmol of potassium chloride was similar for intravenous and enteral routes, 0.25mmol/L (95% confidence interval 0.16-0.33) versus 0.27mmol/L (0.15-0.39) respectively (p=0.73). Multivariable linear regression did not alter results. The success of achieving a minimum potassium concentration defined by the specific protocol was similar for intravenous (61%) and enteral (59%) administration. Overall, 77% of potassium chloride doses were administered at a time when patients were eligible to receive an enteral dosage form. The enteral route was as effective as the intravenous route in increasing the plasma potassium concentration. The enteral route was widely available for potassium replenishment. Despite enteral route availability and the well-known reliability of potassium chloride absorption, the majority of doses were administered intravenously.

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport.

Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.

The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized, multicentre trial

Succinylcholine provides rapid onset of neuromuscular blockade and short duration of action, but its administration may be associated with hyperkalemia. Rocuronium is not known to increase potassium concentration, has fast onset of activity, and can be rapidly reversed by sugammadex. This study evaluated changes in plasma potassium concentrations in patients randomized either to rocuronium followed by sugammadex reversal or to succinylcholine in ambulatory surgery. In this multicentre randomized active-controlled study, adult patients undergoing short surgical procedures in an outpatient setting received either rocuronium 0.6mg·kg(-1) for intubation with sugammadex 4.0mg·kg(-1) for reversal (n=70) or succinylcholine 1.0mg·kg(-1) with spontaneous recovery (n=80). Blood potassium concentrations were assessed at baseline (before study drug administration) and at intervals up to 15min after rocuronium, sugammadex, and succinylcholine. At the primary endpoint, five minutes post-administration, the changes in potassium concentrations from baseline were significantly smaller in patients treated with rocuronium than in those given succinylcholine [mean (SD): -0.06 (0.32) vs 0.30 (0.34)mmol·L(-1), respectively; P<0.0001]. At baseline, potassium concentrations were similar in both groups, but they were greater at two, five, ten, and 15min after succinylcholine than after rocuronium (P<0.0001) for all time points. After sugammadex administration, there were no significant changes in mean potassium concentration from the pre-rocuronium baseline. No adverse effects related to hyperkalemia were observed. Succinylcholine was associated with a modest increase in potassium concentration; these changes were not seen after rocuronium or sugammadex ( NCT00751179).

Plasma potassium-lowering effect of oral glucose, sodium bicarbonate, and the combination thereof in healthy neonatal dairy calves

Hyperkalemia is a common complication in neonatal diarrheic dairy calves and is corrected by administration of glucose or sodium bicarbonate. Although the hypokalemic effect of glucose is well established in other species, controversial results are reported for sodium bicarbonate. Our objective was to study the effect and mechanism of action of glucose and sodium bicarbonate on the potassium homeostasis of healthy neonatal dairy calves. Nine healthy neonatal Holstein-Friesian calves underwent 3 oral treatments with 2L of NaHCO3 (150mmol/L), glucose (300mmol/L), and glucose+NaHCO3 solution (300mmol/L+150mmol/L) in randomized order. Blood was obtained before treatment (T0) and at 30-min intervals thereafter. Changes between each time point and T0 were determined for all parameters. Urine was collected volumetrically to determine total renal potassium excretion over an 8-h posttreatment period. Plasma volume changes were extrapolated from changes in plasma protein concentration. Treatment and time effects were tested with repeated-measures ANOVA. Multivariate stepwise regression analysis using dummy variable coding was conducted to identify associations between changes in plasma potassium concentration ([K]) and changes in plasma glucose concentration ([glucose]), blood base excess, and plasma volume. Oral glucose and sodium bicarbonate treatments decreased [K] by 25 and 19%, respectively, whereas the combination of both compounds caused an intermediate [K] decline (22%). For the glucose treatment, the decline in [K] was only associated with changes in plasma [glucose] (partial R2=0.19). In NaHCO3-treated calves, [K] decline was associated with change of extracellular volume (partial R2=0.31) and blood base excess (partial R2=0.19). When glucose and NaHCO3 were combined, [K] decline was associated with changes in plasma volume (partial R2=0.30), BE (R2=0.22), and [glucose] (partial R2=0.03). Our results indicate that glucose lowers plasma [K] mainly through an insulin-dependent intracellular translocation of K, whereas NaHCO3 causes hypokalemia through hemodilution followed by intracellular translocation of K caused by the strong ion effect. The combination of glucose and NaHCO3 at the dosage used in this study does not have an additive hypokalemic effect. When combined, hemodilution and strong ion effect have the strongest effect on plasma [K], whereas the insulin-dependent effect of glucose appears to be blunted.

Plasma Potassium Concentration Changes Associated with Trimethoprim used for Urinary Tract Infections

ABSTRACTBackgroundHyperkalaemia has been reported with high‐dose trimethoprim (20 mg/kg/day) and standard‐dose trimethoprim (6 mg/kg/day) plus sulfamethoxazole use.AimTo investigate changes in plasma potassium concentrations in patients prescribed standard‐dose trimethoprim 300 mg daily for urinary tract infections.MethodA retrospective cohort study of hospital patients with urinary tract infections treated with trimethoprim or other antibacterials (control group) for more than 5 days. Plasma potassium concentration, creatinine and urea were compared at baseline and at the completion of treatment.ResultsThere were 31 patients in the trimethoprim group and 65 patients in the control group. End–of–therapy mean plasma potassium concentrations increased significantly from baseline in the trimethoprim group (4.2 ± 0.4 mmol/L to 4.5 ± 0.5 mmol/L; p = 0.002) but not in the control group. End–of–therapy mean plasma potassium concentrations were also higher in the trimethoprim group (4.5 ± 0.5 mmol/L vs 4.2 ± 0.5 mmol/L; p = 0.007). 65% of the trimethoprim group developed end–of–therapy hyperkalaemia versus 39% of the control group. Mean creatinine concentration in the trimethoprim group increased by an average of 21% from baseline but did not change in the control group. The trimethoprim group showed no change in mean urea concentration but a decrease was noted in the control group.ConclusionTreating urinary tract infections with trimethoprim 300 mg daily for more than 5 days was associated with an increase in plasma potassium concentration.

Narrative review: evolving concepts in potassium homeostasis and hypokalemia.

Humans are intermittently exposed to large variations in potassium intake, which range from periods of fasting to ingestion of potassium-rich meals. These fluctuations would abruptly alter plasma potassium concentration if not for rapid mechanisms, primarily in skeletal muscle and the liver, that buffer the changes in plasma potassium concentration by means of transcellular potassium redistribution and feedback control of renal potassium excretion. However, buffers have capacity limits, and even robust feedback control mechanisms require that the perturbation occur before feedback can initiate corrective action. In contrast, feedforward control mechanisms sense the effect of disturbances on the system's homeostasis. This review highlights recent experimental insights into the participation of feedback and feedforward control mechanisms in potassium homeostasis. New data make clear that feedforward homeostatic responses activate when decreased potassium intake is sensed, even when plasma potassium concentration is still within the normal range and before frank hypokalemia ensues, in addition to the classic feedback activation of renal potassium conservation when plasma potassium concentration decreases. Given the clinical importance of dyskalemias in patients, these novel experimental paradigms invite renewed clinical inquiry into this important area.

Changes in plasma potassium concentration during carbon dioxide pneumoperitoneum

Hyperkalaemia with ECG changes had been noted during prolonged carbon dioxide pneumoperitoneum in pigs. We have compared plasma potassium concentrations during surgery in 11 patients allocated randomly to undergo either laparoscopic or open appendectomy and in another 17 patients allocated randomly to either carbon dioxide pneumoperitoneum or abdominal wall lifting for laparoscopic colectomy. Despite an increasing metabolic acidosis, prolonged carbon dioxide pneumoperitoneum resulted in only a slight increase in plasma potassium concentrations, which was both statistically and clinically insignificant. Thus hyperkalaemia is unlikely to develop in patients with normal renal function undergoing carbon dioxide pneumoperitoneum for laparoscopic surgery.

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Effect of exercise-induced acidosis on aldosterone secretion in men.

The present study was carried out to elucidate whether an exercise-induced increase in plasma hydrogen ion concentration influences aldosterone secretion. Six healthy men (aged 22-25 years) performed two intermittent exercise tests with and without drug administration. The intensities of these exercise tests were 40% maximal oxygen uptake (VO2max) and 90% VO2max, respectively. Administration of 2-mg Dexamethasone and 50-mg Captopril caused an almost complete suppression of adrenocorticotropic hormone (ACTH) and an enhancement of the elevation in renin concentration during exercise, indicating successful inhibition of ACTH release and angiotensin II production during exercise. While the magnitude of the increase in aldosterone in the drug experiment was depressed compared with the control experiment, a significant increase in aldosterone concentration was observed at the end of the 90% VO2max exercise. Whilst the change in aldosterone concentration did not correlate with the change in plasma potassium concentration, there was a significant correlation between aldosterone and plasma hydrogen ion concentrations in the drug experiment. Since the correlation coefficient was low (r = 0.455), the biological meaning of this correlation should be further investigated. These results would suggest that an elevation of plasma hydrogen ion concentration induced by exercise per se appears to be related, at least in part, with increased aldosterone secretion, independent of the pituitary-adrenal axis, and the renin-angiotensin system.

Dissociation between water and lithium transport during acute changes in plasma potassium concentration in dog kidney

Lithium clearance is often used as a marker for proximal tubular water transport. Proximal tubular transport may be modulated by changing plasma potassium concentration. The aim of the present study was to examine the effect of acute changes in plasma potassium concentration on proximal tubular fluid and lithium transport. Clearance studies were performed in seven anaesthetised, volume-expanded dogs treated with amiloride (1 mg kg-1 body weight) to block distal tubular potassium secretion, and with bumetanide (30 μg kg-1 body weight) to inhibit sodium reabsorption in Henle's loop. When plasma potassium concentration was raised from 2.6±0.2 to 7.9±0.2 mmol 1-1, water reabsorption decreased from 23.9±2.9 to 19.8±2.2 ml min-1, whereas lithium reabsorption increased from 10.5±2.3 to 18.1±2.3 μmol min-1, at constant glomerular filtration rate. We conclude that acute elevation of plasma potassium concentration inhibits proximal tubular fluid reabsorption, but stimulates renal lithium reabsorption. Thus, lithium reabsorption cannot be used as a marker for proximal tubular transport during acute changes in plasma potassium concentration.

Potassium's cardiovascular protective mechanisms.

High rates of potassium intake are associated with protection from cardiovascular diseases in populations consuming primitive diets and in vegetarians living in industrialized cultures. In studies in humans and in animals, a strong inverse association between potassium intake and hypertension and stroke has been described. However, acceptance of the putative protective effect has been limited by inadequate understanding of 1) long-term potassium regulation, and 2) mechanisms by which small changes in plasma potassium concentration may affect development of cardiovascular diseases. In this review, we present results from analyses of long-term potassium regulation that indicated 1) changes in potassium intake may result in potassium concentrations from 3.1 to 4.6 mmol/l, and 2) when the initial rate is below normal, potassium concentration is very sensitive to changes in potassium intake rate. In addition, we present results that provide bases for possible mechanisms by which potassium may protect against cardiovascular diseases: 1) increases in potassium inhibit free radical formation from vascular endothelial cells and macrophages; 2) elevation of potassium inhibits proliferation of vascular smooth muscle cells; 3) platelet aggregation and arterial thrombosis are inhibited by elevation of potassium; and 4) renal vascular resistance is reduced and glomerular filtration rate is increased by elevation of plasma potassium. We propose that elevation of dietary potassium intake increases plasma potassium concentration, thereby inhibiting free radical formation, smooth muscle proliferation, and thrombus formation. As a result, the rate of atherosclerotic lesion formation and thrombosis will be diminished. In addition, we propose the increase in glomerular filtration rate will cause a shift in the relationship between arterial pressure and sodium excretion that will lead to a reduction in arterial blood pressure. By these actions, high levels of dietary intake of potassium could provide the observed protection against the cardiovascular diseases that have plagued humankind since we began eating a modern high-sodium, low-potassium diet.

Kinetics of plasma potassium concentrations during exhausting exercise in trained and untrained men

The purpose of this study was to examine the time course of changes in plasma potassium concentration during high intensity exercise and recovery in trained and untrained men. The subjects performed two exercise protocols, an incremental test and a sprint, on a cycle ergometer. A polyethylene catheter was inserted into the antecubital vein to obtain blood samples for the analysis of plasma electrolyte concentrations and acid-base parameters, during and after exercise. During both tests, venous plasma sodium, potassium and chloride concentrations increased in all the subjects, although the largest relative increase was detected in potassium concentration--35% and 31% over rest in the progressive test and 61% and 37.7% in the sprint test, for cyclists and controls, respectively. After exercise plasma potassium concentration decreased exponentially to below resting values. There was a linear correlation between the amount of potassium accumulated in plasma during exercise and the amount eliminated from plasma when the exercise ceased. We found that, although plasma potassium accumulation occurred in both forms of exercise in the trained and nontrained subjects, the time constant of potassium decrease following exercise was shorter in the trained subjects. Thus, the trained subjects exhibited a better capacity to recover to resting concentrations of plasma potassium. We propose that the extracellular potassium accumulation acts as a negative feedback signal for sarcolemma excitability depending on the muscle metabolic rate.

Kaliuresis in Normal Subjects following Oral Potassium Citrate Intake without Increased Plasma Potassium Concentration

Ingestion of potassium salts typically induces both a kaliuresis and an increase in the systemic plasma potassium concentration. In this study normal healthy adults undergoing water diuresis ingested potassium citrate or sodium citrate (0.5 mmol/kg body weight) or continued without ion ingestion (a time control group). Urine was collected over 20-min intervals and venous blood sampled at midinterval. Intake of potassium citrate led to a significant increase in potassium excretion that began during the first postingestion collection and peaked 60-80 min after intake with a maximal increase in potassium excretion above baseline of 1.60 mumol/min.kg-1. The kaliuresis occurred without changes in plasma potassium concentration, excretion of creatinine or calcium, or urine hypo-osmolality and was associated with a briefer, smaller, and less regular increase in sodium excretion and a pronounced but irregular increase in chloride excretion. Plasma aldosterone was insignificantly elevated above baseline, and the initial increase did not occur until 40-60 min after potassium intake. Intake of sodium citrate did not produce a kaliuresis. The cause of the kaliuresis does not appear to be an increased systemic plasma potassium concentration, an increased plasma level of aldosterone, intake of citrate, or an elevated excretion of sodium. The mechanism inducing the kaliuresis following oral potassium intake in the absence of changes in systemic plasma potassium may involve a reflex initiated at potassium sensors in gut, portal vein, or liver.

Angiotensin and angiotensin-converting enzyme inhibitors

The advent of the increasing use of different angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension and cardiac failure has resulted in intense interest in the renin-angiotensin system (RAS) and its manipulation for therapeutic gain, and thus more patients will present for surgical anaesthesia while on maintenance therapy with these agents. The RAS is increasingly described in terms of systemic and tissue components. The systemic component is important in maintaining cardiovascular and body fluid homoeostasis, and is activated through renin release by the juxtaglomerular cells of the kidney in response to signs of disequilibrium. Angiotensin I is formed from renin substrate and is converted by ACE to angiotensin II, the major mediator of this system, which in turn stimulates aldosterone release from the adrenal cortex. In addition, aldosterone can be released independently in response to changes in plasma potassium concentration. The release of these hormones is regulated through various feedback mechanisms. The role of the tissue RAS is not clear but has been found to be present in many organ systems and is increasingly seen as the major site of action of ACE inhibitor drugs. The first oral ACE inhibitor, captopril, introduced in 1977, was followed by enalapril (which can also be administered intravenously) and lisinopril. These agents inhibit the conversion of angiotensin I to angiotensin II. ACE inhibitors also inhibit the inactivation of bradykinin, a vasodilator, which in turn enhances vasodilatory prostaglandin formation. ACE inhibitors have been found increasingly useful in the therapy of hypertension and cardiac failure, and new indications for their use are under investigation. The effect of anaesthesia on the RAS has undergone limited study. Indications are that neither the RAS nor ACE are directly affected by anaesthetics. Preoperative therapy with ACE inhibitors has been associated with severe hypotension after induction of and during anaesthesia. In addition, the critical role of the RAS in the defence of blood loss is becoming apparent in patients receiving ACE inhibitors. In aortic surgery, however, ACE inhibition may be renoprotective, and experimentally these drugs have been shown to reduce myocardial infarct size after coronary occlusion in dogs. Thus, further studies are required to determine the exact role of ACE inhibitors in the perioperative period.

Mechanism underlying the changes in plasma potassium concentration during infusion of isosmotic nonelectrolyte solution.

Generally, during infusion of an isosmotic nonelectrolyte solution that permeates the cell membrane, plasma K+ concentration ([K+]pl) either does not change or it increases slightly. The mechanism underlying this [K+]pl change has not been clarified. We continuously monitored the [K+]pl and plasma Na+ concentration ([Na+]pl) for 10 min during isosmotic mannitol infusion of 1.6 ml/100 g body weight in rats with intact kidney function (intact mannitol group). In addition, in nephrectomized rats, we compared the [K+]pl change during infusion with isosmotic mannitol (which permeates the cell membrane; mannitol nephrectomized group) with that during infusion with isosmotic sucrose (which does not permeate the cell membrane; sucrose nephrectomized group) to evaluate the effect of cell volume regulation. In the intact mannitol group, [Na+]pl decreased with dilution, and [K+]pl remained relatively constant. In the sucrose nephrectomized group, [K+]pl decreased by the same percentage as [Na+]pl and gradually increased to greater than the control level. In the mannitol nephrectomized group, however, [K+]pl increased immediately after the beginning of the infusion and reached the same level as that in the sucrose nephrectomized group. To confirm that the difference in [K+]pl between the mannitol and sucrose nephrectomized groups was dependent on cell volume regulation, we investigated the changes in mean corpuscular volume of red blood cells, using a Coulter counter. This value remained constant during isosmotic sucrose infusion but increased during isosmotic mannitol infusion, returning to the original volume after the infusion. We kept [HCO3-] and pH constant throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Biphasic change in plasma potassium concentration by mannitol infusion in rats.

Changes in plasma Na+([Na+]pl) and K+([K+]pl) concentrations were continuously measured in nephrectomized rats consequent to intravenous infusion of isosmotic mannitol (M group) or sucrose (S group) at 1.6 ml/100 g body wt. for 10 min, and for the following 30 min. The effect of a Ca2+ channel blocker (diltiazem, 0.1 mg/100 g body wt.) was also evaluated. In the S group, [K+]pl decreased during the infusion and rose above the control level after the discontinuance of infusion. In the M group, [K+]pl gradually increased even during the infusion and reached the same level as the S group at the end of the experiment. In both the S and M groups, [Na+]pl decreased, while PaCO2, pH, and HCO3- did not change. The increase in [K+]pl in the M group had two components. The first was a transient component as presented by the difference of [K+]pl between the M and S group. It might be attributable to K+ release from the intracellular space during a regulatory volume decrease consequent to cell swelling induced by isosmotic mannitol infusion. The second component of the increase in [K+]pl after the infusion was observed in both groups, and this increase might be related to the dilution of ions induced by the large amount of infused nonelectrolyte solution. Diltiazem suppressed both of these changes in [K+]pl, suggesting that they are related to Ca2+ channels. The results suggest that increase in [K]pl by isosmotic mannitol infusion is related to the effects of regulatory volume decrease and dilutional effect.

Fluid-electrolyte shift and renin-aldosterone responses to exercise under hypoxia.

In order to describe fluid-electrolyte shift and endocrine response to exercise under moderate acute hypoxia, 8 healthy male subjects (24 +/- 3 years old) were evaluated at 40, 60, 80 and 100% VO2 max in normoxic (N) and hypoxic (H) conditions (14.5% O2). VO2 max decreased from 55.5 +/- 1.3 to 45.8 +/- 1.4 ml/kg X min in H condition. Plasma volume reductions with increasing relative workloads were similar in N (9.4%) and H (9.9%) conditions. The rise in plasma osmolality was in part related to blood lactate accumulation which occurred in both conditions. However, variations in plasma solute content and osmolality suggested that exercise under hypoxia results in a greater electrolyte loss from vascular space and in a greater K+ loss from working skeletal muscles. Increase in catecholamine concentrations were similar in normoxic and hypoxic conditions except for lower maximal norepinephrine concentration under hypoxia. Finally, although plasma renin activity increased with workload in both conditions, plasma aldosterone did not significantly change. This dissociation between renin and aldosterone suggest that aldosterone release during exercise might depend upon other factors. However, changes in plasma potassium concentration do not appear as an important stimulus for aldosterone secretion during exercise.