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J R Ingelfinger

Publications and source records attributed to J R Ingelfinger.

At least 73 records · Page 4Linked to original sources
PubMed1989

Atrial natriuretic factor-specific antibody as a tool for physiological studies. Evidence for role of atrial natriuretic factor in aldosterone and renal electrolyte regulation.

Numerous studies have shown that administration of atrial natriuretic factor (ANF) increases urinary sodium excretion and urine flow, decreases blood pressure, and inhibits renin and aldosterone release. However, the role of endogenous ANF in the regulation of renal sodium excretion, blood pressure, plasma renin activity, and aldosterone level remains to be elucidated. To examine this issue, endogenous ANF was blocked by administering rat ANF-(99-126) specific antiserum (Ab) to anesthetized rats (n = 7). Control animals received either no injection (time controls, n = 10) or preimmune serum (n = 8). Blockade of endogenous ANF caused a 28 +/- 0.09%, 47 +/- 0.08%, and 51 +/- 0.08% fall in sodium excretion at 15, 30, and 45 minutes after Ab injection (p less than 0.05, p less than 0.01, p less than 0.01, respectively). Urine flow fell 35 +/- 7% at 45 minutes after ANF inhibition (p less than 0.05). Plasma ANF levels were suppressed to undetectable levels. However, there were no changes in blood pressure throughout the experiment nor plasma renin concentration when measured at 45 minutes after Ab injection. Interestingly, plasma aldosterone concentration increased significantly (by approximately 50%, p less than 0.025), in response to Ab. Completeness of blockade was demonstrated by the absence of sodium excretion response to exogenous ANF (500 ng). In either the time control or the preimmune serum group, urinary excretion, blood pressure, plasma ANF, plasma renin concentration, and plasma aldosterone concentration were unchanged throughout the experiment. In contrast to the Ab group, a challenge with exogenous ANF (500 ng) increased sodium excretion by 2.17 mueq/min in the preimmune serum group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1989

Androgen regulation of rat renal angiotensinogen messenger RNA expression.

Renal angiotensinogen (ang-n) mRNA concentration in the male WKY rat increases significantly during puberty. Furthermore, renal angiotensinogen mRNA level in the adult female WKY rat is considerably lower than in the male. The present study investigates the role of androgen in differential renal ang-n mRNA expression. Northern and slot blot analyses with alpha-32P labeled ang-n cDNA (pRang 3) demonstrated that castration lowered ang-n mRNA levels in the male kidney by greater than or equal to 60% compared with control, suggesting that androgen may be involved with renal ang-n gene regulation. Moreover, male WKY rats castrated as weanlings and normal adult female WKY rats each implanted with testosterone displayed significant (P less than 0.05) increases in renal ang-n mRNA levels. Our observations, taken together with previous reports that androgen influences proximal tubule morphology and the tubular expression of transport proteins (e.g., Na+/H+ antiporter), may have important physiological implications for understanding the relationship between androgen and angiotensin in the regulation of tubular function.

Aging↗
PubMed1989

Processing of one-chain to two-chain renin in the mouse submandibular gland is influenced by androgen.

In the male CD-1 mouse submandibular gland (SMG) renin activity increases markedly with puberty. We have reported that this is, in part, due to an androgen-mediated increase in renin gene transcription. In this study, we examined whether posttranslational processing is also influenced by androgen. We studied secretion and processing of active renin in the CD-1 male mouse SMG which secretes primarily the Ren-2 renin isozyme before and after puberty and also compared findings with the adult female CD-1 mouse. Maturation increases renin level and secretion rate in the male SMG but much less in the female. In addition, Western blot analysis of molecular forms of renin in SMG tissue and media shows a predominance of 1-chain intermediate form of renin before puberty but of the 2-chain mature form thereafter. Adult female SMG contains and secretes much less active renin than the male organ. Administration of testosterone to the female CD-1 mouse induces an adult male level and pattern of secretion, with high concentrations of active 2-chain renin being secreted. These data suggest that SMG renin is androgen regulated, in part by an androgen-responsive enzyme that processes 1-chain renin to the 2-chain form.

Aging↗
PubMed1988

Regulation of extra-renal renin during ontogeny.

Previous studies demonstrated that the level of renin in the male submandibular gland (SMG) of mouse strains that contain renin genes [e.g. Cr1:CD-1(1CR)BR] increased dramatically at puberty, but a less pronounced response was seen in the C57BL/10J (a strain that has a single renin gene). However, the expression of renin in kidney and other extrarenal tissues throughout growth and development has not been examined. In this study we characterized developmental changes in renal renin and certain extrarenal renin levels in the male and female CD-1 mouse and male C-57 mouse. Renal renin activity remains relatively constant throughout ontogeny in male and female CD-1 mice and in the C-57 male mouse. In the CD-1 male mouse, SMG renin levels vary during ontogeny, coincident with periods in growth and development that are associated with hormonal shifts. Glandular renin levels are higher in the neonatal period than at 2-3 weeks of age, and then rise dramatically with the onset of puberty. Renin levels in the adrenal and testis of the CD-1 male mouse follow a similar temporal pattern. However, this dramatic increase in gonadal, adrenal, and SMG renin in the CD-1 male mouse at puberty is not seen in the organs from the CD-1 female mouse or those of the C-57 male mouse. Taken together, the present results demonstrated that the expression of extrarenal sources of renin is under genetic and hormonal influences. In addition, our data suggest that control of extrarenal renin expression may differ from that of renal renin.

Adrenal Glands↗
PubMed1987

Left ventricular mechanics and contractile state in children and young adults with end-stage renal disease: effect of dialysis and renal transplantation.

The potential existence of a specific uremia-associated myocardial depressant factor was explored by evaluating nine pediatric subjects (3 to 21 years) without evidence of coronary artery disease or long-standing hypertension 1) before entering a dialysis program, 2) while undergoing a long-term dialysis regimen, and 3) after successful renal transplantation. Myocardial contractility was quantitated with load-independent indexes using the end-systolic pressure-dimension relation (Emax) and the relation of rate-corrected velocity of shortening to end-systolic wall stress. Myocardial loading status was determined by the direct measurement of afterload (end-systolic wall stress) and the functional quantitation of preload (differences between the relation of fractional shortening and velocity of shortening to end-systolic stress). Most patients (55%) were found to have abnormal ejection phase indexes of ventricular function either before or after entry into dialysis. However, contractility was normal in all subjects at each of their evaluations, and no change in contractility was found after dialysis or transplantation. Loading status was highly variable and usually abnormal before transplantation and accounted entirely for the abnormalities of fractional shortening and velocity of shortening. Transplantation invariably resulted in normalization of loading status and ejection phase indexes of ventricular function. In these children and young adults with uremia, abnormal ejection phase indexes of ventricular function were frequent and caused by associated abnormalities in ventricular loading. Contractility, however, was normal and no evidence of a uremia-associated myocardial depressant was found.

Adolescent↗
PubMed1987

Tissue-specific regulation of renin expression in the mouse.

Increasing biochemical evidence suggests that the renin-angiotensin system may be present in may extrarenal tissues. We have employed the mouse submandibular gland renin complementary DNA (pDD-1D2) and the rat liver angiotensinogen complementary DNA (pRang 3) to demonstrate that renin and angiotensinogen messenger RNAs are expressed in the mouse kidney, submandibular gland, heart, adrenal, brain, and testis. To elucidate the factors that influence local tissue renin-angiotensin expressions, we studied tissue renin messenger RNA and enzymatic levels of male mice in response to sodium depletion and castration. Sodium depletion resulted in increased renin expression in the kidney, heart, and adrenal, but not in the submandibular gland and testis. Castration lowered renin levels in all extrarenal tissues but appeared to increase renin level in the kidney. Taken together, the above data demonstrate tissue-specific regulation of renin expression and imply different functions for the sodium responsive and nonresponsive systems.

Adrenal Glands↗
PubMed1986

Regulation of tissue renin and angiotensin gene expressions.

Recent studies employing molecular biological techniques demonstrate that renin and angiotensinogen genes are expressed in various tissues. We have observed tissue-specific regulation of renin and angiotensinogen gene expressions. Renin expression in kidney, heart, and adrenal are stimulated by sodium depletion and beta-adrenergic agonist. Submandibular gland and genital renins are not. Instead, the renin expression in these tissues are influenced by androgen and/or hormones that are activated during ontogeny. Genetic influence of tissue renin expression also exists, i.e., the submandibular gland, cardiac, and testicular renin activities are higher in the two gene strains, whereas kidney renin activity does not differ between different strains. Tissue-specific regulation of angiotensinogen mRNA is also observed when rats are placed on a low-sodium diet. Sodium depletion stimulates renin angiotensinogen mRNA expression but does not influence hepatic angiotensinogen mRNA levels. Tissue-specific regulation of renin angiotensin may have important functional implications. Increased local production of angiotensin should influence tissue angiotensin-mediated responses that may be independent of the circulating system.

Angiotensinogen↗
PubMed1986

Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla.

Rat liver angiotensinogen cDNA (pRang 3) and mouse renin cDNA (pDD-1D2) were used to identify angiotensinogen and renin mRNA sequences in rat kidney cortex and medulla in rats on high and low salt diet. Angiotensinogen mRNA sequences were present in renal cortex and medulla in apparently equal proportions, whereas renin mRNA sequences were found primarily in renal cortex. Average relative signal of rat liver to whole kidney angiotensinogen mRNA was 100:3. Densitometric analysis of Northern blots demonstrated that renal cortical angiotensinogen mRNA concentrations increased 3.5-fold (P less than 0.001) and medulla, 1.5-fold (P less than 0.005) on low sodium compared with high sodium diet, whereas renal cortex renin mRNA levels increased 6.8-fold (P less than 0.0005). Dietary sodium did not significantly influence liver angiotensinogen mRNA levels. These findings provide evidence for sodium regulation of renal renin and angiotensinogen mRNA expressions, which supports potential existence of an intrarenally regulated RAS and suggest that different factors regulate renal and hepatic angiotensinogen.

Angiotensinogen↗
PubMed1986

Multiple sites of regulation of mouse renin expression in ontogeny.

How local renin expression is regulated in many tissues has yet to be defined. In the present studies the ontogeny of renin in submandibular gland (SMG) and kidney of CD-1 mice was examined in order to determine whether renal and extrarenal renin are similarly expressed. In males, submandibular gland (SMG) renin and renin secretory rate increase at puberty as androgen rises. The ratio of secreted forms (1-chain renin cf. 2-chain) seen on Western blots shows predominance of 1-chain prior to puberty and 2-chain thereafter. This androgen influence on renin processing and secretion was supported by reversion to prepubertal patterns with castration of adult males and by conversion to male pattern in androgen treated females which otherwise have low renin levels. In contrast, renal renin remains unchanged throughout development. The influence of ontogeny on renal and SMG renin mRNA was examined by Northern analysis using renin cDNA: SMG renin mRNA increases from near zero to high levels at puberty while renal renin mRNA level is high throughout. Taken together, these data suggest that SMG renin is influenced by androgens, whereas renal renin is not. Apparent differences in tissue renin regulation may have important implications for local function of this enzyme.

Adrenal Glands↗
PubMed1983

Single-dose amoxicillin therapy of uncomplicated pediatric urinary tract infections.

Forty-nine ambulatory children between 2-1/2 and 12 years of age with acute, clinically uncomplicated urinary tract infections caused by susceptible organisms were randomized to receive a single dose of amoxicillin based on weight or a 10-day course of amoxicillin therapy (conventional therapy). Patients receiving single doses of amoxicillin had a cure rate of 63%, which compares unfavorably with the cure rate of 92% in patients given conventional therapy. A failure of single-dose therapy predicted underlying radiologic abnormalities with a sensitivity of 60% and a specificity of 58%, making it a poor screening test for detecting those patients at risk for renal parenchymal damage. The antibody-coated bacteria assay had no predictive value in separating upper and lower tract disease, although it may predict underlying radiologic abnormalities. The data indicate that the response to single-dose amoxicillin therapy fails to separate upper from lower tract disease reliably and has a limited role in predicting response to conventional antimicrobial therapy.

Acute Disease↗
PubMed1983

Hemolytic uremic syndrome and crescentic glomerulonephritis complicating childhood nephrosis.

Three children with nephrotic syndrome and focal segmental glomerulosclerosis and/or mesangial proliferation on renal biopsy developed the sudden onset of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Two of the three children developed crescentic glomerulonephritis and never regained renal function while the third showed no change from his original histologic pattern and also developed chronic renal failure. These cases suggest an association between the lipoid nephrosis-focal segmental glomerulosclerosis group of glomerular diseases and crescentic glomerulonephritis, and may represent an unusual pathway in the evolution of childhood nephrosis.

Child↗
PubMed1982

Peritonitis in childhood nephrotic syndrome: 1970-1980.

A retrospective review (1970 through 1980) of 351 children with idiopathic nephrotic syndrome disclosed 24 episodes of peritonitis in 19 patients. Twenty-six percent of the patients had more than one episode. Streptococcus pneumoniae was the most common agent (50%), but Escherichia coli remained important (25%). Four cases (16%) were culture-negative. Signs of peritoneal irritation were present in all patients, including the 16 children receiving corticosteroid therapy. No morphological subtype of nephrotic syndrome could be demonstrated to be at increased risk for the development of peritonitis. Significantly decreased IgG levels and an apparent susceptibility to pneumococcal infection among blacks may be important risk factors.

Adolescent↗
PubMed1982

Comparison of cell-mediated lympholysis and mixed lymphocyte culture in the immunologic evaluation for renal transplantation.

We investigated the relationship between both pre-transplant cell-mediated lympholysis assay (CML) and mixed lymphocyte culture (MLC) and transplant outcome (graft function and survival) in 33 living, related donor renal transplants performed during the past 5 yr. Both assays were excellent predictors of transplant outcome. A positive CML assay was correlated with the occurrence of early acute rejection episodes (p less than 0.005), shortened time to graft dysfunction (serum creatinine greater than 1.5 mg/dl) (p less than 0.001), and poor long-term graft survival (p = 0.07). Similarly, a positive MLC was correlated with acute rejection episodes (p less than 0.005), graft dysfunction (p = 0.001), and poor graft survival (p less than 0.01). To determine the relative prognostic significance of the CML and MLC assays, we compared the correlation of each of them with the occurrence of acute rejection episodes. Under a logistic model of probability, the CML and MLC assays were equally predictive of an early acute rejection episode (p less than 0.01); however, the combination of CML and MLC together improved the accuracy of the prediction of an acute rejection episode by 50%. These results indicate that the CML and MLC assays are independent predictors of transplant outcome and that both tests should be an integral part of the immunologic evaluation of prospective living, related donors for renal transplantation.

Adolescent↗