7

Diuretics IIIChemistry, Pharmacology, and Clinical Applications

Proceedings of the Third International Conference on Diuretics, heldApril 2-7, 1989, in Mexico City, Mexico

Editor:

Jules B. Puschett, M.D.Professor of MedicineDirector, Renal-Electrolyte DivisionUniversity of PittsburghSchool of MedicinePennsylvania* UiS.A.

Associate Editor:

Arthur Greenberg, M.D.Associate Professor of MedicineMember, Renal-Electrolyte DivisionUniversity of PittsburghSchool of MedicinePennsylvania, U.S.A.

ElsevierNew York • Amsterdam • London

Contents

Preface xixSponsors xxiOrganizing Committee xxii

Section I: Diuretics 1

Human Studies

Combination d iuret ic therapy-furosemide with hydrochlorothiazide.Y. Or i ta, H. Nakahama, Y. Fukuhara, M. Yamazaki 3

Use of d iuret ics in the therapy of non-edematous disease states.H. Martinez-Maldonado 13

Effects of the osmotic d iuret ic mannitol on renal vein reninpro f i les . R.L. Benz, B.P. Teehan, H.H. Sigler , G.S. Gilgore,C. R. Schleifer 20

Effects of sodium intake on hemodynamic and tubular response tofurosemide in man. J .J . Beutler, W.H. Boer, E.J. Dorhout Mees 22

Chronic high dosage furosemide in haemodialysis patients.R.W. Van Olden, J.J.M. Van He i j e l , P.G.G. Gerlag 25

Comparison of the ef fect of bumetanide, furosemide and ethacrynicacid on the l i th ium clearance in humans. W.H. Boer, J .J . Beutler,E.J. Dorhout Mees 28

Effect of thiazides with and without carbonic-anhydrase inh ib i t i ngac t i v i t y on free water and l i th ium clearance. W.H. Boer, H.A.Koomans, E.J. Dorhout Mees 31

Effect of chronic oral furosemide administration on the 24-hourcycle in l i th ium clearance and electro ly te excretion in humans.S. Christensen, M. Shalmi, H. Rasmusen, 0. Amtorp 34

Metolazone plus furosemide: Evaluation of proximal Na+ reabsorptionby l i th ium clearance in nephrotic patients. P. Morachiello, S.Landini, A. Fracasso, F. Righetto, F. Scanferla, P.P. Tof fo le t to ,G. Bazzato 38

Discrepancy between two indices of d ista l del ivery, the l i th iumclearance and the maximal urine flow during furosemide in humans.J.J. Beutler, W.H. Boer 41

Resolution of hypercalciuria-associated hematuria with thiazidediuret ics in adult pat ients. A. Andres, M. Praga, J.M. Morales,J.L. Rodicio 44

Renal si te of action of muzoiimine in man. F.H. Noormohamed,A.F. Lant 46

Alterations in the metabolism of potassium and acid-base Eq.induced by stress in volunteers subjected to a chronic use offurosemide. G. Roberto, B. Andres 50

Effects of human albumin supplement on d iuret ic action offurosemide in patients with the nephrotic syndrome. T. Kawata,A. Ando, Y. Komatsu, R. Umezawa, N. Sugino 54

Renal function in elderly patients - influence of d i f fe ren td iure t ics . W. Muhlberg, H. Spahn, D. P la t t , K.O. Fehske,E. Mutschler 57

Modulation of urinary c i t ra te excretion (UCi) by promoting factorsof idiopathic urinary l i t h i a s i s . J.R. Weisinger, L. Aveledo,N. Pernalete, E. Bel lor in-Font, P. Durrego, G. Gonzalez,V. Paz-Martinez 60

Thiazide or indapamide in the treatment of tubular dysfunctionafter parathyroidectomy in primary hyperparathyroid pat ients.P. Morachiello, S. Landini, A. Fracasso, F. Righetto, F. Scanferla,P.P. Tof fo le t to , G. Bazzato 63

Effect of the loop d iuret ic torasemide on serum level and renalel imination of digoxin. B.K. Kramer, K.M. Rees, E. VonMoellendorf, L. Piesche, I . Achhammer, G.A. Muller, T. Risler 66

Instantaneous renal clearance derived by the UY mathematicalmodel. A.J. Reyes, W.P. Leary, K. Van der By! 69

The UY mathematical model of urinary f l u i d and solute continuousflows. A.J. Reyes, W.P Leary, K. Van der Byl 72

Increased urinary excretion of d iuret ics in hepat i t is pat ients.H. Knauf, H. Spahn, E. Mutschler 75

Low dose d iuret ic therapy: Significance of counterregulatorysystems. B. Weisser, B.O. Gobel, R. Pietsch, H. Vetter,R. Dusing 79

Hypocalciuric action of hydrochlorothiazide and PGE2. L. Caio,S. Cantaro, B. Baggio, A. D'Angelo, G. Bazzato, A. Borsatti 82

The effect of amiloride analogues on cerebral adaptation tochronic hypernatremic dehydration. H. Trachtman, R. del Pizzo,E.J. Cragoe, Jr 85

Pharmacokinetics of azosemide in patients with edema. H. Nakahama,Y. Or i ta , Y. Fukuhara, T. Kamada 88

Effects of a single high dose of piretanide on the excretion of Caand Mg in patients with different stage renal fai lure. A. Dorfler,W. Schulz, G. Ohrisch 91

Animal Studies

AY-31,906, A novel high ce i l ing d iuret ic with potassium-sparingproperties. D. M. Ackerman, A.G. MacLean, M.M. Brady, M. Kraml 94

Thromboxane A2 release during furosemide diuresis in the p ig.M. Cirano, C. Motz, A. Bussey, A.W. Ford-Hutchinson 97

Magnesium excretion during brisk diuresis in ra ts : Dependence ondiuret ic mechanism. M.J. F ie ld , J.S. Chrisp, J.R. Lawrence 101

Tubular albumin blunts the response to furosemide - a mechanismfor d iuret ic resistance in nephrotic syndrome. K.A. Kirchner,J.R. Voelker, D.C. Brater 104

Winter flounder urinary bladder as a model tissue for assessingthe potency of thiazide d iu re t i cs . J.H. L i , J.S. Zuzack, S.T.Kau 107

A novel potent d iu re t i c , M17055, having both loop and d is ta lactions. F. Yamasaki, T. Notsu, A. Kitamoto, T. Shinkawa, H.Inaba, E. Mochida, K. Yoshitomi, M. Imai I l l

Diuretic-induced hyponatraemia: Role of impaired tubular sodiumtransport versus ADH-mediated water retent ion. M. J . F ie ld , F.Seow, J.R. Lawrence 114

HOE 708, a novel d iuret ic with hypolipidemic propert ies. M. Hropot,C.H. Englert, E. Granzer, B. Von Kerekjarto, E. Klaus, H-J. Lang,W. Schol z 117

Stereospecif icity of the effects of ozolinone on renal haemo-dynamics and segmental tubular sodium reabsorption in consciousrats. J.S. Petersen, S. Christensen, M. Shalmi 124

Effect of chronic furosemide administration on urinary calciumexcretion and tota l body calcium in the ra t . S.N. Tuma, H. Evans,A. Leblanc, G. Eknoyan, W.N. Suki 127

In v i t ro -e f fec ts of various diuret ics on vascular eicosanoidmetabolism. B. Weisser, B.O. Gobel, G. Hoffmann, H. Vetter,R. Dusing 130

Cicletanine-induced phosphaturia and the k in in system. G.E. Plante,H. Pichette, D. Regoli 133

Effect of probenecid on loop diuret ic induced saluresis anddiuresis. R. Braitsch, E. Lohrmann, R. Greger 137

Effects of bumetanide on renal haemodynamics and tubular sodiumreabsorption in conscious rats. S. Christensen, M. Shalmi, J.S.Petersen 140

The si te and mechanism of action of S-8666, a novel uricosuricdiuret ic in the kidney. M. Nakamura, T. Shimizu, M. Imai 143

Effect of alpha-1 blockade (doxazosin) on proximal and d is ta ltubular response to furosemide-induced volume contraction inconscious ra ts . J.S. Petersen, M. Shalmi, U. Abildgaard,S. Christensen 146

Pharmacological p ro f i l e of DR-3438, a new uricosuric d iu re t i c .M. Tanaka, H. Hashimoto, S. Tanaka, M. Masumura, Y. Shirasaki,A. Akashi 150

Acid Base Interactions

Introductory Remarks: Diuretics and Acid-base balance.D.Z. Levine 153

Influence of pH on the natriuretic response to bumetanide andfurosemide. A. Greenberg, S.M. Ray, M. Shahawy, L. Vasillaros,J.B. Puschett 154

Use of amiloride as a model of distal renal tubular acidosisT.D. DuBose, Jr 160

Role of volume contraction and depletion of chloride and potassiumin the pathogenesis of saline-dependent metabolic a lka los is .S.H. Norr is, N.A. Kurtzman 167

Effect of loop diuret ics on urinary ac i d i f i ca t i on . W.A. Schlueter,D.C. Batl le 174

Use of piretanide in the evaluation of renal tubular ac id i f i ca t iona b i l i t y . H. Nakahama, Y. Fukuhara, Y. Or i ta , T. Kamada 183

Mechanism of Action

Characterization of the renal effects of xipamide in ra t s . J.Greven, A. Far jam 186

Investigations of the metolazone receptor. D.D. Fanest i l ,J.M. Trans,D.A. Vaughn, A.R. Maciejewski, K. Beaumont 195

Electrophysiologic studies of d iuret ic actions and relat ionshipsto calcium transport. Z.S. Agus, F. Ziyadeh, E. Kelepouris 205

The effects of the thiazide diuretics on calcium transport.S. Sabatini 212

Molecular actions of non carboxylic acid loop diuretics. J. Diez,N. Esparza, A. Arrazola 218

Piretanide inhibits the Na+2C1~K+ carrier in the thick ascendinglimb of the loop of henle and reduces the metabolic fuel require-ment of this nephron segment. P. Wangemann, R. Greger 220

The hypocalciuric effect of thiazides: Study of the mechanisms.M.G. Brunette, N. Harvey, J. Mailloux, I . Bouhitiauy,D. Lajeunesse 225

Complications of Therapy

Acid-base complications induced by diuretics. D.Z. Levine 228

The metabolic effects of diuretics: Relation to cardiovasculardisease risk factors. M.H. Weinberger 235

Triamterene crystalluria. P. Deetjen, A. Deetjen 241

The effects of diuretics on potassium and magnesium balance.

R. Solomon 245

Section I I : Other Therapeutic Agents 253

Converting Enzyme Inhibitors

Newer perspectives on angiotensin converting enzyme inhibit ion.B.J. Materson, R.A. Preston, J.R. Oster 255Effect of long-term enalapril therapy in Bartter's Syndrome.A. Andres, J.M. Morales, L.M. Ruilope, M. Praga, C. Prieto,J.L. Rodicio 265

Pharmacokinetic and pharmacodynamic interaction of perindopriland hydrochlorothiazide. C.L. Brown, J. Santoni, M. Devissaguet,P. Genissel 267

Direct action of angiotensin II and captopril on canine glomerularafferent arterioles. A. Hishida, K. Ohishi, R. Furuya,A. Kato, N. Honda 270

Serum albumin as a predictor of the antiproteinuric effect ofcaptopril in massive glomerular proteinuria. M. Praga, A. Andres,J.M. Morales, B. Borstein, J.L. Rodicio 273

Renal site of action of enalapril and enalaprilat. F.H.Noormohamed, A.F. Lant, W.R. McNabb, K.M. Koch, M. Hichens,V.J. Cirrilo, H.J. Gomez 275

Renal vasodilator response to captopril in the presence ofcalcitonin gene-related peptide (CGRP). S.M. Gardiner, A.M.Compton, T. Bennett 279

Calcium Channel Blockers

Nisoldipine influence on renal excretory and hemodynamicfunctions. M.L. Kauker, E.T. Zawada, R.J. Roman 282

Effects of the calcium channel blocking drug isradipine on renalfunction. T. Risler, M. Haussler, K.M. Ress, K.J. Burger, G.A.Muller, B.K. Kramer 285

Influence of calcium channel blocker treatment on earlycyclosporine nephrotoxicity in renal transplanation. A prospectivestudy. J.M. Morales, A. Andres, C. Prieto, C. Alvarez, B. Ortuno,B. Bornstein, M. Praga, T. Ortuno, J.L. Rodicio 288

Effect of nifedipine on the glomeruli in the kidney of thehypertensive rat. J.A. Christensen, B.M. Iversen, A. Bohle,M. Verho, J. Ofstad 290

Section I I I : Therapy of Sodium Retentive Disease States 293

Congestive Heart Failure

Diuretic use in congestive heart fai lure. D.A. Sica, T.W. Gehr 295

Renal effects of dobutamine and dopamine in congestive heartfai lure. R.C. Pabico, G.J. Rogal, B.A. McKenna, J.F. Richeson,W.B. Hood 302Continuous arteriovenous u l t ra f i l tration as diuretic maneuverin f luid overload. P.L. Oe, R.J.M. Strack van Schijndel,C.W.H. de Fi j ter, C.E. de Jong, J. van der Meulen 310

Comparison of piretanide/captopril and hydrochlorothiazide/captopril in hypertensive patients with moderate congestive heartfailure. R. Kirsten, H. Mauersberger, K. Nelson 313

Hemodynamic effects of piretanide and methyldigoxine in con-gestive heart failure—longterm results of a placebo-controlledrandomized double blind study. U. Bauer, W. Haerer, K.J. Fehske,N. Sultan, M. Hetzel 316

Diuretic monotherapy in congestive heart fai lure: Intermittentor continuous administration? B.-D. Gonska, K. Cao, K.-J. Fehske,H. Kreuzer 319

Acute and chronic effects of piretanide on the haemodynamics andvasopressure system in patients with aortic insufficiency andmitral stenosis. M. Schlepper, V. Mitrovic, F. Vens-Cappell,R. Kirsten, R. Pooth 322

Piretanide in the treatment of congestive heart fa i lure: A double-blind comparison versus furosemide. M. Verho, R. Bender, M. Hropot,B. Rangoonwala, W. Dol s 325

Controlled cl inical t r i a l to compare the efficacy and toleranceof torasemide and furosemide in patients with heartfai lure. R. Dusing, L. Piesche 328

Effect of torasemide on pulmonary and cardiac haemodynamics aftertreatment of chronic heart fa i lure. I . Achhammer, T. Podszus 331

Renal Failure

Management of hypertension in chronic renal fa i lure. P.C.Fernandez,M.H. Weiner, W.Y. Shih 334

No correlation between fenoldopam-induced natriuresis and changesin effective renal plasma flow. C.W.H. de F i j te r , E.F.I. Comans,P.L. Oe, J.C. Roos, A.J.M. Donker 342

Piretanide in mild and advanced renal fa i lure: Pharmacodynamicsand renal hemodynamics. H. Knauf, E. Mutschler, R. Pooth 346

Piretanide - A loop diuretic in the treatment of patients withrenal insufficiency. R. Pooth, K. Nelson, R. Kirsten 350

Acute effects of a high dose of piretanide on auditory function inpatients with chronic renal fa i lure. A. Dorfler, W. Schulz,G. Ohri sch 354

Saluretic effects of the loop diuretic torasemide in chronic renalfai lure. Interdependance of electrolyte excretion. H. Knauf,E. Mutschler 356

The load in the nephron segment determines the ceil ing qualityof a diuret ic. H. Knauf, E. Mutschler 359

Influence of piretanide on vasoactive prostaglandins,catecholamines, renin and aldosterone in patients with acuterenal fai lure. R. Kirsten, I . Rietbrock, T.D. Huber, B. Heintz,K. Nelson, R. Pooth 363

Cirrhosis

Peripheral arterial vasodilation as a major determinant of thepathogenesis of renal sodium retention in cirrhosis: Data froma model of experimental cirrhosis in rats. J.M. Lopez-Novoa 366

Physiological factors constraining the mobilization of ascites.M. Levy 376

Therapeutic strategies in the management of ascites. M. Epstein 383

Analysis of segmental tubular Na+ handling: A rational approachto the use of spironolactone in cirrhotic patients with ascites.J. Diez, M.A. Simon, J. Prieto 394

Comparison of the acute diuretic effect of torasemide andfurosemide in healthy subjects and in cirrhotic patients. G.Crippa, A. Cassi, R. Zurla, F. Vergani 396

Torasemide versus furosemide in cirrhosis. M. Zanazzi, G. Ratt i ,S. Ballocchi, L. Scarpioni 399

Treatment of cirrhotic ascities/edema: A therapeutic approach withtorasemide-spironolactone. G. Brunner, J. Chang, J. Gonzales,L. Piesche 402

Section IV: Hypertension 405

Human

Diuretics versus other agents in the therapy of primary (essential)hypertension. N.M. Kaplan 407

Salt restriction as adjunctive therapy in the treatment of hyper-tension. M.H. Weinberger, S.J. Cohen, J.Z. Miller, F.C. Luft,C.E. Grim, N.S. Fineberg 411

Calcium in the etiology of hypertension. P.C. Zemel, M.B. Zemel,J.R. Sowers 415

Epidemiologic factors in the pathogenesis of hypertension.J.A. Schoenberger 424

The kidney in essential hypertension: Pathophysiologic andtherapeutic implications. J.H. Bauer, G. Reams 431

Combined use of angiotensin converting enzyme inhibitors anddiuretics in the treatment of hypertension - physiological basisand clinical implications. C.V.S. Ram 440

Diuretics and other antihypertensive drugs in the treatment ofmalignant hypertension in children. G. Gordillo-PaniaguaL. Valencia, A. Arredondo 447

Therapy of hypertension in the black patient. E. Saunders 457

Therapeutic strategies for managing hypertension in the 1990's.A.F. Lant 466

Effects of bopindolol, atenolol, and propranolol on renal function.B.K. Kramer, K.M. Ress, G.A. Muller, T. Risler ;. 475

Acute effects of a loop diuretic on the renin-activity, Intra-cellular electrolytes and the blood pressure. C. Spieker,W. Zidek, K. Kisters, K.H. Rahn, H. Vetter 478

Low dose torasemide in essential hypertension. A.G. Dupont, D.F.Schoors, R.O Six, L. Vanhaelst 482

Alpha-adrenergic receptor blocking activity of verapamil accountsfor i ts additive depression of blood pressure in combined therapywith quinidine. E. Noack, A. Muller 485

Double-blind clinical t r ia l to compare the influence of torasemide2.5 mg/d and a combination of triamterene 50 mg/hydrochlorothiazide25 mg/d on serum-potassium during long term treatment of patientswith essential hypertension. P. Baumgart, I . Achhammer 488

Blood pressure control and control of body sodium handling areclosely related. Introducing the balance equation for systolicand diastolic blood pressure regulation. J. Myers 492

Relative effects of maxzide and hydrochlorothiazide on erythrocytecations and forearm vascular resistance. M.B. Zemel, P.C. Zemel,S. Bi j lani , B.A. Bedford-Johnson, J.R. Sowers 495

Animal Studies

Role of sodium in hypertension: Probes to detect sodium transportdefects in vascular smooth muscle. F.J. Haddy 498

Systemic hemodynamic, glomerular hemodynamic and non-hemodynamicfactors in the pathogenesis of glomerular injury in the sub-nephrectomized rat. R.Zatz, C.K. Fujihara 501

Role of glomerular hypertension in the progressive kidney damageof experimental hypertension. L.D. Dworkin, J.A. Benstein 507

Role of afferent and efferent resistances in hypertension inducedglomerular injury. J. Herrera-Acosta, E. Tapia, N. Bobadilla 515

Effect of furosemide and alpha-1 blocker on increased vascularcontractility in spontaneously hypertensive rats. Y. Takamitsu,S. Miki, H. Matsuo i 522

Phosphate metabolism and vascular reactivity: Interest of

indapamide. G.E. Plante, P. Sirois 525

Section V: Humoral Factors Affecting Sodium Transport 529

Atrial Natriuretic Factor

Role of atrial natriuretic factor in pathological states.A. Fernandez-Cruz, J.M. Lopez-Novoa, J. Gutkowska 531

Atrial natriuretic factor in the acute nephritic and nephroticsyndromes. D. Colic, B. Rodriguez-Iturbe, G. Parra, J.Gutkowska 538

Atrial natriuretic factor in extra-atrial tissues: Expression inlungs and olfactory mucosa. J. Gutkowska, M. Nemer, M.Marcinkiewicz, J.-P. Lavigne, M. Sole, J. Drouin, P. Sirois 543

Renal haemodynamic effects of peptides. S.H. Gardiner, A. M.Compton, T. Bennett 552

Biological and clearance receptors of atr ial natriuretic factor.D.R. Nussenzveig, B.M. Fontoura, A. Owada, T. Maack 560

Renal effects of atr ial natriuertic peptide in the human subject.M. Goldberg, M. Gehr 569

Modulation of ANF action by dietary salt manipulation.T.H. Steele 578

Renal hemodynamic effects of atr ial natriuretic factor. N. Honda,A. Hishida, K. Ohishi 584

Depression of cardiac sodium channel conductance by atrialnatriuretic peptide. J.O. Bustamante 589

Atrial natriuretic factor - adenosine interactions of renalhemodynamics and sodium excretion. S. Angielski, M. Redlak,M. Szczepanska-Konkel 595

Systemic hemodynamic and renal effects of atr ial natriureticpeptide in non-edematous patients. H.J. Kramer, H.G. Predel,H. Meyer-Lehnert 604

Atrial natriuretic peptide in liver cirrhotic patients. Effectsof head-out water immersion. L.M. Cuadrado, F.M. Gutierrez, J.M.Lopez-Novoa, J. Gutkowska, C. Loscos, J. Uson, A. Fernandez-Cruz 610

Effect of atr ial natriuretic hormone (hANP 102-126) infusions inpatients with congestive heart failure. I . DeScheerder, A.M.Standaert, A.M. Bogaert, R. Hombrouckx, D.L. Clement 613

The role of specific granules in ventricles on atrial natriureticpeptide secretion in acute heart fai lure. K. Satoh, T. Masuda,Y. Masaki, K. Ando, N. Hasegawa, T. Tsuyusaki, F. Marumo,R. Kikawada 615

Plasma atrial natriuretic peptide levels correlate with increaseof right atr ial area: The effect on plasma renin act ivi ty, plasmaaldosterone and plasma ADH during volume loading in healthyvolunteers. W. Wingender, D. Neuser, H. Weber, F.-J. Morich,R. Horstmann, J. Kuhlmann 618

High plasma a t r i a l nat r iu re t ic factor and early decrease in acutemyocardial in fa rc t ion . F.M. Gutierrez-Marcos, C. Herrero, F.Martin-Santos, J. Gutkowska, J.M. Lopez-Novoa, A. Fernandez-Cruz 623

Tubular blockade with a t r i a l na t r iu re t ic factor and angiotensinI I in volume-expanded dogs with isotonic saline or glucosesolutions. K. Honda, K. Matsuzaki, A. Nunokawa, M. Nagasaka 626

Compensatory ex t ra -a t r ia l secretion of a t r i a l nat r iu re t ic peptideduring cardiopulmonary bypass in man. N. Teran, G. Parra, B.Rodriguez-Iturbe, J . Gutkowska 629

Effect of dietary protein res t r i c t i on on the levels of a t r i a lnatr iuret ic peptide in insulin-dependent d iabet ics. C. Marin,G. Parra, J . Herrera, B. Rodriguez-Iturbe, J. Gutkowska 632

Effect of volume expansion on plasma a t r i a l na t r iu re t ic peptide inpatients with diabetes mel l i tus . J . Sanchez, F.M. Gutierrez,J.M. Lopez-Novoa, J. Gutkowska, M. Luque, J. Uson, L. Fernandez,A. Fernandez-Cruz 636

ANF receptors are d i f f e ren t l y regulated by ANF and angiotensin I I .P.E. Chabrier, P. Roubert, P. Plas, P. Braquet 639

Atr ia l nat r iu re t ic peptide and physical exercise in normal subjectsand in chronic renal fa i lu re patients. H. Jahn, D. Schohn, E.Schintgen, G. Rocha, C. Aysoy, S. Shaw, P. Weidmann 642

Is the d iuret ic e f fec t of methionine-enkephalin mediated by ANF?C. Coderre, B. Baranowska, J . Gutkowska 645

Other Natriuretic Factors

A humoral d i g i t a l i s - l i k e factor in man: Kinetic inferences for i t spossible role in nat r iures is . J. Hamlyn 648

Effects of brain nat r iu re t ic peptide on systemic hemodynamics inspontaneously hypertensive ra ts . T. K i ta , 0. Kida, T. Eto, KTanaka 65 7

Biological ac t i v i t y of a urinary nat r iu re t ic f ract ion of sa l tloaded human volunteers. M. Haberey i 660

Relationship between endogenous digoxin- l ike immunoreactivity,erythrocyte sodium pump, and hypertension in patients with chronicrenal f a i l u re . R.J. Bosch, N. Hernando, S. Casado, J.M. Lopez-Novoa 663

Section VI : Membrane Transport 665

Distal nephron effects of d iu re t i cs . G. Giebisch 667

Effects of d iuret ics on the ce l lu lar handling of potassium asanalyzed by electron microprobe analysis. F.X. Beck, T. Ring,A. Dorge, G. Giebisch, K. Thurau 678

Regulation of potassium channels in cultured renal epi theloid(MDCK) ce l l s . F. Lang, M. Paulmichl, F. Fr iedr ich, J.P fe i l sch i f te r , A. Jungwirth, C. Hallbrucker, P. Deetjen 685

Cholinergic stimulation of phosphoinositide hydrolysis in renalmedulla. L.C. Garg, S. McArdle 695

Phosphate uptake in human proximal renal tubule c e l l s .V.W. Dennis, J.P. Middleton, J.R. Raymond, C.B. Dunham, D. A.Sens 706

Effects of magnesium on the regulation of parathyroid hormone-dependent adenylate cyclase. E. Bel lor in-Font, C.L. Milanes,R. Starosta, C. Lopez, J.R. Weisinger, V. Paz-Martinez 716

Cytosolic magnesium as an inh ib i to r of potassium and chloridechannels in the loop of Henle. E. Kelepouris • 722

Effects of PGE2 on the in t race l lu la r calcium concentraton inep i the l ia l renal ce l ls (MDCK l i n e ) . M.G. Rodriguez, J.L. Reyes 730

Hypercalcemia and the cardiac membrane. F. Valenzuela 737

The tubuloglomerular feedback mechanism. A general overview.M. Franco Guevara, P.D. Bell 745

Macula densa ce l ls reabsorb NaCl via furosemide sensitiveNa -K+2CT- cotransport. E. Schlat ter, M. Salomonsson, A.E.G.Persson, R. Greger 756

Tubuloglomerular feedback in pathophysiologic condit ions. R.C.Blantz, S.C. Thomson, B. Tucker, F.B. Gabbai 759

Responses of the tubuloglomerular feedback mechanism to ACEinh ib i to rs and angiotensin I I . K.D. M i tche l l , L.G. Navar 764

Cellular magnesium handling during treatment with piretanide.K.J. Fehske, K, Kisters, A. Kwapisz, W. Zidek 770

Channel regulatory mechanism of sodium permeability in plasmatickidney membranes. Z.U. Beckmukhametova, I . I . Ismailov, E.L.Vol ynskaya 773

The luminal potassium channel in the thick ascending limb ofHenle's loop of ra t kidney. R. Greger, M. Bleich, E. Schlatter 776

Stimulatory actions of endothelin on the Na+, K+ pump[Na+, K+, Cl~] cotransport system in vascular smooth m

and themuscle cells

in culture. Involvement of cyclooxygenase products. C. Rosati,P.-E. Chabrier, M. Braquet, C. Nazaret, P. Braquet, R. Garay 780

Development of photoaffinity label of thiazide diuretic receptors.A.R. Maciejewski, K. Beaumont, D.A. Vaughn, D.D. Fanestil 783

Macromolecular piretanide inhibits the Na+-K+-2Cl"-cotransporterin the thick ascending limb of the loop of the Henle. R. Nitschke,E. Schlatter, 0. Eidelman, I. Cabantchik, H.J Lang, H.C. Englert,R. Braitsch, R. Greger 786

Uptake of bases across the basolateral membrane of rabbit kidneyproximal tubule. E. Brandle, J. Greven 789

Mechanism of action of thiazide diuretic netolazone on NaCltransport in the rat kidney tubule cel l . J.M. Tran, K. Beaumont,D.D. Fanesti 1 792

Renal and extrarenal mechanisms involved in body f luidhomeostasis: Role of the platelet-activiating factor. G.E.Plante, C. Prevost, P. Braquet, P. Sirois 795

Effects of DR-3438, t ieni l ic acid, indacrinone and furosemide onprimary cultured hepatocytes from rats. S. Takagi, S. Takayama,T. Onodera 800

Section VII : Endothelin 803

Cellular actions of endothelin and its plasma concentrations inpatients with abnormal vascular reactivity. H.J. Kramer, H.Meyer-Lehnert, H.G. Predel 805

Mechanism of calcium mobilization by endothelin in vascular smoothmuscle cel ls. H.E. Ives, R.C. Morris, Jr., T. Mitsuhashi 811

Endothelium-derived vasoactive medicators influence renal vascularand tubular functions. B.J. Ballermann, P.A. Marsden, A.J. King,E.R. Martin, M.L. Zeidel, S. Anderson, B.M. Brenner 820

The effect of endothelin on renal function and mesangial cellcontraction can be prevented by calcium antagonists. A. Lopez-Farre, I . Montanes, I. Mil las, M. Culebras, J.M. Lopez-Novoa 828

Author Index 831

Index 835