"There is power in the blood": a case discussing ethical issues of utility of resources.

The allocation of medical resources is often a great concern in the United States. This article discusses a case concerning utility of resources in a patient with a terminal disease. We assert that the goals of treatment tailored to an individual patient should be made at the bedside by a fiduciary (physician) in conjunction with the patient's preferences and values. There is great responsibility in making these decisions and it is critical that they be made at the bedside with the patient and family clearly aware of the goals of treatments and informed of treatment limitations.

Pressure natriuresis after adrenomedullin in anesthetized spontaneously hypertensive rats.

Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.

Nitric oxide, the kidney and hypertension.

1. According to the renal body fluid feedback mechanism for long-term control, persistent hypertension can only occur as a result of a reduction in renal sodium excretory function or a hypertensive shift in the pressure natriuresis relationship. Although an abnormal relationship between renal perfusion pressure and renal sodium excretion has been identified in every type of hypertension where it has been sought, factors responsible for this effect are still unclear. 2. Nitric oxide (NO) is produced within the kidney and plays an important role in the control of many intrarenal processes that regulate the renal response to changes in perfusion pressure and, thus, help determine systemic vascular volume and blood pressure. Numerous studies have shown that long-term inhibition of NO synthesis results in a chronic hypertensive shift in renal pressure natriuresis. 3. Recent studies have shown that certain animal models of genetic hypertension and forms of human hypertension areas are associated with a decrease in NO synthesis. Reductions in NO synthesis reduce renal sodium excretory function, not only through direct action on the renal vasculature, but through modulation of other vasoconstrictor processes and through direct and indirect alterations in tubular sodium transport. 4. The causes and consequences of the disregulation of NO in hypertension and other renal disease processes remain an important area of investigation.

Chronic sodium-potassium-ATPase inhibition with ouabain impairs renal haemodynamics and pressure natriuresis in the rat.

1. Chronic Na+, K(+)-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 micrograms day-1 kg-1 body weight) or vehicle for 6 weeks. 2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 +/- 2 mmHg; n = 9) than in control rats (116 +/- 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 +/- 73 microliters/min at 150 mmHg, and fell significantly to 322 +/- 64 microliters/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 +/- 0.2 compared with 0.29 +/- 0.2; P < 0.05). Renal blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 +/- 57.1 compared with 82.1 +/- 14.8 mumol min-1 mmHg-1). 5. Thus, chronic inhibition of Na+,K(+)-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25-30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.

Acute Na+,K+-ATPase inhibition with bufalin impairs pressure natriuresis in the rat.

Although it has been reported that Na+,K+-ATPase inhibition with bufalin induces acute and chronic hypertension in the rat, the mechanisms mediating this response are unclear. To examine the role of the kidney in this process, glomerular filtration rate, renal blood flow, and pressure natriuresis were determined in rats treated with bufalin or vehicle during changes in renal perfusion pressure. Mean arterial pressure increased from 123 +/- 4 to 149 +/- 3 mm Hg (P < .05) after 40 minutes of intravenous bufalin and remained at this level. In control rats, glomerular filtration rate was well autoregulated. In bufalin-treated rats, glomerular filtration rate fell with decreasing renal perfusion pressure. Glomerular filtration rate autoregulatory index was greater in bufalin-treated than control rats (P < .05). Renal blood flow showed a similar pattern. Urine flow and sodium excretion were less in bufalin-treated than control rats at equivalent renal perfusion pressures. The slope of the line describing the relation between urine flow and renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Similarly, the slope of the line relating sodium excretion to renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Thus, acute increases in blood pressure during Na+, K+-ATPase inhibition are associated with impaired renal autoregulation and pressure natriuresis. This effect may be important in chronic hypertension associated with Na+,K+-ATPase inhibition in the rat.

Dietary calcium supplementation restores pressure natriuresis responses in Dahl-S rats.

Calcium supplementation prevents hypertension in Dahl S (DS) rats. Because abnormal pressure natriuresis may contribute to the development of hypertension, we examined the effect of calcium on pressure natriuresis. DS and Dahl R (DR) rats maintained on a 4% sodium diet containing either 0.5% or 2% calcium for 4 weeks were anesthetized; sodium excretion, renal blood flow, and inulin clearance were determined at perfusion pressures of 100, 125, and 156 mm Hg. Inulin clearance and renal blood flow were not different between groups. Sodium excretion increased with increasing renal perfusion pressure in all groups. The slope of the line relating renal perfusion pressure to sodium excretion was greater (P < .05) in DR rats than in DS rats on normal calcium intakes. High calcium intake normalized the slope of the line relating renal perfusion pressure to sodium excretion in DS rats, but had no effect on DR rats. Thus, dietary calcium supplementation normalizes the blunted pressure natriuresis response in the DS rat and may contribute to the prevention of hypertension.

Endothelin antagonists improve renal function in spontaneously hypertensive rats.

Hypertension in the spontaneously hypertensive rat (SHR) is associated with reduced renal excretory function, low renal plasma flow, reduced glomerular filtration rate, and reduced renal interstitial hydrostatic pressure. The mechanisms responsible for these abnormalities in renal function are unknown. The purpose of this study was to determine the role of intrarenal endothelin in altering renal hemodynamic and excretory function in the SHR. Both PD 145065 (an endothelin A and B receptor antagonist) and FR 139317 (a selective endothelin A receptor antagonist) or saline was infused into the renal interstitium of 14- to 16-week-old SHR (n = 7) and age-matched Wistar-Kyoto rats (WKY) (n = 7). Renal perfusion pressure in some SHR was reduced to that of the WKY by a servocontrol system. At a renal perfusion pressure of 124 +/- 4 mm Hg, infusion of PD 145065. (0.03 mg.kg-1.min-1) and FR 139317 (0.02 mg.kg-1.min-1) significantly increased glomerular filtration rate (delta 22%), renal plasma flow (delta 37%), and renal interstitial hydrostatic pressure (from 3.2 +/- 0.5 to 5.4 +/- 0.6 mm Hg) in the SHR. These changes were associated with significant increases in urine flow, absolute sodium excretion, and fractional excretion of sodium. Similar improvements in renal plasma flow, renal interstitial hydrostatic pressure, and renal excretory function were obtained in the SHR whose renal perfusion pressure was not reduced (n = 7). Renal interstitial infusion of endothelin receptor antagonists had no effect on renal hemodynamic or excretory function in the WKY. These data demonstrate that endothelin receptor blockade within the kidney improves renal hemodynamic and excretory function in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials.

Segmental chloride transport in the Dahl-S rat kidney during L-arginine administration.

L-Arginine normalizes pressure natriuresis in Dahl salt-sensitive (DS) rats. The nephron segments responsible for improvement in sodium chloride handling during L-arginine administration are unknown. Micropuncture techniques were used to examine fluid and chloride transport along superficial nephron segments in DS rats maintained on an 8% sodium diet and given L-arginine or vehicle ip for 3 wk. Renal perfusion pressure in vehicle-treated DS rats was reduced to that of L-arginine-treated DS rats with an aortic snare. Dahl salt-resistant (DR) rats receiving vehicle were examined for comparison. In agreement with previous studies, urinary sodium chloride excretion was greater (P < 0.05) in L-arginine DS rats than in vehicle DS rats and not different from DR rats at equivalent renal perfusion pressures. Whole-kidney and single-nephron GFR were not different (P = not significant) among groups. Fractional proximal tubule chloride and fluid reabsorption was not different among groups. Fractional loop chloride reabsorption was greater in vehicle-treated DS rats than in DR rats (58.5 +/- 1.5 versus 46.6 +/- 1.7%; P < 0.05), confirming the enhanced chloride reabsorption at this location in DS rats previously reported. Fractional loop chloride reabsorption was identical in vehicle- and L-arginine-treated DS rats (58.4 +/- 1.4 versus 58.9 +/- 3.9%; P = not significant). Fractional loop fluid reabsorption was not different among groups. Fractional distal fluid and chloride reabsorption was not different between DS rat groups.(ABSTRACT TRUNCATED AT 250 WORDS)

L-arginine improves transmission of perfusion pressure to the renal interstitium in Dahl salt-sensitive rats.

L-Arginine normalizes pressure natriuresis in Dahl salt-sensitive (DS) rats. To determine the role of renal interstitial hydrostatic pressure (RIHP) in this phenomenon, we measured RIHP determined by servo-null during acute changes in renal perfusion pressure in anesthetized DS rats receiving L-arginine (300 mg.kg-1.day-1 ip) or vehicle for 3 wk. Dahl salt-resistant (DR) rats were controls. As observed previously, the slope of the pressure-natriuresis relationship was greater (P < 0.05) in L-arginine-treated DS rats than vehicle DS rats and not different from DR rats. The slope of the relationship between renal perfusion pressure and RIHP was greater (P < 0.05) in DR rats than vehicle DS rats. In L-arginine-treated DS rats the slope of this relationship was greater (P < 0.05) than that in vehicle DS rats and not different from DR rats. Removal of the renal capsule blunted the pressure-natriuresis relationship in L-arginine-treated DS rats but had no effect in vehicle DS rats. Thus L-arginine improves transmission of perfusion pressure into the renal interstitium in DS rats and may contribute to the improved pressure-natriuresis response.

Decreased sensitivity to renal interstitial hydrostatic pressure in Dahl salt-sensitive rats.

The ability of Dahl salt-sensitive (DS) rats to excrete a sodium load is significantly lower than Dahl salt-resistant (DR) rats. Because renal interstitial hydrostatic pressure (RIHP) is a major mediator of natriuresis in response to a sodium load, we proposed that the renal tubules of DS rats are less responsive to increases in RIHP than those of DR rats. To test this hypothesis, we determined the effect of direct increases in RIHP on renal excretory function in prehypertensive DS and DR rats. RIHP was directly increased by renal interstitial volume expansion via injection of 50 microL of a 2% albumin and saline solution into the renal interstitium through a chronically implanted renal interstitial catheter. RIHP, mean arterial pressure, glomerular filtration rate, urine flow rate, urinary sodium excretion, and fractional excretions of sodium, potassium, and lithium (an indicator of proximal tubule sodium handling) were measured before and after direct increases in RIHP in DS (n = 8) and DR (n = 8) rats. Baseline urine flow rate; urinary sodium excretion; fractional excretions of sodium, potassium, and lithium; RIHP; mean arterial pressure; and glomerular filtration rate were not different between DS and DR rats. Renal interstitial volume expansion in DS rats significantly increased RIHP (delta 4.7 +/- 0.8 mm Hg), urine flow rate (delta 14.5 +/- 3.4 microL/min), urinary sodium excretion (delta 2.62 +/- 0.62 mumol/min), and fractional excretions of sodium (delta 1.54 +/- 0.37%), potassium (delta 17.84 +/- 2.90%), and lithium (delta 19.68 +/- 3.52%).(ABSTRACT TRUNCATED AT 250 WORDS)

Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention.

OBJECTIVE: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. METHODS: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. RESULTS: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressure in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. CONCLUSION: Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.

The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

OBJECTIVE: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. METHODS: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months. RESULTS: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure. CONCLUSION: Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women.

L-arginine administration normalizes pressure natriuresis in hypertensive Dahl rats.

A blunted pressure-natriuretic response characterizes hypertension in the Dahl salt-sensitive rat. Long-term L-arginine administration prevents hypertension in these animals. To determine if long-term L-arginine corrects the pressure-natriuretic response, we gave salt-sensitive rats on an 8% sodium diet L-arginine or vehicle daily for 3 weeks. Identically treated salt-resistant rats served as controls. After 3 weeks, acute pressure-natriuresis curves were determined. To control for hypertension-induced renal damage, we also examined pressure natriuresis in salt-sensitive rats after short-term L-arginine. Baseline mean arterial pressure was 158 +/- 3 mm Hg in vehicle-treated salt-sensitive rats and 127 +/- 3 mm Hg in chronically L-arginine-treated salt-sensitive rats. During alterations in perfusion pressure, renal blood flow was autoregulated in all groups. Glomerular filtration rate was autoregulated in salt-resistant rats and L-arginine-treated salt-sensitive rats but fell with decreasing pressure in vehicle-treated salt-sensitive rats. Sodium excretion was greater (P < .05) in L-arginine-treated than in vehicle-treated salt-sensitive rats and did not differ from salt-resistant rats at 100, 125, and 158 mm Hg. The slope of the pressure-natriuresis relation was greater (P < .05) in chronically L-arginine-treated than in vehicle-treated salt-sensitive rats. L-Arginine had no effect on natriuresis in salt-resistant rats. Thus, long-term L-arginine administration normalizes pressure-natriuretic responses in salt-sensitive rats. The effect is not due to the prevention of renal damage and is specific to the salt-sensitive strain.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of percutaneous renal biopsy in clinical nephrology.

Percutaneous renal biopsy provides the cornerstone for our understanding of the diseases of the kidney. Recent advances in biopsy techniques, such as the use of real-time ultrasonography and the biopsy gun, have made this procedure easier, increased the yield of diagnostically adequate tissue, and may result in a lower complication rate as well. Despite these improvements, the role of biopsy in the treatment of individual patients remains controversial. Even in diseases such as nephrotic syndrome and systemic lupus erythematosus, where biopsy findings have been used to categorize outcome events, it is unclear whether the biopsy provides more accurate information than can be obtained from less invasive procedures or from empiric therapy. Renal biopsy, however, does remain the best method for evaluation of renal dysfunction in renal allograft recipients. The role of fine-needle aspiration cytology in the management of transplant rejection remains to be established.

Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats.

This study examined the contribution of endothelium-derived relaxing factor (EDRF) to the susceptibility of uninephrectomized rats to deoxycorticosterone acetate (DOCA)-salt hypertension. N omega-nitro-L-arginine, a probe for EDRF, produced smaller increases (P < 0.001) in mean arterial pressures in anesthetized hypertensive DOCA-salt rats than in sham rats. Acute L-arginine administration (300 mg/kg body wt i.v.) failed to reduce pressure in anesthetized DOCA-salt rats. Chronic oral and intraperitoneal L-arginine did not lower pressure in conscious DOCA-salt rats with established hypertension, nor did it prevent hypertension when begun in prehypertensive DOCA-salt rats. Preconstricted aortic rings from DOCA-salt rats had attenuated relaxation to acetylcholine compared with sham rats. Rings L-arginine-treated DOCA-salt rats had responses similar to DOCA-salt rats. Relaxation to nitroprusside was not different between any rat group. Thus EDRF is attenuated in DOCA-salt hypertension. However, unlike several other hypertensive models, the blunted EDRF response cannot be overcome by provision of L-arginine. These data suggest synthesis or release of EDRF may be noncompetitively inhibited in DOCA-salt hypertension.

Verapamil prevents insulin antinatriuresis in euglycemic rats.

To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.

Increased loop chloride uptake precedes hypertension in Dahl salt-sensitive rats.

When studied at equivalent renal perfusion pressures, loop segment chloride reabsorption is greater in hypertensive Dahl salt-sensitive (S) than Dahl salt-resistant (R) rats. To determine whether this difference in loop reabsorption is present before the onset of hypertension, volume expanded and euvolemic Dahl rats maintained on low NaCl diets were examined using micropuncture and in vivo microperfusion techniques. Neuroendocrine differences between groups were eliminated by renal denervation and fixing plasma aldosterone, norepinephrine, and vasopressin levels. After volume expansion, urinary NaCl excretion was less in S than R rats. Early distal tubule fluid-to-plasma chloride and inulin (TF/PCl/IN) ratio and chloride delivery were also less while loop chloride reabsorption was greater in S rats. Proximal delivery was not different between groups. In euvolemia, urinary NaCl excretion and loop chloride reabsorption were not different between S and R rats. However, when loop chloride delivery was increased by microperfusion techniques, lower distal TF/PCl/IN ratios and greater loop chloride reabsorption were clearly demonstrated in euvolemic S rats. Thus loop chloride reabsorption is greater in S than R rats before the development of hypertension. This difference depends on increasing delivery rates for its manifestation.

Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats.

A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)