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R Loutzenhiser

Publications and source records attributed to R Loutzenhiser.

62 records · Page 4Linked to original sources

Metabolism of arginine by the isolated perfused rat kidney.

In order to evaluate the renal contribution to the metabolism of arginine, we have evaluated its biosynthesis and catabolism in the isolated perfused rat kidney. The kidneys of eight male Sprague-Dawley rats were perfused with Krebs-Ringer-bicarbonate buffer containing albumin and amino acids. Twenty-five muCi of L-[guanidino-14C]arginine or 25 muCi L-[guanidino-14C]citrulline were added to the system and radiochromatograms of the perfusate were obtained at 0, 30, 60, and 90 min. Perfusate levels of urea, creatine, and guanidine derivatives were measured with high-pressure liquid chromatography. During perfusion there was net utilization of arginine and net production of creatine, guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA). The guanidino carbon of arginine was incorporated by the kidney into urea, creatine GSA, GAA, and guanidinobutyric acid. The production of 14C-labeled urea from L-[guanidino-14C]citrulline was substantially lower than that previously demonstrated in the liver, while that of arginine was approximately 20 times greater. These studies demonstrate the important contribution of the kidney to the synthesis and metabolism of arginine.

Acetates↗

Volume as a determinant of plasma aldosterone in anephric man.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI), produces a prompt and profound suppression of plasma renin activity (PRA) and plasma aldosterone concentration (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was utilized to assess the responsiveness of PA to volume expansion in 12 anephric subjects. The patients were studied on 2 occasions, 48 h after their last dialysis: during a seated control study (7 of the patients) and during 3 h of NI (all 12 patients). The conditions of seated posture and time of day were identical. Blood for PRA, PA, and cortisol was obtained at 30-min intervals for 5 h. PRA was undetectable in all patients. NI failed to alter PA. Plasma cortisol declined progressively throughout NI; serum potassium concentration remained unchanged. An identical NI study in normal subjects suppressed PA by 60%. These data demonstrate that when plasma composition and posture are maintained constant, marked central hypervolemia does not alter PA in anephric man. The present findings support the role of the renin-angiotensin system as the prepotent mediator of volume-induced changes in PA.

Adult↗

Effects of water immersion on renal hemodynamics in normal man.

Although previous studies have demonstrated that water immersion to the neck (NI) results in a significant natriuresis and diuresis, the mechanisms are incompletely delineated. Since recent studies have demonstrated that NI induces a marked increase in cardiac index, it is possible that, as a consequence, renal hemodynamics may be augmented markedly during NI thereby mediating the encountered renal changes. The present study was undertaken to delineate the effects of NI on renal plasma flow and glomerular filtration rate as assessed by the clearance of PAH (CPAH) and inulin (CIn), respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter CIn or CPAH at a time when sodium excretion was increasing markedly. The constancy of CPAH during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a naturiuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

Adult↗

Failure of water immersion to influence parathyroid hormone secretion and renal phosphate handling in normal man.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis which is quantitatively identical to that induced by the acute administration of 2 L. of saline. Since the central hypervolemia induced by NI occurs without concomitant alterations in serum ionized calcium concentration (Ca++), the NI model was utilized to assess the role of volume in the regulation of PTH secretion in man. Seven normal subjects were studied following 11 hours of dehydration on two occasions, control and NI. The conditions of seated posture and time of day were identical. Blood for ionized calcium and PTH was obtained at 30-minute intervals for 6 hours. NI resulted in a significant increase in UNaV from a prestudy value of 78 +/- 12 (S.E.M.) to 222 +/- 20 muEq per minute (p less than 0.001). Concomitantly, Ca++ remained constant, ranging between 4.57 to 4.71 mg. per cent. Despite the volume-induced natriuresis, PTH was not altered throughout 5 hours of NI, ranging from 36 +/- 7 to 45 +/- 5 mul-Eq. per milliliter. Phosphate excretion remained constant. These data indicate that central volume expansion does not alter PTH in normal man when the variables of ionized calcium, posture, and time of day are controlled. Furthermore, the current demonstration of the absence of phosphaturia during immersion despite the probability that the distal delivery of phosphate was enhanced, permits consideration of the possibility that the concept of a distal tubular reabsorptive site for phosphate may be applicable to man.

Adult↗

PN 200-110, a new calcium antagonist: electrophysiological, inotropic, and chronotropic effects on guinea pig myocardial tissue and effects on contraction and calcium uptake of rabbit aorta.

The compound isopropyl 4-(2,1,3- benzoxadiazol -4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyrid inecarboxylate (code name PN 200-110 [PN]) was investigated for calcium antagonistic effects in experiments in vitro. Action potentials recorded with intracellular microelectrodes in guinea pig papillary muscles were changed little by PN, 10(-7) M, except for a slight shortening of the duration of the plateau phase. Slow action potentials elicited in partially depolarized papillary muscles were gradually diminished and finally blocked by this concentration of PN. Contractile force was diminished in normal and partially depolarized muscles. The rate of spontaneously beating guinea pig right atria was decreased dose dependently, and the EC25 was 4.5 x 10(-10) M. The EC25 for the negative inotropic effects measured on paced guinea pig left atria was 1.5 x 10(-8) M. No membrane-stabilizing effects were found. Calcium-induced contraction of rabbit aorta in depolarizing bath solution was inhibited with an apparent pA2 of 10.3. Contraction elicited by graded depolarization at a constant calcium concentration was inhibited with an EC50 of 1.4 x 10(-9) M. Under resting conditions PN did not alter net uptake of 45Ca2+. KCl-stimulated uptake was inhibited with an EC50 of 3.6 x 10(-9) M. Neither noradrenaline-induced contractions nor noradrenaline-stimulated net uptake of 45Ca2+ were inhibited by a concentration of PN as high as 10(-5) M. PN thus is selective on cardiac tissue with respect to negative chronotropic versus inotropic activity and on rabbit aorta with respect to potential-operated versus receptor-operated channels.

Action Potentials↗