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Biomedical subjects

B M Brenner

Publications and source records attributed to B M Brenner.

At least 163 records · Page 9Linked to original sources
PubMed1988

Phosphorylation of a single subunit of the epithelial Na+ channel protein following vasopressin treatment of A6 cells.

Arginine vasopressin (antidiuretic hormone, ADH) stimulation of sodium transport in high electrical resistance epithelia is accompanied by adenylate cyclase stimulation and cAMP accumulation. The hypothesis of direct phosphorylation of the purified amiloride-blockable epithelial Na+ channel protein by cAMP-dependent protein kinase A after ADH treatment of cultured cells was investigated in this study. Phosphate-depleted A6 cells (a cell line derived from toad kidney) were exposed to 32PO4(3-) in the absence or presence of basolateral ADH (100 milliunits/ml). After 20 min (the time needed for ADH to increase maximally Na+ transport), the Na+ channels were extracted from the cells and purified. At every stage of purification, only one subunit of the Na+ channel, namely, the 315-kDa subunit, was specifically phosphorylated as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography or scintillation counting. In addition, a polyclonal antibody raised against purified epithelial Na+ channel protein was able to immunoprecipitate the phosphorylated channel protein from a detergent-solubilized fraction of vasopressin-treated A6 cells. This same subunit was also specifically phosphorylated in vitro when the purified Na+ channel protein was incubated with gamma-[32P]ATP and the purified catalytic subunit of the cAMP-dependent protein kinase. Thus, only a single component, the 315-kDa subunit, of the Na+ channel protein complex (which is composed of six subunits) can be phosphorylated both in vivo and in vitro. This subunit is selectively phosphorylated by the catalytic subunit of cAMP-dependent protein kinase to a level of 2-3 mol of 32P/mol of protein.

Animals↗
PubMed1988

Pathogenesis of diabetic glomerulopathy: hemodynamic considerations.

Early stages of diabetes mellitus are characterized by glomerular hyperfiltration in humans and experimental animals. In diabetic rats, single nephron hyperfiltration results from elevations in the glomerular capillary plasma flow rate and hydraulic pressure, which are in turn associated with progressive albuminuria and morphologic injury. Interventions that ameliorate these hemodynamic adaptations afford protection against structural injury. Dietary protein restriction, which lowers glomerular filtration, perfusion, and hydraulic pressure, retards glomerular injury and limits capillary basement membrane thickening in both the glomerular and retinal circulatory beds. Alternatively, selective control of glomerular capillary hypertension using angiotensin I converting enzyme inhibitor therapy limits glomerular injury in this model as well. Each of these interventions is effective even in the absence of improved metabolic control, implying that hemodynamic factors per se are important in this pathogenic process. The pathophysiologic mechanisms of diabetic hyperfiltration remain incompletely elucidated. Recent studies invoke a potential role for atrial natriuretic peptide (ANP). Strict metabolic control abolishes the elevations of glomerular filtration rate and of plasma ANP levels in moderately hyperglycemic diabetic rats. Moreover, infusion of a specific ANP antibody reverses hyperfiltration in diabetic rats. Thus, hyperglycemia-induced chronic volume expansion may trigger ANP release, which in turn contributes to diabetic hyperfiltration. Hemodynamic factors may play an important role in the pathogenesis of extrarenal microangiopathy as well. Elevated peripheral capillary blood flows and/or hydraulic pressure may be found in many peripheral capillaries, in association with thickening of the capillary basement membrane. Dietary protein restriction, which lowers blood flow to many organs, limits retinal as well as glomerular basement membrane thickening in diabetic rats, suggesting that hemodynamically mediated structural injury is a diffuse phenomenon in the diabetic state.

Animals↗
PubMed1988

Atrial natriuretic peptide and furosemide effects on hydraulic pressure in the renal papilla.

Atrial peptides (ANP) have been shown to preferentially increase blood flow to juxtamedullary nephrons and to augment vasa recta blood flow. To determine the effect of this alteration in intrarenal blood flow distribution on pressure relationships in inner medullary structures and their significance as a determinant of ANP-induced natriuresis, we measured hydraulic pressures in vascular and tubule elements of the renal papilla exposed in Munich-Wistar rats in vivo during an euvolemic baseline period and again during an experimental period. Rats in Group 1 received intravenous infusion of rANP administered as a 4 micrograms/kg prime and 0.5 microgram/kg/min continuous infusion, and were maintained euvolemic by plasma replacement. Infusion of ANP resulted in significant natriuresis, diuresis and increase in inulin clearance. Within 90 seconds of initiation of this systemic infusion, vasa recta hydraulic pressures were markedly increased and exceeded the small pressure increment occurring in loops of Henle and collecting ducts. Infusion of furosemide in Group 2 rats at a dosage which reproduced the increase in urine flow in Group 1 was associated with small and equivalent increases in both vascular and tubule elements, indicating that the differential pressure response observed in Group 1 was not due to increased tubule fluid flow rates, but was rather a specific ANP-induced vascular effect. Group 3 rats received an infusion of ANP in a setting where its whole kidney hemodynamic effects were prevented. This resulted in a marked blunting of natriuresis and diuresis, and obliteration of the pressure differential between vasa recta and tubules observed in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass.

Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, approximately equal to 42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (approximately equal to 30 vol/dl) by feeding a low iron diet or prevented (approximately equal to 50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12% of glomeruli, contrasted with 33% in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6% of glomeruli in rats with more severe anemia but progressed to 30% in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences.

Anemia↗
PubMed1988

Glucocorticoids amplify glomerular injury in rats with renal ablation.

Male Munich-Wistar rats were subjected to 1 2/3 nephrectomy. One group received no therapy (C). A second group received daily doses of methylprednisolone (MP). A third group received MP plus the angiotensin I converting enzyme inhibitor (CEI) benzazepril. A fourth group received CEI alone. Half of the rats in each group underwent micropuncture study 2 weeks after ablation. Untreated rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR), due to glomerular capillary hyperperfusion and hypertension. Administration of MP resulted in comparable systemic hypertension with further elevation of SNGFR due to even higher values for glomerular perfusion and hydraulic pressure (PGC). Concurrent treatment with CEI-controlled systemic and glomerular hypertension despite equivalent renal ablation and comparable doses of MP. After 12 weeks untreated rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI afforded striking protection against disease progression. Thus, potent vasodilator glucocorticoids may amplify hemodynamically mediated glomerular injury, whereas control of systemic and glomerular hypertension prevents this undesirable consequence of chronic steroid therapy.

Analysis of Variance↗
PubMed1988

Glomeruli and blood pressure. Less of one, more the other?

A primary role for the kidney in the initiation and maintenance of hypertension has long been recognized, but the pathogenetic interactions among renal hemodynamics, hormonal and hereditary factors, and dietary sodium intake remain enigmatic. Reduction in filtration surface area, whether acquired in the course of intrinsic renal disease or after surgical renal ablation, leads to systemic hypertension as well as to progressive renal insufficiency, sequellae made even more severe by dietary sodium excess. Moreover, hypertension and progressive renal disease eventuate in some individuals born with a solitary kidney, as well as in those with more severe degrees of dysgenesis (ie, oligomeganephronia). Hypertension is also commonly observed in certain inbred rat strains in which filtration surface area is congenitally deficient. Based on these and other lines of evidence reviewed herein, we postulate that a renal abnormality that contributes to essential hypertension in the general population is a reduced number of nephrons. The consequences of this abnormality are limitations in the ability to excrete sodium and thus, salt-sensitive hypertension. Finally, congenital variability in filtration surface area may explain why only some, but not all, patients exposed to potentially injurious renal stimuli eventually manifest chronic nephropathy. This may also account for the susceptibility of subsets of Type I and Type II diabetics to develop overt glomerulopathy.

Diabetic Nephropathies↗
PubMed1988

Therapeutic benefit of converting-enzyme inhibition in progressive renal disease.

Systemic hypertension is both the cause and the consequence of renal disease. Experimental studies suggest that the adverse effects of systemic hypertension on the progression of renal disease may depend upon the intraglomerular hemodynamic consequences. Systemic hypertension accompanied by afferent arteriolar vasoconstriction is associated with normal glomerular capillary pressure and relative protection against morphologic injury. In contrast, systemic hypertension with afferent arteriolar vasodilatation leads to glomerular hypertension and is associated with structural injury. Glomerular hypertension may be present even in the setting of normal systemic pressure, as in experimental diabetes. Therapeutic interventions that attenuate glomerular capillary hypertension slow the development of glomerular injury. Dietary protein restriction, which normalizes glomerular capillary filtration, perfusion, and pressure without lowering blood pressure, retards the development of glomerular sclerosis. Alternatively, selective reduction of glomerular capillary pressure with converting-enzyme inhibitor therapy is also protective against progressive renal injury. In contrast, antihypertensive therapy, which controls systemic hypertension but does not reduce glomerular capillary pressure, fails to protect remnant kidney rats from glomerular injury. These studies suggest that control of glomerular hypertension may be of special benefit to the patient with progressive renal disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Intraglomerular hypertension: implications and drug treatment.

Systemic hypertension is both cause and consequence of progressive renal disease. Recent experimental studies indicate that systemic and glomerular capillary hypertension are not necessarily accompaniments, and that therapeutic interventions may affect systemic and glomerular pressures independently. Therapeutic interventions that control glomerular capillary hypertension protect against progressive renal injury, even in the presence of continued systemic hypertension. Conversely, therapy that controls systemic but not glomerular hypertension does not protect the kidney from continuing damage. Thus, control of intraglomerular hypertension is necessary if antihypertensive therapy is to be effective in preventing progression of renal injury.

Animals↗
PubMed1988

Interrelationships among atrial peptides, renin, and blood volume in pregnant rats.

To determine how changes in intravascular volume are sensed by atrial and renal volume receptors during pregnancy and the puerperium, circulating atrial natriuretic peptide (ANP) levels and plasma renin activity (PRA) were measured in conscious chronically catheterized rats on days 9-10, 15-16, 19-20, and 22 of pregnancy, on the first postpartum day, and in nonpregnant controls. Blood volume measured in a separate group of anesthetized rats increased progressively during pregnancy, and circulating ANP levels tended to decline, although not significantly below the nonpregnant value of 132 +/- 9 pg/ml (mean +/- SE). PRA remained similar to the nonpregnant value of 5.5 +/- 0.6 ng angiotensin I.ml-1.h-1 until day 22 of pregnancy, when it rose to 14.1 +/- 1.8 ng angiotensin I.ml-1.h-1 (P less than 0.001 vs. nonpregnant). In pregnant rats, PRA was suppressed after uninephrectomy and chronic administration of deoxycorticosterone and saline, demonstrating the ability of this hormonal system to respond appropriately to further increments in volume induced during pregnancy. On the first postpartum day plasma ANP rose to 268 +/- 26 pg/ml, and PRA fell to 3.6 +/- 0.4 ng angiotensin I.ml-1.h-1 (P less than 0.005 and P less than 0.05 vs. nonpregnant values, respectively). Thus it appears that the increased blood volume in normal pregnancy is not sensed by renal or atrial volume sensors, presumably because it is accommodated by an enlarged maternal vascular compartment. In the puerperium, however, due to the decreased size of the maternal vascular compartment, atrial and renal volume sensors recognize the intravascular volume as expanded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Characterization of ANP receptors in rabbit inner medullary collecting duct cells.

The final urinary Na+ concentration is determined in the inner medullary collecting duct (IMCD) and is under hormonal control. In suspensions of IMCD cells we have previously shown that atrial natriuretic peptide (ANP) inhibits Na+ transport-dependent O2 consumption and causes an increase in cellular guanosine 3',5'-cyclic monophosphate (cGMP) content. In this study we sought to identify and characterize the receptor for ANP in these cells. Equilibrium binding studies revealed a single class of cell surface ANP receptors of high affinity (Kd = 66.2 pM) with a total number of 3,000 sites/cell. Specificity of these receptors was shown by the rank order of binding affinities for ANP analogues: ANP-(1-28) = ANP-(4-28) greater than ANP-(5-28) much greater than ANP-(5-25). We have further defined this receptor in a solubilized cell preparation and found it to be of molecular mass 130 kDa by affinity cross linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. This is the first characterization of an epithelial cell receptor for ANP; as in other systems this receptor appears to be linked to transport processes via the production of cGMP.

Animals↗
PubMed1988

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells.

Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Endogenous ANP augments fractional excretion of Pi, Ca, and Na in rats with reduced renal mass.

Atrial natriuretic peptide (ANP) infusion increases fractional excretion of many solutes including sodium, chloride, bicarbonate, phosphate, calcium, and magnesium. Because fractional excretion of these solutes increases with advancing renal disease, and because plasma ANP levels are known to be elevated in chronic renal failure, we sought to determine whether ANP mediates increased solute excretion rates per nephron in rats following extensive renal ablation, a model of chronic renal failure. Because sodium restriction decreases plasma ANP levels in the setting of reduced renal mass, we also determined the effect of sodium restriction on sodium, phosphate, calcium, and magnesium excretion rates in rats with 5/6 nephrectomy (NX). We also assessed whether high endogenous ANP levels influence fractional sodium, phosphate, calcium, and magnesium excretion in rats with 5/6 NX, by inhibiting ANP action via infusion of a high-affinity ANP antiserum. Whole-kidney glomerular filtration rate in 5/6 NX rats averaged approximately one-third that of shams, and plasma ANP levels were significantly elevated in these rats above those of shams, but to a lesser extent in rats on low- vs. high-salt intakes. Fractional sodium, phosphate, and calcium, but not magnesium excretion rates were significantly greater in 5/6 NX rats on the higher sodium intake compared with those in 5/6 NX rats on the lower sodium intake. Moreover, in 5/6 NX rats on the higher sodium intake, ANP antiserum significantly reduced fractional sodium, phosphate, and calcium excretion, but was without effect on magnesium excretion. These data implicate endogenous ANP in promoting the adaptive increase in sodium, phosphate, calcium, but not magnesium excretion per nephron in chronic renal disease.

Animals↗
PubMed1988

Atrial natriuretic peptides inhibit conductive sodium uptake by rabbit inner medullary collecting duct cells.

The inner medullary collecting duct (IMCD) effects net sodium reabsorption under the control of volume regulatory hormones, including atrial natriuretic peptides (ANP). These studies examined the mechanisms of sodium transport and its regulation by ANP in fresh suspensions of IMCD cells. Sodium uptake was inhibited by amiloride but insensitive to furosemide, bu-metanide, and hydrochlorthiazide. These results are consistent with uptake mediated by a sodium channel or Na+/H+ exchange. To determine the role of sodium channels, cells were hyperpolarized by preincubation in high potassium medium followed by dilution into potassium-free medium. Membrane potential measurements using the cyanine dye, Di(S)-C3-5 verified a striking hyperpolarization of IMCD cells using this protocol. Hyperpolarization increased the apparent initial rate of sodium uptake fourfold. Amiloride and ANP inhibited potential-stimulated sodium uptake 73% and 65%, respectively; the two agents together were not additive. Addition of 5 mM sodium to hyperpolarized cells resulted in a significant amiloride-sensitive depolarization. Half-maximal inhibition of potential-driven sodium uptake occurred at 3 X 10(-7) M amiloride, and 5 X 10(-11) M ANP. We conclude that sodium enters IMCD cells via a conductive, amiloride-sensitive sodium channel, which is regulated by ANP. ANP inhibition of luminal sodium entry in the IMCD appears to contribute to the marked natriuretic effect of this hormone in vivo.

Amiloride↗
PubMed1988

Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome.

Functional and morphologic measurements were performed in Munich-Wistar rats after a single central venous injection of puromycin aminonucleoside (PA) or saline vehicle (sham). During phase I, PA rats exhibited overt nephrotic syndrome and impaired glomerular filtration, primarily due to a reduction in the glomerular capillary ultrafiltration coefficient. The morphologic counterpart of the latter consisted of effacement of glomerular epithelial cell foot processes and decrease in the number of filtration slit diaphragms. Administration of the angiotensin I converting enzyme inhibitor (CEI) enalapril to PA rats did not ameliorate glomerular dysfunction. During phase II, PA rats exhibited spontaneous resolution of proteinuria, impaired function, and morphologic abnormalities. However, PA rats now demonstrated marked glomerular capillary hypertension and continued, albeit lesser, reductions in the ultrafiltration coefficient. Concurrent CEI administration modestly lowered systemic arterial pressure, and normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. Additional rats were studied during phase III, 70 wk after injection. In PA rats, prior glomerular hypertension was associated with development of recurrent proteinuria and extensive glomerular sclerosis, whereas concurrent CEI administration limited these parameters to values comparable to those in sham rats. Glomerular hypertension thus may explain the development of glomerular sclerosis and renal failure long after an episode of acute glomerular injury.

Animals↗
PubMed1987

Reversing glomerular hypertension stabilizes established glomerular injury.

Munich-Wistar rats were studied 18 weeks following 5/6 renal ablation. In untreated group 1 rats maintained on standard chow containing 24% protein, sustained systemic and glomerular hypertension were associated with increasing proteinuria and widespread glomerular injury. In group 2, early treatment with the converting enzyme inhibitor enalapril prevented systemic and glomerular hypertension, and largely limited proteinuria and glomerular injury. Groups 3 and 4 received no therapy during the first eight weeks, during which they developed systemic hypertension and levels of proteinuria previously shown to be associated with significant glomerular sclerosis at this time point. Enalapril therapy begun at eight weeks in group 3 rats reversed systemic and glomerular hypertension, prevented a further rise in proteinuria, and limited glomerular lesions at 18 weeks relative to group 1. Reduction of dietary protein content to 12% at eight weeks in group 4 rats controlled glomerular but not systemic hypertension to near-normal levels, stabilized proteinuria values, and also limited glomerular lesions at 18 weeks compared to group 1. These studies support the view that glomerular hypertension is an essential hemodynamic derangement responsible for progressive glomerular injury. Furthermore, reduction of capillary pressure can arrest the progression of remnant glomerular injury even when therapy is delayed until glomerular injury is established.

Animals↗
PubMed1987

Atrial natriuretic peptide transcription, storage, and release in rats with myocardial infarction.

To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.

Animals↗
PubMed1987

cGMP mediates effects of atrial peptides on medullary collecting duct cells.

Atrial natriuretic peptides (ANP) stimulate renal Na+ excretion by poorly understood mechanisms, possibly involving direct inhibition of Na+ transport in the renal medulla. We have previously shown that human ANP 4-28 (hANP) inhibits Na+ entry-dependent O2 consumption (QO2) in rabbit inner medullary collecting duct (IMCD) cells. Because ANP actions in other tissues appear to be mediated by guanosine 3',5'-cyclic monophosphate (cGMP), the present studies examined the role of cyclic nucleotides in IMCD cell responses to ANP. 8-Bromo-cGMP (8-BrcGMP) diminished QO2 by 23.5 +/- 1.2% (SE) in IMCD cells but had no effect in cells derived from outer medullary collecting duct (OMCD); dibutyryl-adenosine 3',5'-cyclic monophosphate (cAMP) was without effect in IMCD cells. The inhibitory effect of BrcGMP was not additive with ANP, amiloride, or ouabain. Amphotericin, which enhances Na+ entry into cells, prevented the inhibitory effect of 8-BrcGMP. These results indicate that 8-BrcGMP, like ANP, inhibited Na+ entry in IMCD cells. hANP stimulated a 10-fold increase in cGMP in IMCD cells without altering IMCD cAMP levels or OMCD cGMP levels. Isobutyl methylxanthine, which inhibits phosphodiesterase activity, enhanced both cGMP accumulation and inhibition of QO2 by submaximal levels (10(-9) M) of ANP. Nitroprusside raised cGMP levels in both IMCD and OMCD cells but inhibited QO2 only in IMCD cells. We conclude that cGMP mediates the transport effects of ANP in IMCD cells. Our results indicate that cGMP may play an important role in the regulation of sodium transport in renal epithelia.

1-Methyl-3-isobutylxanthine↗