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1-225 Renal Response to Amino Acid Infusion in Essential Hypertension Luis Juncos, Juan Carlos Cornejo, Encaraacion Pamies-Andreu, Juan Carlos Romero Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 Abstract In the present study, we evaluated the renal response to a 4-hour infusion of amino acids in essential hypertensive patients, as well as the effects that dietary sodium restriction and enalapril (a converting enzyme inhibitor) had on this renal response. During normal sodium intake, amino acid infusion significantly increased renal plasma flow from 383±58 to 478±51 mL/min and glomerular filtration rate from 82±8 to 100±13 mL/min. All these effects were abolished when the patients received a low sodium diet (40 mmol/d) for 3 days before the amino acid infusion. The administration of enalapril to the patients during sodium restriction restored the amino acid-induced increment in renal plasma flow (from 388±35 to 537±48 mL/min) and glomerular filtration rate (from 88±9 to 103±10 mL/min). Mean arterial pressure remained unaltered under all experimental conditions. The results show that in patients with essential hypertension dietary sodium restriction prevents amino acid-induced increments in glomerular filtration rate and renal plasma flow and that this effect is restored during the simultaneous administration of enalapril. (Hypertension. 1994;23 [suppl I]:I-225-I-230.) I amino acid infusion? (2) Is the response modified by sodium dietary restriction? and (3) Would the latter be changed by inhibition of the renin-angiotensin system? These observations could have considerable clinical implications concerning the possible effects of a high-protein diet in patients with essential hypertension. t is well known1'2 that a high protein intake produces a significant increase in both renal plasma flow (RPF) and glomerular filtration rate (GFR). These effects have been held responsible for accelerating glomerular damage, mainly in patients with preexisting renal insufficiency.3 However, it is not known if similar deleterious effects are exerted by high-protein diets in patients with essential hypertension. Intravenous administration of an amino acid combination used in parenteral nutrition therapy increases RPF and GFR4 in normotensive volunteers. In these normotensive individuals, dietary sodium restriction inhibits the renal responses to amino acid infusion; however, administration of a converting enzyme inhibitor during sodium restriction restores the vasodilator renal response.4 A similar renal response should not be assumed for patients with essential hypertension. In these patients the kidney endures higher sympathetic tone5 and higher renal vascular reactivity.6 Likewise, angiotensin II (Ang II) may contribute to the renal vasoconstriction of hypertension.7 Hence, renal vasoconstriction is a frequent if not constant finding in essential hypertension. We speculated that these pressor stimuli, seen in hypertensive but not in normotensive individuals, could restrict a protein-induced renal vasodilation. Furthermore, we felt the basis for such a notion could lie in the activity of the renin-angiotensin system. This study was designed to answer the following questions: (1) Is the kidney of patients with essential hypertension able to increase RPF and GFR in response to an From Institute) Privado de Especialidades Medicas and National University of Cordoba, Argentina (LJ., J.C.C., E.P.-A.), and the Department of Physiology, Division of Hypertension, Mayo Clinic, Rochester, Minn (J.C.R.). This manuscript from the Mayo dink: was sent to Gerald F. DiBona, Editor-in-Chief, for review by expert referees, for editorial decision, and for final disposition. Reprint requests to J.C. Romero, MD, Department of Physiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Key Words • angiotensin converting enzyme inhibitors • enalapril • diet, sodium-restricted • dietary proteins • aldosterone • renin Methods Nine patients (seven women, two men; age range, 43 to 69 years) with essential hypertension were studied. All patients had diastolic blood pressure measurements in excess of 90 mm Hg on at least three occasions and a history of hypertension for at least 12 months before the study. Secondary hypertension was excluded by a clinical medical examination, urinafysis, serum creatinine, creatinine clearance, serum electrolytes, plasma aldosterone (PA), and 24-hour urinary excretion of vanillylmandelic acid and catecholamines. Renal hypertension was excluded by rapid-sequence intravenous pyelography in all patients. In some patients, radioisotopic renogram or renal arteriography was performed to exclude renal arterial disease. All antihypertensive medications were discontinued for at least 3 weeks before the study. Patients then began an isocaloric diet containing 150 mmol sodium, 0.50 g/kg body wt proteins, and free water intake. Urine urea nitrogen was determined as Urinary Urea x 0.466. Nonprotein nitrogen excretion was calculated as 29 mg nitrogen/kg per day. Total nitrogen excretion was obtained from the sum of urine urea nitrogen and nonprotein nitrogen. The protein ingestion in grams per day was calculated as the product of total nitrogen excretion and 6.25. After giving written informed consent, the patients were admitted to the hospital, weighed, and heart rate and blood pressure measured. All patients fasted from 8 PM the night before the experiment until completion of the study on the following day. During this time water was allowed ad libitum. All the procedures and written consents were approved by the local Institutional Review Committee. Experimental Protocol At the beginning of each experiment, a urethral catheter was placed for the collection of urine, and the patients reclined in the supine position and remained in this position for the 1-226 Supplement I Hypertension Vol 23, No 1 January 1994 Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 duration of the experiment. The clearances of inulin (for determination of GFR) and /wra-aminohippurate (PAH) for calculation of RPF were measured during diuresis, which was elicited by the oral ingestion of 20 mL water/kg body wt during each clearance period. Priming boluses of inulin (50 mg/kg) and PAH (8 mg/kg) were administered (both diluted in 5% dextrose) over 5 minutes. This was followed by continuous infusions of inulin (0.5 mg/kg per minute) and PAH (0.25 mg/kg per minute) at a total constant rate of 24.66 mL/h by an infusion pump (Harvard Apparatus, South Natick, Mass). After a 45 -minute equilibration period, the bladder was emptied, and two consecutive 30-minute control clearances were obtained. Urine volume (UV) and sodium, PAH, and inulin concentrations were measured during each clearance period. Blood samples were obtained at the midpoint of each clearance period from the contralateral arm vein for measurement of plasma inulin, PAH, sodium, potassium, renin activity (PRA), and PA. The values for these two periods were averaged. After the control clearances, a 10% amino acid solution commonly used for parenteral nutrition was infused at a rate of 0.70 mL/kg per hour. The amino acid composition of this solution is shown in Table 1. Because the volume infused each minute varied between 0.72 (patient 4) and 1.07 mL (patient 1), no correction was made in the osmolality of the solution. It was assumed that such small volumes diluted in the much larger extracellular fluid volume did not change plasma osmolality. The amino acid infusion was continued for 4 hours, and urine and plasma variables were measured during the last 30 minutes of each hour. TABLE 1. Composition of the 10% Amino Acid Solution Amount, mg L-lsoleudne 720 L-Leucine 940 L-Lyslne L-glutamate 720 L-Methlonine 400 L-Phenylalanine 440 L-Threonine 520 L-Tryptophan 160 L-Valine 800 L-Arginine 980 L-Hlstidine 300 L-Alanine 1280 L-Prollne 860 Serlne 420 Tyrosine Glycine Osmolality 44 1280 lOOOmOsm/L NaiEDTA Water for Injection Baseline Studies The control studies were conducted after the patients were allowed 3 days of free sodium intake. Twenty-four-hour urinary sodium excretion (UN,V) was measured the day before the amino acid infusion. Studies During Low Sodium Diet Negative sodium balance verified by urinary sodium concentration was achieved by an oral dose of furosemide (80 mg) followed by 3 days of a 40-mmol/d sodium and 60-mmol/d potassium diet. Twenty-four-hour Un,V was measured on the third day, and on the fourth day the amino acid infusion was repeated. Studies During Low Sodium Diet and Treatment With Enalapril After the completion of the study on the low sodium diet, enalapril (10 mg) was administered orally beginning at 8 PM on that same day and every night for the next 3 days. During this period, the patients were kept on the low sodium diet (40 mmol/d). Another 24-hour UN,V was measured on the third day of enalapril administration, and the infusion study was repeated the following day. Analysis Urinary and plasma PAH and inulin were measured by a photocokjrimetric method. Urinary and plasma sodium and potassium concentrations were determined by flame photometry. PRA was measured by radioimmunoassay using a commercial kit (Gamma Coat Kit, Baxter Corp, Cambridge, Mass). PA was measured by solid-phase radioimmunoassay (Coat-A-Count, Diagnostic Products Corp, Los Angeles, Calif). Statistical Methods Data are presented as mean±SEM. The significance of the difference of the recorded values between groups was evaluated with a randomized block analysis of variance and the Newman-Keuls multiple-range test. Results Effects of Amino Acid Infusion During Normal Sodium Diet During a normal sodium diet (24-hour UN>V the day before the study averaged 126.3±11.1 mmol), the infusion of amino acids induced a progressive increase in RPF that was significant by the fourth hour (Table 2). These increments in flow from hour 1 to hour 4 averaged approximately 24% above control. Similarly, GFR progressively increased and became significantly elevated above control (22%) by the fourth hour of the amino acid infusion. Fractional excretion of sodium (Fe Nt ), total UNiV, UV, fractional excretion of potassium (FeK), PRA, and PA remained unchanged (Table 2). During the infusion, neither systolic nor diastolic blood pressure experienced any change of importance. Plasma potassium did not change and averaged from 4.1 to 4.4 mmol/L during the experiment. Amino Acid Infusion During Low Sodium Diet The procedures adopted to induce a negative balance of sodium (a single oral dose of 80 mg furosemide followed by 3 days of 40 mmol sodium per day) were effective in reducing the 24-hour UN.V to 27.4±1.8 mmol and the total UN,V to 124±16 junol/min (Table 3). GFR was significantly decreased by the low sodium diet (from 82±8 to 71±8 mL/min). However, no significant changes were observed in RPF (from 383 ±58 to 361 ±45 mlVmin). These changes were accompanied by an upward trend in PRA and PA that did not achieve statistical significance. The low sodium diet produced a significant decrease in basal values of diastolic and systolic blood pressures. The remaining parameters were not significantly affected. Juncos et al Amino Acid Effects in Essential Hypertension TABLE 2. 1-227 Effects of Amlno Acid Infusion In Hypertensive Patients Receiving a Normal Sodium Diet Measurement Control 1 Hour 2 Hours 3 Hours 4 Hours RPF, (mL/min)/1.73 m* 383±58 435±62 468±60 471 ±58 478±51* GFR, (mL/min)/1.73 m2 82±8 UV, mUmln 5±0.9 92±11 95+11 102±13 100±13* 4.7±1 4.9±1.3 4.2±1 4.1 ±0.8 208±40 166±20 UN,V, /imol/min 197±32 183±28 170±31 Few.,% 1.8±0.3 1.6±0.3 1.5±0.3 1.7±0.4 1.4±0.3 22.5±1.9 20.9±2.2 18±2.4 21.1 ±7.9 20.7±8.3 2±0.6 1.6±0.5 1.7±0.6 1.4±0.3 1.2±0.2 24.9±7 23.7±6.4 23.6±7.1 19.7±6.1 20.4±5.9 SBP, mm Hg 172±6 167±6 164±5 162±5 161±5 DBP, mm Hg 104±3 104±1 204±1 104±1 103±1 F6K,% PRA (ng Ang l/mL)/h PA, ng/dL , fractional RPF Indicates renal plasma flow; QFR, gkxnerular filtration rate; UV, urine volume; U^V, urinary sodium excretion rate; excretion of sodium; FeK, fractional excretion of potassium; PRA, plasma renln activity; Ang I, angiotensin I; PA plasma aldosterone; SBP, systolic Wood pressure; and DBP, diastolic Wood pressure. *P<.05 vs control period. Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 During dietary sodium restriction, amino acid infusion failed to alter RPF, GFR, or PRA, which remained fairly stable. In contrast, PA levels decreased to 45% of the control value by the fourth hour of the infusion. Amino acid infusion had no effect on UV, Fe Nl , or FeK. No significant changes were observed in systolic or diastolic blood pressures or in plasma potassium (4.2 to 4.4 mmol/L). Effect of Amino Acid Infusions in Patients on Low Sodium Diet Pretreated With Enalapril Patients treated with enalapril for 3 days simultaneously with the low sodium intake exhibited an average 24-hour UN,V of 34.9±7.6 mmol, which is comparable to that recorded during the low sodium diet without enalapril. However, the administration of enalapril increased control values of GFR (88 ±9 mL/min, Table 4) 24% above the control value obtained in the same patients during sodium-restricted diets without enalapril (71 ±8 mL/min, Table 3). However, these values were not significantly higher than those recorded during the control period of a normal sodium intake. Enalapril did not alter basal values of RPF (388 ±35 versus 361 ±45 mL/min), UN.V, UV, FeNa, or FeK. Similarly, enalapril produced a significant threefold increase in the control values of PRA, whereas control PA was decreased 50%. However, plasma potassium remained unaltered from 4.4 to 4.1 mmol/L. Enalapril also decreased the control values of systolic blood pressure by 16% (153±4 versus 129±6 mm Hg) without altering the control values of diastolic blood pressure. During enalapril treatment, the suppressor effects of a low sodium diet on amino acid-induced increments in RPF and GFR were reversed. In fact, as shown in Table 4, RPF and GFR were significantly above the control level, reaching values comparable to those seen during amino acid infusion on a normal sodium diet. The mean rise in RPF at 4 hours was 38.4%, well above the 17.0% rise in GFR. This is reflected in a mean 3.5% fall in filtration fraction. Discussion Changes in Renal Hemodynamics This study included nine randomly selected patients with essential hypertension who exhibited a wide dis- persion in RPF and GFR values that ranged from subnormal to normal levels. This finding most probably reflects the variable renal damage inflicted by variable periods of hypertensive disease. However, the relatively low basal values of hemodynamic parameters also could have been produced by dietary protein restriction imposed 3 days before the study. 810 We performed this maneuver to standardize the renal response to amino acid infusions. Within these experimental conditions, our study demonstrated that amino acid infusions induced increases in RPF and GFR that were inhibited by sodium restriction. The administration of enalapril during the sodium restriction restored the effects of amino acid infusion on RPF and GFR. These results, although analogous to those reported in healthy individuals, were not expected. Patients with essential hypertension have different basal renal hemodynamics, and they are under the influence of distinct pressor effects. Thus, we expected to see resistance to the vasodilator effects of amino acids. This was not so and shows that patients with essential hypertension are exposed to protein-induced hyperfiltration. The mechanisms responsible for these effects are difficult to identify because the intimate mode of action underlying the vasodilator effects of amino acids are poorly understood. Early hypotheses on the participation of pituitary growth hormone,11 as well as liver hormones such as glomerulopressin,12 were ruled out after amino acids were shown to produce significant increases in renal hemodynamics in patients with panhypopituitarism13 and in animals in whom the liver was functionally excluded from the general circulation.14 Similarly, the participation of glucagon315 was eliminated mainly because the infusion of this hormone failed to increase renal hemodynamics.16 More recently, the renal response to amino acid infusion has been regarded as a manifestation of endothelial modulatory function. Benigni et al17 have shown that hyperfiltration induced by a high protein intake in animals with experimental nephrosis was related to a significant increase in 6-ketoprostaglandin F l o and suppressed by indomethacin, suggesting that prostacyclin plays a role in the hyperfiltration response to amino acid infusion. Ruilope et al4 reported that in normotensive 1-228 Supplement I Hypertension Vol 23, No 1 January 1994 TABLE 3. Effects of Amlno Acid Infusion In Hypertensive Patients on a Low Sodium Diet Control 1 Hour 2 Hours 3 Hours 4 Hours 361 ±45 372±46 388±42 384±54 411 ±51 71 ±8 71 ±9 73±6 72±8 77±7 4±0.8 3.8±0.7 3.9±0.8 3.1 ±0.7 3.8±0.6 124±16 124±16 140±20 136±17 203±53 1.5±0.3 1.4±0.3 1.6±0.3 1.5±0.2 2±0.5 23.6±3.5 21.4±3.3 21.4±3.6 19.1 ±3.3 18.9±2.8 3.2±0.5 3.5±0.7 3.7±0.8 2.8±0.7 3.1 ±0.7 37.3±8.7 31.5±8.3 25.5±7.6 21.6±3.8 20.2±5* SBP, mm Hg 153±4 151 ±5 151±5 151±5 151 ±5 DBP, mm Hg 88±4 87±4 86±4 85±4 85±4 (Measurement RPF, (mL/min)/1.73 m GFR, 2 (m\Jm\n)r\.73rtf UV, mL/min UNJV, fimol/min FON.,% FOK, % PRA, (ng Ang l/mL)/h PA, ng/dL RPF Indicates renal plasma flow; GFR, glomerular filtration rate; UV, urine volume; UM.V, urinary sodium excretion rate; Few,, fractional exaetion of sodium; Fox, fractional excretion of potassium; PRA, plasma renin activity; Ang I, angiotensin I; PA, plasma aldosterone; SBP, systolic blood pressure; and DBP, dlastolic blood pressure. *P<.05 vs control period. Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 patients pretreated with indomethacin, the renal response to amino acid infusion was inhibited. Endothelium-derived relaxing factor, namely, nitric oxide (NO), which is known to be produced from the nitrogen atom contained in the JV-guanidino group of L-arginine,18 also has been implicated in the amino acid response. In rats, amino acid-induced increments in RPF or GFR are largely prevented by prior administration of an NO inhibitor, 7V°-monomethyl L-arginine.1921 This observation is in agreement with the study of Premen and Dobbins,22 who have shown that amino acid combinations of L- but not r>isomers elevated RPF and GFR, and with Castellino et al,23 who demonstrated that RPF and GFR were increased by a solution of gluconeogenic amino acids containing L-arginine. NO may have taken part in the renal hemodynamic response to amino acids in our patients during a normal salt diet. The suppressed response after sodium restriction could have been caused by depressed NO activity. This notion is supported by the work of Shultz and Tolins24 showing that NO activity rises during a high salt intake, thus suggesting a role of NO in renal adaptation to variations in sodium intake. An alternative mechanism proposed by Woods et al25 and DeNicola et al21 is that amino acids induce an afferent arteriole vasodilatation through a tubular glomerular feedback mechanism. However, our results do not allow a distinction among these possibilities. The involvement of Ang II in the renal response to amino acid infusion is strongly advocated by the suppressive effect of sodium dietary restriction and the restoring action of enalapril. These results are comparable to those reported by Ruilope et al4 in normotensive patients. Moreover, Slomowitz et al26 observed that captopril enhanced the renal response to amino acids in normotensive diabetics. Although these patients were on a normal sodium diet, the results were attributed to the abnormally elevated Ang II levels in this disease.26 The specific mechanism through which changes in the formation of Ang II could influence the responses to amino acid remains unknown. Some investigators have suggested that Ang II could alter the sensitivity of tubular glomerular feedback responses.27 However, others have considered that the intrarenal changes in the TABLE 4. Effects of Amlno Acid Infusion In Hypertensive Patients on a Low Sodium Diet and During the Inhibition of Converting Enzyme Measurement RPF, (mL/mlnyi.TSm 2 GFR, (ml_/min)/1.73 m2 Control 1 Hour 2 Hours 3 Hours 4 Hours 388±35 450±38 467±44 518±53 537±48* 88±9 100±11 99±9 103±10 103±10* 4±0.7 UV, mL/min 3.8±0.8 4.1 ±0.7 3.8±0.7 UM,V, junol/min 144±24 148±20 1.1 ±0.2 157±29 1.2±0.2 168±25 15.2±2.5 15.2±2.5 12.3±2.1 FON.,% 1.3±0.3 154±20 1.2±0.2 FOK.% 18.3±2.2 16.2±1.8 3.3±0.4 1.3±0.2 9.9±3.3 8±3.4 7.5±3.4 6.6±2.9 6.2±3.5 PA, ng/dL 18.8±2.1 16.6±8.3 15.1 ±3.6 14.4±2.5 13.6±3.7 SBP, mm Hg 129±6 126±6 126±6 126±6 126±6 DBP, mm Hg 79±5 80±5 79±5 77±5 77±5 PRA, (ng Ang l/mL)/h RPF indicates renal plasma flow; GFR, glomerular filtration rate; UV, urine volume; UMV, urinary sodium excretion rate; Fa*,, fractional excretion of sodium; FBK, fractional excretion of potassium; PRA, plasma renin activity; Ang I, angiotensin I; PA, plasma aldosterone; SBP, systolic blood pressure; and DBP, diastolic blood pressure. *P<.05 vs control period. Juncos et al Amino Acid Effects in Essential Hypertension Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 formation of Ang II involve reciprocal alterations in the synthesis of NO in a manner such that the inhibition of Ang II formation28 or blockade of Ang II receptors29 favors the expression of the effects of NO stimulation. Recently, DeNicola et al21 showed that pretreatment with the Ang II receptor antagonist DuP 753 restores the glomemlar and tubular response to glycine during NO inhibition, suggesting that NO is a physiological antagonist of Ang II. These findings support our results after angiotensin converting enzyme inhibition. It could therefore be assumed that much of the renal effect produced by the amino acid-mediated stimulation of NO was curtailed by the presence of Ang II. The amino acid infusion during angiotensin converting enzyme inhibition caused a percent rise in RPF twice as large as that of GFR. Thus, filtration fraction decreased substantially (3.5%). This predominant effect on RPF could only indicate a significant reduction in efferent arteriolar resistance. In other words, blood flow through an amino acid-dilated afferent arteriole encounters little resistance through the also dilated efferent arteriole. Other reported effects of angiotensin converting enzyme inhibition on renal hemodynamics, such as increased K, or afferent vasodilation, could not explain the drop in filtration fraction during amino acid infusion. It should be mentioned that the average increments in GFR and RPF during amino acid infusion with a normal sodium diet are within the range reported by other investigators in a normotensive population.8'26-30-31 Changes in Excretory Function, Plasma Renin Activity, and Plasma Aldosterone As reported by others,32 the amino acid infusions induced a downward trend in PRA during a normal sodium diet as well as during dietary sodium restriction with the concomitant administration of a converting enzyme inhibitor that could be attributed to a stimulation of endothelium-derived relaxing factor.3335 However, this issue deserves further investigation. Similarly, the administration of amino acids produces a consistent fall in PA values during a low sodium diet that appears to be independent of fluctuations in PRA. These decrements in PA also occurred in the absence of any significant changes in plasma potassium concentration. The mechanism by which amino acids influence aldosterone secretion is uncertain. The observations of this study have important clinical implications because they indicate that (1) in untreated essential hypertensive patients, an increase in circulating amino acids is capable of exposing the glomeruli to the same degree of hyperfiltration as that shown by other investigators to accelerate glomemlar damage9-36; (2) such a deleterious effect of amino acids on glomerular function is likely to be ameliorated by negative sodium balance, a condition routinely obtained by sodium dietary restriction and/or the administration of diuretics in patients with essential hypertension; and (3) the protective effects of sodium restriction on glomerular hyperfiltration rate appear to be reversed by the administration of enalapril. However, because of the observed fall in filtration fraction, the clinical significance of these acute effects of amino acids should be carefully evaluated to understand the more prolonged 1-229 beneficial effects that have been reported during longterm treatment with converting enzyme inhibitor.31 Acknowledgments This study was supported by grant HL-16496 from the National Institutes of Health and by grants from the Mayo Foundation. We thank Sandra Baigorria for her excellent technical assistance. References 1. Pullman TN, Ahing AS, Dern RJ, Landowne M. The influence of dietary protein intake on specific renaJ functions in normal man. JLabCUnMed. 1954;44:320-332. 2. O'Connor WJ, Summerill RA. The effect of a meal of meat on glomerular filtration rate in dogs at normal urine flows. J Physiol {Land). 1976^56:81-91. 3. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of the kidney disease: the role of hemodynamicalry mediated glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 1982;307: 652-659. 4. Ruilope L, Rodicio J, Garcia Robles R, Sancho J, Miranda B, Granger JP, Romero J C Influence of a low sodium diet on the renal response to amino acid infusions in humans. Kidney InL 1987;31:992-999. 5. DiBona GF. Sympathetic neural control of the kidney in hypertension. Hypertension. 1992;19(suppl I):I-28-I-35. 6. Collins MG, DeMay C, Vanhoutte PM. Renal vascular reactivity in the young spontaneously hypertensive rat. Hypertension. 1980;2: 45-52. 7. Arcndshorst WJ, Chatziantoniou C, Daniels FH. Role of angiotensin in the renal vasoconstriction observed during the development of genetic hypertension. Kidney Int. 1990;38(suppl): S92-S96. 8. Bosch JP, Saccaggi A, Lauer A, Ronco C, Belledonc M, Glabman S. Renal functional reserve in humans: effect of protein intake on glomerular filtration rate. Am J Med. 1983;75:943-950. 9. Hostetter TH, Meyer TW, Rennke HG, Brenner BM. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney InL 1986;30:509-517. 10. Castellino P, DeFronzo RA. Effect of plasma amino acid and hormone concentrations on renal plasma flow and glomerular filtration rate. Blood Purif. 1988;6:240-249. 11. Meyer TW, Troy JL, Rennke HG, Brenner BM. Pituitary ablation preserves glomerular structure and function in rats with renal ablation. In: Proceedings of the 9th International Congress of Nephrology, June 11-16, 1984; Los Angeles, Calif; 355. Abstract. 12. Alvestrand A, Bergstrom J. Glomerular hyperfiltration after protein ingestion, during glucagon infusion and in insulindependent diabetes is induced by a liver hormone: deficient production of this hormone in hepatic failure causes hepatorenal syndrome. Lancet 1984;1:195-197. 13. 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Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 Renal response to amino acid infusion in essential hypertension. L Juncos, J C Cornejo, E Pamies-Andreu and J C Romero Hypertension. 1994;23:I225 doi: 10.1161/01.HYP.23.1_Suppl.I225 Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017 Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1994 American Heart Association, Inc. All rights reserved. Print ISSN: 0194-911X. Online ISSN: 1524-4563 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/23/1_Suppl/I225 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. 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