Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control levels, maintaining metabolic alkalosis. In the late postfurosemide period, however, SNGFR returned to control levels in some instances. In these animals, both the filtered load and rate of proximal reabsorption were increased above the highest levels seen in control animals. The PCO2 gradient between the peritubular capillaries and arterial blood (Pc-Art) was significantly higher in CMA than in control, even though the rate of proximal bicarbonate reabsorption did not differ. Thus, proximal bicarbonate reabsorption did not appear to be the primary determinant of Pc-Art PCO2. PCO2 in the early proximal (EP) tubule was significantly higher than in either the late proximal (LP) tubule or peritubular capillaries in both control and CMA rats. The EP-LP PCO2 gradient correlated directly with proximal bicarbonate reabsorption (P less than 0.05). The small elevation in PCO2 in EP may be related to CO2 generated at this site in the process of bicarbonate reabsorption.

Load dependence of proximal tubular bicarbonate reabsorption in chronic metabolic alkalosis in the rat.

Studies were undertaken in Munich-Wistar rats to determine whether maintenance of chronic metabolic alkalosis (CMA) is associated with an increase in proximal HCO3- reabsorption, or whether a reduction in glomerular filtration rate (GFR) is required to sustain the elevated plasma HCO3- concentration. Superficial single nephron glomerular filtration rate (SNGFR), and absolute proximal HCO-3 (APRHCO3) and water (APRH2O) reabsorption were measured 20 +/- 3 d after the induction of CMA in eight rats and the results compared with seven age-matched control animals. Plasma [HCO3-] was 39.1 +/- 1.8 mM in CMA rats compared with 26.0 +/- 0.4 mM in controls (P less than 0.001). In the CMA rats, SNGFR was 44.8 +/- 1.1 vs. 38.2 +/- 2.1 nl/min in controls (P less than 0.025). As a result, the single nephron filtered load of HCO3- (FLHCO3) increased from 1,147 +/- 61 pmol/min in control to 2,040 +/- 108 pmol/min in CMA (P less than 0.001). APRHCO3 increased by greater than 65%, from 970 +/- 65 pmol/min in control to 1,624 +/- 86 pmol/min in CMA (P less than 0.001). APRH2O increased from 18.4 +/- 1.6 nl/min in control to 24.0 +/- 0.8 nl/min in CMA (P less than 0.005). Tubular hypertrophy resulted in an increase in the length of the proximal convoluted tubule from 5.6 +/- 0.2 to 6.5 +/- 0.2 mm (P less than 0.005). The pattern of HCO3- reabsorption along the length of the proximal convoluted tubule in CMA was indistinguishable from that found in normal rats in which FLHCO3 was varied acutely by altering SNGFR. The increase in tubular length accounted for only 30% of the increase in APRH2O and 15% of the increase in APRHCO3. We conclude that a sustained reduction in GFR is not required for maintenance of CMA in the rat. If GFR is chronically restored to normal levels, the alkalosis is maintained by an increase in APRHCO3. The increase in reabsorption is accounted for by tubular hypertrophy, a chronic adaptive response, and a load-dependent response that is indistinguishable from that seen in normal rats when FLHCO3 is increased acutely by increasing SNGFR.

Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis.

In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule (EP) is strongly dependent on delivery. Independent of delivery, metabolic acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated whether systemic pH changes induced by acute or chronic respiratory acid-base disorders also affect EP HCO3- reabsorption, independent of delivery (FLHCO3, filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h) and chronically (4-5 d) by increasing inspired PCO2. Hypocapnia was induced acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using hypoxemia to stimulate ventilation. When compared with normocapneic rats with similar FLHCO3, no stimulation of EP or overall proximal HCO3 reabsorption was found with either acute hypercapnia (PaCO2 = 74 mmHg, pH = 7.23) or chronic hypercapnia (PaCO2 = 84 mmHg, pH = 7.31). Acute hypocapnia (PaCO2 = 29 mmHg, pH = 7.56) did not suppress EP or overall HCO3 reabsorption. Chronic hypocapnia (PaCO2 = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was reversed when FLHCO3 was increased to levels comparable to euvolemic normocapneic rats. Thus, when delivery is accounted for, we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and, except at low delivery rates, no reduction in bicarbonate reabsorption in respiratory alkalosis.

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve.

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.

The nature of the renal adaptation to chronic hypocapnia.

Metabolic balance studies were carried out in normal dogs to define the renal mechanisms responsible for the adaptation to, and recovery from, chronic hypocapnia. A chronic reduction in arterial CO(2) tension (Pa(CO2)) of some 15 mm Hg was achieved by means of chronic exposure of the animals to 9% oxygen in an environmental chamber. The development of hypocapnia was associated with a marked suppression of net acid excretion which, together with a slight accumulation of organic acids, produced a reduction in plasma bicarbonate concentration (8 mEq/liter) that led to nearly full protection of extracellular pH (DeltaH(+) = - 2.5 nmoles/liter). When Pa(CO2) was returned to control levels, an augmentation of acid excretion restored plasma composition to normal after a brief period of "posthypocapneic metabolic acidosis."The changes in renal acid excretion during both adaptation and recovery were accomplished in a fashion notably different from that previously observed in chronic hypercapnia, being linked to changes in cation rather than chloride excretion. Thus, in dogs ingesting a normal NaCl diet, suppression of hydrogen ion excretion during adaptation to hypocapnia was associated with an increased excretion of sodium rather than with a retention of chloride. The fact that this loss of sodium occurred without a concomitant loss of potassium strongly suggests that the hypocapneic state specifically depressed distal sodium reabsorption; if distal sodium reabsorption had not been depressed, a reduction in proximal sodium reabsorption or a diminution in distal hydrogen ion secretion (or both) should have produced an increase in potassium excretion. The interpretation that chronic hypocapnia diminished sodium reabsorption was supported by the finding that when renal sodium avidity was enhanced by restriction of sodium intake, acid retention was accomplished by a loss of potassium rather than of sodium. The accompanying reduction in plasma bicarbonate concentration was slightly less than that observed in dogs ingesting a normal NaCl diet, a finding probably accounted for by a slight difference in the availability of cation for excretion under the two experimental circumstances. These findings, taken together with the observation that augmented acid excretion during recovery from hypocapnia is linked to cation retention, suggest that an adequate intake of cation during both adaptation and recovery from chronic hypocapnia may be critical to the physiologic regulation of acid-base equilibrium.

Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich-Wistar rat.

Studies were undertaken to characterize the pattern of proximal tubular fluid (APRH2O) and bicarbonate reabsorption (APRHCO3) in the remnant kidney of euvolemic Munich-Wistar rats. The remnant kidney rats were placed on a diet containing either low or normal protein. Collections were obtained in the early, mid-, and late proximal convoluted tubule. Single nephron glomerular filtration rate (SNGFR) increased from 40.2 nl/min in controls to 58.8 nl/min in low protein remnant kidney and 78.1 nl/min in normal protein remnant kidney rats. The filtered load of bicarbonate was 1,272, 1,641, and 2,013 pmol/min, in the three groups, respectively. APRH2O and APRHCO3 increased nearly in parallel. Most of the increase in reabsorption occurred in the early proximal tubule. Tubular hypertrophy could account for at least 20-40% of the increase in reabsorption, but the majority of the increase appeared to be a delivery-dependent response similar to that observed in normal rats after an acute increase in SNGFR.

A definition of proximal and distal tubular compliance. Practical and theoretical implications.

Micropuncture studies were carried out in the rat to evaluate the in situ distensibility characteristics of the proximal and distal tubules under a variety of experimental conditions. In the first phase, we determined the response of tubular diameter (D) to changes in tubular pressure (P) induced by partially obstructing single tubules. The response observed under these conditions (i.e., when interstitial pressure is presumed to be constant) has been defined as the compliance of the tubule. Over the range of tubular pressures studied (10-35 mm Hg for the proximal tubule, 5-25 mm Hg for the distal tubule) the compliance characteristics of the proximal and distal tubule were found to be markedly different; the proximal tubular pressure-diameter relationship was linear, DeltaD/DeltaP = 0.45 mum/mm Hg, whereas the distal pressure-diameter relationship was curvilinear, DeltaD/DeltaP = c(-0.1xP+2.2). In the second phase we used the compliance data to construct a series of theoretical pressure-diameter curves that define the response of the tubule to increments in interstitial as well as intratubular pressure. These curves indicate that changes in distal diameter should provide a sensitive index of a rise in interstitial pressure under conditions in which the transtubular pressure gradient is increased by a small amount, but that proximal diameter should provide a more sensitive index of changes in interstitial pressure when the transtubular pressure gradient is increased by a large amount. In subsequent experiments in which furosemide was administered, we observed that the pressure-diameter relationships for both the proximal and distal tubule were indistinguishable from the compliance curves, a finding consistent with the interpretation that interstitial pressure was not appreciably changed from control. By contrast, when mannitol was administered, both proximal and distal tubular pressure-diameter relationships were significantly altered in a fashion consistent with a large increase in interstitial pressure. Neither with furosemide nor mannitol administration did it appear likely that significant changes in tubular compliance could account for the observed behavior of the tubule.Finally, we propose that a knowledge of tubular compliance will be useful in exploring the interrelationships between tubular and peritubular pressures, tubular anatomy, and transtubular ionic permeability. Recent studies linking changes in the geometry of lateral intercellular spaces of the tubule to changes in passive ion movement suggest that an investigation of such anatomical-functional correlates should be productive.

Dependence of saline-induced natriuresis upon exposure of the kidney to the physical effects of extracellular fluid volume expansion.

In many previous studies, the natriuresis induced by saline loading has been demonstrated to persist even though glomerular filtration rate (GFR) has been decreased to below pre-expansion levels by a reduction in renal artery pressure. In such studies, however, the kidney has been exposed to the effects of volume expansion for varying periods of time before renal artery pressure was controlled. The present experiments were designed to evaluate whether this period of exposure induces critical changes in intrarenal factors that are responsible for the natriuresis.Experiments were carried out in rats, in which renal artery pressure was decreased to 70 mm Hg either at the onset of saline loading (immediate clamping experiments) or after 45 min of saline loading had elapsed (delayed clamping experiments). In the delayed clamping experiments, consonant with previous studies, mean sodium excretion, 3.2 mueq/min, remained markedly increased above control, despite a reduction in GFR to 91% of the hydropenic control value. In contrast, when renal artery pressure was comparably reduced at the onset of saline loading mean sodium excretion was only trivially increased, 0.4 mueq/min, although GFR increased to 140% of the hydropenic control value. These results exclude an important role for either a circulating hormone or a reduction in plasma oncotic pressure in the natriuretic response to saline loading, and indicate that intrarenal factors are the critical determinants of the natriuresis. We have used the difference in response to saline loading in the immediate and delayed clamping experiments to evaluate the role of two intrarenal factors, interstitial hydrostatic pressure and renal plasma flow. Interstitial pressure changes were estimated from changes in tubular pressure and diameter by using the in situ compliance characteristics of the tubules. In a group of rats saline loaded without aortic clamping, interstitial pressure increased by 4-5 mm Hg and renal plasma flow increased by 2.5 ml/min. During the period of reduced renal artery pressure, however, neither interstitial pressure nor renal plasma flow was detectably increased above control in either the immediate or the delayed clamping experiments. The only noteworthy difference between the experiments in which a natriuresis occurred (unclamped and delayed clamping studies) and the experiments in which no natriuresis occurred is that in the former group the kidney was at least transiently exposed both to an increase in renal plasma flow and interstitial pressure. These findings indicate, first, that extracellular fluid volume expansion can induce a natriuresis only if the kidney has been exposed to at least a transient increase in either interstitial hydrostatic pressure or renal plasma flow (or both); and, second, that a sustained increase in interstitial pressure and renal plasma flow is not required for the natriuresis to persist.

Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.

Studies were undertaken in Munich-Wistar rats to assess the influence of changes in filtered bicarbonate (FLHCO3), induced by changes in GFR, on Na+/H+ exchange activity in renal brush border membrane vesicles (BBMV). Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient-driven 22Na+ uptake in each animal studied. 22Na+ uptake was measured at three Na+ concentration gradients to allow calculation of Vmax and Km for Na+/H+ exchange. GFR was varied by studying animals under conditions of hydropenia, plasma repletion, and acute plasma expansion. The increase in GFR, FLHCO3, and APRHCO3 induced by plasma administration correlated directly with an increase in the Vmax for Na+/H+ exchange in BBMV. The Km for sodium was unaffected. In the plasma-expanded rats, the Vmax for Na+/H+ exchange was 22% greater than in the hydropenic rats (P less than 0.025) whereas APRHCO3 was 86% greater (P less than 0.001). These results indicate that increases in FLHCO3, induced by acute increases in GFR, stimulate Na+/H+ exchange activity in proximal tubular epithelium. This stimulation is a mechanism which can, in part, account for the delivery dependence of proximal bicarbonate reabsorption.

Hyperkalemia as a complication of drug therapy.

A wide array of drugs in common use can produce hyperkalemia. We reviewed our experience with severe hyperkalemia (potassium levels greater than 5.9 mEq/L [greater than 5.9 mmol/L]) in adult inpatients during a one-year period, to evaluate the extent to which drugs could be implicated in this electrolyte disorder. Excluding hemolyzed samples, single unexplained values, and measurements obtained during cardiopulmonary bypass or resuscitation, drug therapy was a probable contributing factor in more than 60% of the hyperkalemic episodes; in 25%, drugs were temporally linked to the onset of the hyperkalemia. In declining order of frequency, the drugs associated with hyperkalemia were potassium chloride, captopril, nonsteroidal anti-inflammatory agents, and potassium-sparing diuretics. In more than 80% of the drug-related hyperkalemic episodes, potassium regulation was compromised by underlying disease states. The most common was renal insufficiency, followed by diabetes mellitus and metabolic acidosis. This review underscores the dictum that caution should be exercised when drugs with hyperkalemic potential are used in patients with impaired potassium homeostasis.

End-stage renal disease. Measures to prevent it or slow its progression.

Studies conducted over the past 10 years have indicated that end-stage renal disease can be prevented or its progression slowed in many cases. Although prevention involves lifestyle changes, which many patients find difficult to make, strategies must be developed to help patients achieve the changes. Tight glycemic control in diabetic patients, control of blood pressure, and use of angiotensin-converting enzyme inhibitors are the essential features of the care needed to prevent renal failure.

Acid-base balance in dialysis patients.

Acid-base balance in dialysis patients is achieved by a unique interaction between the patient and the particular mode of renal replacement therapy. The prevailing serum HCO3- in these patients is determined not only by endogenous acid production but also by the nature of the dialysis prescription and, in particular, by the bicarbonate (or lactate) concentration of the bath solution. Despite the technical advances in dialysis therapy, pre-dialysis serum HCO3- remains lower than normal in most patients receiving hemodialysis and in many patients receiving peritoneal dialysis. A central question is whether even a mild degree of acidosis increases morbidity and mortality in patients with end-stage renal disease. This article reviews the nature of the acid-base equilibrium achieved in patients receiving hemodialysis or peritoneal dialysis, addresses the question of whether correction of acidosis is beneficial, and reviews the techniques for increasing serum HCO3- in these patients. Based on the information available, it is clear that the patient with a serum HCO3- less than 19 mEq/L should be assessed to determine the cause of the low value and steps undertaken to correct the acidosis. Whether patients with steady-state values between 19 and 24 mEq/L require specific attention remains an issue for further investigation.

Current concepts. Serum osmolality. Uses and limitations.

The serum osmolality measurement has a clearly circumscribed use in clinical medicine. Comparison of the measured osmolality with the osmolality calculated from the concentrations of the major solutes in serum gives information about large deviations in the serum water content. In addition, comparison of the measured and calculated values of osmolality provides rapid screening information about the presence of foreign low-molecular-weight solutes in the blood. Taken at face value, the test cannot be used to determine whether abnormalities in tonicity homeostasis are present. A simple and direct way to assess whether tonicity is normal is to calculate the effective osmolality from the concentrations of sodium and glucose in serum. With rare exceptions, this calculation provides the information needed to make decisions about therapy.

Atherosclerotic renovascular disease and progressive renal failure.

PURPOSE: To evaluate information on the prevalence and rate of progression of atherosclerotic renovascular disease and the effect of angiotensin-converting enzyme inhibition on this process, with the goal of developing a rational approach to the diagnosis and management of this disorder. DATA SOURCES: Relevant articles were identified from the authors' files and from MEDLINE searches. Additional references were obtained from the bibliographies of identified articles. STUDY SELECTION: Virtually no controlled prospective studies have been reported. The articles presented are primarily retrospective analyses and include those that provide sufficient information about the incidence or progression of renovascular disease and about the outcome and mortality rate associated with various treatments, to allow evaluation. DATA EXTRACTION: For the outcomes of interest, data from individual reports are presented in tabular form, the results summed, and averages obtained. RESULTS: Atherosclerotic renovascular disease, in many cases involving both renal arteries, is a common finding in patients older than 50 years, particularly those with diffuse atherosclerotic vascular disease. Hypertension is not a particularly sensitive indicator of this disease (almost one half are not hypertensive). The disease progresses and may account for 5% to 15% of all patients developing end-stage renal disease each year. Angiotensin-converting enzyme inhibition may damage ischemic renal tissue, but this is counterbalanced by beneficial effects of this therapy. Once end-stage renal disease is present, mortality rates are high despite dialysis support (> 50% over 3 years). Both surgery and angioplasty can preserve or improve renal function and may delay or prevent the need for dialysis therapy. These invasive procedures may have lower rates of morbidity and mortality than the so-called "conservative" approach of dialysis therapy when renal failure develops. CONCLUSIONS: Given available information, diagnosis and intervention should be considered seriously in patients at high risk for renovascular disease who have clearly progressing renal insufficiency. Prospective trials are needed, however, to determine the costs and benefits of each approach to treatment in all patients with renovascular disease and renal insufficiency.

Life-threatening hyperkalemia induced by arginine.

Marked hyperkalemia was observed during and immediately after an infusion of arginine monohydrochloride in two patients with severe hepatic disease and moderate renal insufficiency. Both patients had received brief courses of spironolactone before arginine treatment. In one of the patients, the hyperkalemia was associated with a fatal cardiac arrhythmia. Arginine has been shown to shift potassium from cells to the extracellular compartment, an effect directly related to its serum concentration. The profound hyperkalemia that occurred in these two patients is thought to be the result of an inability to metabolize the administered arginine and excrete the excess extracellular potassium. Caution is advised in administering arginine to patients with renal or hepatic insufficiency, or both.

Load dependence of HCO3 and H2O reabsorption in the early proximal tubule of the Munich-Wistar rat.

Studies were undertaken in Munich-Wistar rats to evaluate the influence of variations in the filtered load of bicarbonate (FLHCO3) and water [single nephron glomerular filtration rate (SNGFR)] on the pattern of reabsorption along the accessible proximal tubule. SNGFR and FLHCO3 were varied by examining animals under conditions of hydropenia, plasma and extracellular volume expansion (VE), and VE plus aortic constriction. Water and HCO-3 reabsorption rates were measured at intervals along the proximal tubule, from very early segments to late segments, and these values compared with previous measurements in euvolemic rats. The earliest accessible portion of the proximal tubule reabsorbed HCO3 and water avidly; 40-55% of FLHCO3 and 18-20% of SNGFR were reabsorbed within the first millimeter. Moreover, when FLHCO3 was increased to as high as 2,400 pmol/min, HCO3 reabsorption rate in the first millimeter of the tubule increased concomitantly, reaching values as high as 1,000 pmol X mm-1 X min-1. In a similar fashion, water reabsorption in the first millimeter increased in direct relation to increases in SNGFR, reaching values as high as 13 nl X mm-1 X min-1 at SNGFR values of 70 nl/min. These results indicate that the early proximal tubule has much higher HCO3 and water reabsorptive rates and a stronger load dependence than has been found in later segments of the proximal tubule. The early proximal tubule thus appears to play a critical role in the maintenance of glomerulotubular balance.

The early proximal tubule: a high-capacity delivery-responsive reabsorptive site.

The proximal convoluted tubule is responsible for reclaiming almost all of the filtered bicarbonate, glucose, and amino acids, as well as 40% or more of the filtered sodium, fluid, chloride, and phosphate. Walker and co-workers demonstrated the importance of this nephron segment as a high-capacity transport site in the first mammalian micropuncture studies, and they suggested that the first portion of the proximal tubule played a particularly important role in the ability of the nephron to adapt to variations in filtered load. Since then, many studies using micropuncture and in vivo and in vitro microperfusion techniques have confirmed that the early proximal tubule has a higher transport capacity than the late proximal tubule for a number of solutes. Moreover, at least for bicarbonate, fluid, and chloride, the transport capacity is not static, but is in a dynamic state, adapting in response to changes in filtration. In this review we have focused on the high capacity and load dependence of early proximal bicarbonate and fluid reabsorption. In addition, we summarize the evidence for axial heterogeneity along the proximal convoluted tubule for transport of a variety of other solutes.

Recent advances in the management of hypertension in the elderly.

Important new advances have occurred in our understanding and approach to management of high blood pressure in the elderly. New clinical trials have re-emphasized the risk of development of cardiovascular and cerebrovascular complications associated with isolated elevations in systolic blood pressure as well as the safety and efficacy of interventions to reduce blood pressure. These trials have shown that systolic blood pressure can be reduced by interventions such as weight loss, restriction of dietary sodium intake, and drugs. In several new trials, the long-acting dihydropyridine calcium channel blockers have been found to be safe and effective in these patients but not superior to other drugs. As in younger individuals with hypertension, drug therapy should be targeted to address comorbidity. Education of primary care physicians concerning these new findings is the next step in reducing the morbidity and mortality of this common problem in the elderly.