Search PubMed⌕ Search

Biomedical subjects

B M Brenner

Publications and source records attributed to B M Brenner.

At least 289 records · Page 16Linked to original sources
PubMed1978

The renal circulations.

The plural is used advisedly. Each of several microcirculations with specialized structural and functional properties is necessary to the physiologic functioning of the kidney. Newly elucidated aspects of renal vascular anatomy are mapped out and clearly related to the exchange processes that occur at the capillary level in each part of the nephron to produce the final ureteral urine of the required volume and composition.

Absorption↗
PubMed1978

Mechanism of the glucocorticoid-induced increase in glomerular filtration rate.

In order to investigate the mechanism(s) by which glucocorticoids increase GFR the determinants of glomerular ultrafiltration were measured in two groups of seven Munich-Wistar rats. Group 1 rats were normal controls and group 2 rats were pretreated with methylprednisolone (MP), 15 mg/kg per day for 4 days prior to study. In rats given MP mean values for SNGFR were about 25% higher than in the control group, averaging 33.6 +/- 1.6 (SE) vs. 27.0 +/- 1.0 nl/min. Mean values for initial glomerular plasma flow rate (QA) were also about 25% higher in MP-treated rats, averaging 83.4 +/- 3.9 vs. 65.9 +/- 1.9 nl/min in controls. Mean values of the transglomerular hydraulic pressure difference (deltaP) as well as afferent (IIA) and efferent (IIE) oncotic pressures were essentially similar between control and MP-treated rats. Filtration pressure equilibrium, i.e., equality between IIE and deltaP, obtained in both groups and the mean minimum estimates of the ultrafiltration coefficient (Kf) were also similar between control and MP-treated rats. Thus, the rise in SNGFR following MP is entirely due to the increase in AQ, rather than to changes in the other determinants of ultrafiltration.

Animals↗
PubMed1978

Influence of parathyroid hormone on glomerular ultrafiltration in the rat.

Experiments were performed on 22 plasma-expanded Munich-Wistar rats to investigated the effects of parathyroid hormone (PTH) on the determinants of glomerular ultrafiltration. Mean values for single nephron filtration rate (SNGFR), glomerular plasma flow rate (QA), systemic oncotic pressure, and transglomerular hydraulic pressure difference (deltaP) were similar in acutely thyroparathyroidectomized (TPTX) rats and non-TPTX rats. Nevertheless, the glomerular capillary ultrafiltration coefficient (Kf) was uniformly higher in TPTX rats (greater than 0.113 +/- 0.005 (SE) nl/(s.mmHg)] than in non-TPTX controls (0.088 +/- 0.005). In TPTX rats, infusion of a submaximal dose (1 U/kg per min) of PTH resulted in significant decreases in SNGFR at constant QA and deltaP, due primarily to return of Kf to non-TPTX levels. Infusion of 10 U/kg per min of PTH to non-TPTX rats further reduced Kf, on average to 0.042 +/- 0.001 nl/(s.mmHg), leading to further reduction in SNGFR, whereas QA and deltaP again remained constant. These findings suggest that PTH may play an important role in modulating Kf, and consequently, SNGFR.

Animals↗
PubMed1978

Glomerular permselectivity: barrier function based on discrimination of molecular size and charge.

The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.

Animals↗
PubMed1978

Modulation by prostaglandin synthesis inhibitors of the action of exogenous angiotensin II on glomerular ultrafiltration in the rat.

We studied the effects of angiotensin II (A II) infusion, with and without inhibition of prostaglandin (PG) synthesis, on the determinants of glomerular ultrafiltration in 27 plasma volume-expanded Munich-Wistar rats. The effects of PG inhibition alone and infusion of vehicle alone also were investigated. With a pressor dose of A II single nephron (SN) GFR and total GFR did not change significantly, despite declines in both glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf), due to an offsetting rise in the transcapillary hydraulic pressure difference (deltaP). Afferent and efferent arteriolar resistances (RA and RE) increased by approximately 100% above control during A II infusion. Inhibition of PG synthesis alone and infusion of vehicle alone similarly failed to affect SNGFR and total GFR, and only slight changes occurred in the determinants of glomerular ultrafiltration in these rats. When A II infusion was accompanied by inhibition of PG synthesis, however, profound declines in SNGFR and total GFR were seen, due to further reductions in QA and 2-fold greater increases in RA and RE than occurred with the same dose of A II alone. The A II-induced fall in Kf was not affected by simultaneous PG inhibition. Thus, endogenous PGs attenuate the vasoconstrictor actions of A II on the superficial renal microvasculature and minimize changes in QA, SNGFR, and total GFR. It is likely that an interaction between A II and PG may be important in pathophysiological conditions in which endogenous A II levels are elevated.

Angiotensin II↗
PubMed1978

Evidence for a parathyroid hormone-dependent influence of calcium on the glomerular ultrafiltration coefficient.

Experiments were performed on 36 plasma-expanded Munich-Wistar rats to examine the effects of acute hypercalcemia on the determinants of glomerular ultrafiltration. Elevation of total plasma calcium concentration to an average value of 13.2 +/- 0.5 mg/dl, by acute infusion of calcium chloride into nonthyroparathyroidectomized (non-TPTX) rats, resulted in significant declines in single nephron and whole kidney glomerular filtration rate. These declines were due primarily to a fall in the glomerular capillary ultrafiltration coefficient (Kf), to a mean value approximately 60% below that determined in the pre-infusion period. These changes were not seen in a separate group of sham-treated non-TPTX rats. It is of interest that these effects of acute hypercalcemia were largely abolished in rats that underwent acute TPTX before hypercalcemia. Infusion of a submaximally phosphaturic dose of parathyroid hormone, together with calcium chloride, into a second group of acute TPTX rats, however, had the effect of reproducing the striking declines in filtration rate and Kf noted in non-TPTX rats given calcium chloride alone. These findings suggest that the decline in filtration rate associated with hypercalcemia is due largely to the reduction in Kf, the latter dependent upon the presence of parathyroid hormone.

Animals↗
PubMed1978

Permselectivity of the glomerular capillary wall. Facilitated filtration of circulating polycations.

To examine the electrostatic effects of fixed negative charges on the glomerular capillary wall, polydisperse [(3)H]DEAE dextran, a polycationic form of dextran, was infused into 10 Munich-Wistar rats. Fractional clearances of DEAE ranging in radius from 18 to 44A were determined in these rats, together with direct measurements of the forces and flows governing the glomerular filtration rate of water. These results were compared with data previously obtained in Munich-Wistar rats receiving tritiated neutral dextran (D) and polyanionic dextran sulfate (DS). Measured values for the determinants of the glomerular filtration rate of water in rats given DEAE were found to be essentially identical to those in rats given either D or DS. In addition, DEAE was shown to be neither secreted nor reabsorbed. Fractional clearances of polycationic DEAE were increased relative to both D and DS, the increase relative to D being significant for effective molecular radii ranging from 24 to 44A. Fractional DEAE clearances were also measured in a separate group of six Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Fractional DEAE clearances in NSN rats were reduced significantly, relative to values measured in normal rats, for effective DEAE radii ranging from 18 to 42A. Moreover, in NSN rats, fixed negative charges on the glomerular capillary wall were greatly reduced, relative to non-NSN rats, as evidenced by a reduction in intensity of colloidal iron staining. Thus, in NSN rats, DEAE clearances were essentially indistinguishable from values obtained with both neutral D and polyanionic DS.

Animals↗
PubMed1977

Mechanisms of the defect in glomerular ultrafiltration associated with gentamicin administration.

Micropuncture studies were performed in three groups of Munich-Wistar rats: eight normal hydropenic controls (group I) and two groups (eight rats each) which were treated with gentamicin in doses of either 4 or 40 mg/kg/day for ten days (groups II and III, respectively). Following gentamicin administration, values for single nephron (SN) GFR were reduced markedly, from the control mean of 31 +/- 0.7 (SEM) nl/min to 22.4 +/- 1.5 and 20.5 +/- 0.9 for groups II and III, respectively. Declines in whole kidney GFR paralleled these falls in SNGFR. The primary cause of the reduction in SNGFR was a marked decline in glomerular capillary ultrafiltration coefficient, Kf, in both gentamicin treatment groups. None of the other determinants of glomerular ultrafiltration were significantly affected in the low dose group (group II). In the high dose group (group III), however, mean values for initial glomerular plasma flow rate and mean transglomerular hydraulic pressure difference were significantly lower than in the control group, accounting for the somewhat greater decline in SNGFR observed in group III. Electron microscopic examination of kidney tissue from rats treated with both doses of gentamicin revealed no obvious abnormalities of the glomerular capillary wall, whereas the previously described morphologic aberrations of proximal convoluted tubule cells were readily demonstrable.

Animals↗
PubMed1977

Dynamics of glomerular ultrafiltration. IX. Effects of plasma protein concentration.

Experiments were carried out on 42 Munich-Wistar rats with surface glomeruli accessible to micropuncture to investigate the effects of reduction in systemic plasma protein concentration. CA, and thus afferent oncotic pressure, IIA, on the determinants of glomerular ultrafiltration. In animals in which CA was reduced by a variety of maneuvers, observed values for single-nephron GFR were lower than values predicted by the Starling relation, when the latter were calculated assuming that the observed increase in the net driving pressure for ultrafiltration (due to the reduction in IIA) was the only factor perturbed. In all experimental conditions where CA was reduced, rats were invariably observed to be at filtration pressure disequilibrium, permitting calculation of unique values of the ultrafiltration coefficient, Kt. In all low-CA groups, mean values of Kf were uniformly lower than values obtainedin normoproteinemic control animals. The failure of SNGFR to rise to predicted values when CA is reduced is therefore due to the concomitant reduction in Kf. No morphological basis for this reduction in Kf was discerned.

Animals↗
PubMed1977

Mechanism of angiotensin II-induced proteinuria in the rat.

To investigate the mechanism(s) of angiotensin II-induced proteinuria, polydisperse [3H]dextran (D) (radius = 18-42 A) was infused into seven Munich-Wistar rats before and during intravenous infusion of angiotensin II (AII), 0.35 microgram/kg per min. During AII infusion, UprotV rose approximately twofold, and the fractional clearances of D [(U/P)D/(U/P)In] increased significantly for dextrans with radii greater than 22 A. Single nephron filtration fraction increased, due to a measured rise in the glomerular transcapillary hydraulic pressure difference from 34 to 43 mmHg. Near constancy of single nephron glomerular filtration rate resulted, however, from the offsetting effect of a decrease in glomerular plasma flow rate from 83 to 60 nl/min. These measured hemodynamic changes were found, by the use of pore theory, to account to a large extent for the measured increases in (U/P)D/(U/P)In. In seven other rats, fractional clearances of polyanionic dex-ran sulfate (a more reliable marker of albumin filtration than D) were also found to increase significantly with AII, suggesting that the proteinuria induced by AII can be explained, in large part, by hemodynamic factors.

Angiotensin II↗
PubMed1977

Evidence for glomerular actions of ADH and dibutyryl cyclic AMP in the rat.

Experiments were performed on 54 chronically water diuretic Munich-Wistar rats to investigate the effects of various antidiuretic peptides on the determinants of glomerular ultrafiltration. Transition from water diuresis to antidiuresis, induced either by intravenous infusion of 1) exogenous peptides (Pitressin, synthetic arginine vasopressin, or synthetic [1-deamino,4-valine]-8-D-arginine vasopressin) or 2) dibutyryl cyclic AMP, or by stimulation of endogenous ADH release by acute, mild arterial hemorrhage, was associated with near-constant or decreased values for single nephron (SN) and total kidney GFR. Nevertheless, the glomerular transcapillary hydraulic pressure difference (deltaP) uniformly increased with antidiuresis, due to consistent reductions in Bowman's space hydraulic pressure rather than to increases in glomerular capillary hydraulic pressure, the former a consequence of the fall in urine flow rate. In all antidiuretic states, the rats were uniformly observed to be at filtration pressure disequilibrium, permitting calculation of unique values of the glomerular ultrafiltration coefficient (Kf). These values of Kf in antidiuresis were invariably lower than the values obtained during water diuresis. Whether these effects of ADH and DBcAMP on deltaP and Kf represent physiological influences in the control of GFR remains uncertain; their offsetting effects in the present studies usually failed to alter GFR appreciably.

Animals↗
PubMed1977

Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules.

To investigate the mechanism(s) of increased filtration of serum proteins after glomerular injury, polydisperse samples of uncharged [(3)H]dextran (D) or anionic [(3)H]dextran sulfate (DS) were infused into 14 control and 16 puromycin aminonucleoside- (PAN) treated Munich-Wistar rats. Fractional clearances of D or DS ranging in radius from 18 to 42A were determined in these rats, together with direct measurements of the forces governing the glomerular filtration rate of water. Whole kidney and single nephron glomerular filtration rates were approximately 40% lower in PAN-treated rats, relative to controls, due mainly to a marked reduction in the glomerular capillary ultrafiltration coefficient and, to a lesser extent, to a small reduction in glomerular plasma flow rate as well. In PAN-treated rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and both D and DS were shown to be neither secreted nor reabsorbed. Fractional clearances of uncharged D were reduced after PAN administration, falling significantly for effective D radii from 22 to 38A. Utilizing a theory based on macromolecular transport through pores, these results indicate that in PAN-treated rats, effective pore radius is the same as in controls, approximately 44A. In PAN nephrosis, however, the ratio of total pore surface area/pore length, a measure of pore density, is reduced to approximately one-third that of control, due very likely to a reduction in filtration surface area. In contrast to the results with uncharged D, fractional clearances of DS were found to increase after PAN administration for all DS radii studied. These results with D and DS suggest that proteinuria in PAN nephrosis is due, not to an increase in effective pore radius or number of pores, but rather to a diminution of the electrostatic barrier function of the glomerular capillary wall, thereby allowing increased passage of polyanions such as DS and albumin.

Animals↗