PubMed Health⌕ Search

Biomedical subjects

F B Gabbai

Publications and source records attributed to F B Gabbai.

49 records · Page 3Linked to original sources
PubMed1989

A single nephron model of acute tubular injury: role of tubuloglomerular feedback.

A single nephron model of nephrotoxic tubular injury was established to examine the mechanism whereby acute tubular damage contributes to reductions in nephron filtration rate (SNGFR). Acute microperfusion of 0.5 ng of uranyl nitrate (UN) into the early proximal tubule produced a significant reduction (16 to 30%) in SNGFR measured in both distal and proximal tubules of the same nephron and a decrease in absolute proximal reabsorption. Microperfused inulin was retained in the tubule suggesting this finding reflected a true reduction in SNGFR. Concurrent infusion of high dose furosemide (2 x 10(-4)M) and bumetanide (2 x 10(-5) M), but not low dose furosemide (2 x 10(-5) M), prevented the UN induced reduction in SNGFR. High dose furosemide begun after UN perfusion also prevented reduction in SNGFR. Continuous direct measurement of glomerular capillary hydrostatic pressure revealed no change. Distal intratubular Na+ and Cl- concentration increased significantly after UN perfusion. Activation of tubuloglomerular feedback mechanisms best explains the reduction in glomerular ultrafiltration that is characteristic of nephrotoxic forms of tubular injury.

Acute Kidney Injury↗
PubMed1989

Glomerular hemodynamics in pathophysiologic conditions.

Under normal conditions glomerular blood flow and glomerular capillary hydrostatic pressure and hydrostatic pressure gradient are regulated within a narrow range in spite of variations in volume status and blood pressure. Glomerular ultrafiltration rate is normally regulated by the hydrostatic pressure gradient, the systemic oncotic pressure, the rate of nephron plasma flow and the glomerular ultrafiltration coefficient. Although the process of glomerular ultrafiltration is driven by the hydrostatic pressure gradient (delta P), regulation of nephron filtration rate (SNGFR) is not mediated by changes in hydrostatic pressure and the correlation between SNGFR and delta P is very poor. There are certain clinical experimental models in which the glomerular capillary hydrostatic pressure gradient is elevated. These models have been: (1) subtotal nephrectomy model, a model of reduced renal mass, (2) glomerular immune induced injury or glomerulonephritis, (3) most models of systemic hypertension, and (4) certain stages of experimental diabetes mellitus, but the mechanisms vary among the conditions. In most of these clinical models the increase in delta P is associated with a reduction in the glomerular ultrafiltration coefficient. It is also clear that superimposition of hypertension upon models of glomerular immune injury and radical subtotal nephrectomy cause progression of renal dysfunction and glomerulosclerosis. One of the contributing factors to this progression appears to be the elevation in glomerular capillary hydrostatic pressure and pressure gradient. However, other factors have been suggested to play a significant role, such as compensatory hypertrophy and possibly the neurohumoral environment. Therapy of systemic hypertension and administration of cardiovascular drugs which alter glomerular capillary hydrostatic pressure may then modify the rate of progresswion of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of tertatolol on glomerular hemodynamics in the normal Munich-Wistar rat.

Administration of beta-blockers is frequently associated with decreases in both renal plasma flow and glomerular filtration rate (GFR). Tertatolol, a new non-selective beta-blocker, has demonstrated similar systemic effects to other conventional beta-blockers, but tertatolol produces increases in both renal plasma flow and glomerular filtration rate. To evaluate the renal hemodynamic mechanism responsible for the increase in GFR, micropuncture experiments were performed in normal Munich-Wistar rats. Intravenous injection of tertatolol produced a significant increase in GFR and urinary sodium excretion in spite of a decrease in systemic blood pressure. Single nephron glomerular filtration rate was significantly increased due to an increase in single nephron plasma flow related to parallel afferent and efferent arteriolar dilatation. No significant changes in glomerular hydrostatic pressure, transcapillary hydrostatic pressure gradient or the ultrafiltration coefficient were demonstrated with tertatolol. The capacity of tertatolol to increase glomerular filtration rate and to promote sodium excretion without modifying critical glomerular pressures makes this agent a highly attractive antihypertensive drug.

Adrenergic beta-Antagonists↗
PubMed1988

Role of angiotensin II in experimental membranous nephropathy.

Glomerular hemodynamics measurements in rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)] have demonstrated that the appearance of proteinuria 5 days after administration of anti-Fx1A antibody is temporally related to changes in the glomerular ultrafiltration coefficient (LpA). Previous studies in other models of glomerular injury have suggested a significant role for angiotensin II (ANG II) in the glomerular hemodynamic abnormalities. To evaluate the possible role of ANG II in the LpA decrease, converting enzyme inhibitor (CEI) was administered acutely or chronically (5 days before and after induction of PHN) to rats with PHN. Acute ANG II blockade produced a fall in mean arterial pressure (MAP), single-nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption (APR), single-nephron plasma flow, single-nephron blood flow, and glomerular capillary hydrostatic pressure (PG); however, no changes in LpA were detected. Chronic administration of CEI (MK421, 5 mg.kg-1.day-1) in the drinking water was associated with a fall in MAP; however, both SNGFR and APR increased. PG and the transcapillary hydrostatic pressure gradient were unchanged, and LpA remained depressed. These results suggest that reduction of LpA in rats with PHN is ANG II independent and that other mechanisms are required to explain these changes in glomerular hemodynamics.

Angiotensin II↗
PubMed1988

Evaluating hyperfiltration with glycine in hypertensive rats with renal ablation.

Hypertension-induced renal damage is mediated by increased glomerular pressure and flow. These alterations have been evaluated by the renal response to protein or amino acids. To test this assumption, we studied glomerular hemodynamic responses to glycine infusion in rats with reduced renal mass, with and without Goldblatt hypertension. The left kidney was ablated by two thirds in 12 rats, and in 5, hypertension was induced by clipping the right renal artery. Seven normal, unmanipulated rats served as controls. Micropuncture was performed in the left kidney during control and 15% glycine infusion periods, 45 days after surgery. Arterial pressure was higher in hypertensive rats (160.3 mm Hg) than in controls (103.8 mm Hg) and rats with renal ablation (125 mm Hg; p less than 0.05). Higher values of single-nephron glomerular filtration rate and single-nephron plasma flow in rats with renal ablation (63.0, 223.7 nl/min) and hypertension (46.1, 239.7 nl/min) than in controls (28.8, 94.9; p less than 0.05) demonstrated the presence of hyperfiltration. However, glomerular pressure was elevated only in hypertensive rats (40.1 mm Hg), when compared to controls (32.7 mm Hg; p less than 0.05) and rats with renal ablation (33.4 mm Hg; p less than 0.05). Glycine increased single-nephron glomerular filtration rate and single-nephron plasma flow in control rats by 76 and 65%; rats with renal ablation had only partial responses, 35% and 23%, respectively, whereas in hypertensive rats the response was completely abolished. Glycine detected hyperfiltration and unmasked a dysfunction of preglomerular vessels that was greater in hypertensive rats and could contribute to the rise in glomerular pressure and flow and thereby to glomerular damage.

Animals↗
PubMed1988

An evaluation of the role of complement depletion in experimental membranous nephropathy in the rat.

Passive Heymann nephritis (PHN), a model of experimental membranous nephropathy produced by the administration of anti-Fx1A antibody, was studied by micropuncture measurement of glomerular hemodynamics and by assessment of immunologic and morphologic findings. The effect of complement depletion on these parameters was evaluated by administering cobra venom factor. Five days after administration of anti-Fx1A Ab to PHN controls, abnormal proteinuria developed and nephron filtration rate decreased due to modest reductions in nephron plasma flow and major reductions (75%) in the glomerular ultrafiltration coefficient. Glomerular capillary hydrostatic pressure gradient was significantly increased and decreased tubular reabsorption was also evident. Complement depletion prevented abnormal proteinuria and normalized tubular reabsorption and some of the glomerular hemodynamic parameters (nephron plasma flow and glomerular capillary hydrostatic pressure gradient). Values for the glomerular ultrafiltration coefficient, a possible index of membrane damage, were significantly improved (100%) after cobra venom factor treatment, although they remained below normal values. Only minimal differences in glomerular and epithelial cell morphology and appearance of electron-dense material were noted between PHN and PHN + cobra venom factor. These data suggest therefore that both complement-dependent and independent mechanisms contribute to explain the changes in nephron filtration and reabsorption that occur in this model of experimental membranous nephropathy.

Animals↗
PubMed1987

An evaluation of the development of experimental membranous nephropathy.

Heymann nephritis is a rat model of glomerulonephritis with morphologic manifestations of human membranous nephropathy. This model is generated by immunizing rats with Fx1A antigen. Passive Heymann's nephritis (PHN) can be produced by the administration of anti-Fx1A antibody (anti-Fx1A Ab) (with abnormal proteinuria appearing in 5 days). Studies were designed to examine the evolution of temporal changes in protein excretion, the glomerular ultrafiltration coefficient (LpA) and morphology of glomerular capillary three and five days after induction of PHN. Glomerular hemodynamic evaluation by micropuncture in euvolemic rats with PHN revealed normal values for nephron filtration rate (SNGFR), LpA and the glomerular hydrostatic pressure gradient (delta P) at day three, but by day five the whole kidney GFR and SNGFR were decreased, delta P increased and LpA significantly reduced. Glomerular binding of anti-Fx1A Ab increased from 38 micrograms/7.6 X 10(4) glomeruli on day three to 52 micrograms on day five. Immune complex deposits evaluated by immunofluorescence and electron microscopy appeared larger and were better defined on day five than on day three. Epithelial foot process fusion was more extensive on day five than day three. The onset of increased proteinuria correlated temporally with a reduction in LpA on day five, which in turn correlated with increased antibody binding, immune deposit accumulation and fusion of epithelial cell foot processes.

Animals↗
PubMed1987

Analysis of renal function in the two-kidney Goldblatt model.

We analyzed the renal functional responses in all rats 4-6 wk after application of a clip to one renal artery and maintained on either a normal NaCl-intake or a NaCl-depletion protocol utilizing both clearance methods and micropuncture evaluations of glomerular hemodynamics. Although mean arterial pressure (MAP) rose significantly, the response was quite variable and the frequency and degree of hypertension independent of NaCl dietary protocol (142 +/- 7 vs. 137 +/- 6 mmHg, NS). Glomerular filtration rate (GFR) of the unclipped kidney was well maintained regardless of absolute MAP, however, GFR in the clipped kidney was somewhat MAP dependent. The glomerular ultrafiltration coefficient (LpA) was reduced in all clipped rats independent of MAP and dietary NaCl (0.037 +/- 0.002 vs. 0.063 +/- 0.009 nl X s-1 X mmHg-1, P less than 0.05). Glomerular capillary hydrostatic (PG) and glomerular capillary hydrostatic gradient (delta P) were elevated in all clipped rats, regardless of MAP, and to a greater extent in clipped rats maintained on the NaCl-depletion protocol (PG, 59.6 vs. 53.2, P less than 0.05). Among clipped rats, multiple regression analysis revealed no correlation between PG or delta P and the degree of reduction in LpA. The unclipped kidney of the two-kidney, one-clip model is characterized by uniform reductions in LpA independent of the MAP and awake blood pressure produced. Although the increase in PG and delta P may contribute to the reduction in LpA observed, the degree of LpA reduction is independent of the magnitude of elevation in PG and delta P in clipped rats.

Animals↗
PubMed1986

Evaluation of renal functional reserve of contralateral kidney of two-kidney, one clip Goldblatt hypertensive rats.

To evaluate the presence of hyperfiltration in two-kidney, one clip (2K, 1C) Goldblatt hypertensive rats, micropuncture studies of the unclipped kidney were used to examine renal functional reserve (RFR) with glycine (G) infusion in normal (N) rats and 2K, 1C rats. Systemic hypertension in 2K, 1C rats was associated with significantly increased values of single-nephron glomerular filtration rate (SNGFR), glomerular plasma flow (QA) and glomerular capillary hydrostatic pressure (PGC) when compared with N rats. Glycine infusion produced a marked increase in SNGFR, QA and whole-kidney GFR in N rats. In contrast, no changes were observed in these parameters in 2K, 1C rats. Lack of response in 2K, 1C rats was related to the failure of renal vessels to dilate during G infusion. These results suggest that loss of renal functional reserve in systemic hypertension is dependent on an abnormal function of renal vascular resistances.

Animals↗
PubMed1986

Effect of captopril and hydrochlorothiazide on glomerular haemodynamics and histological damage in Goldblatt hypertension with partial renal ablation.

Increased glomerular capillary pressure (GCP) mediates glomerular damage in hypertension. The efficacy of captopril, an angiotensin converting enzyme (ACE) inhibitor, and captopril-hydrochlorothiazide (captopril-TZ) in lowering GCP and preventing glomerular damage was evaluated in rats with two-kidney, one clip (2K, 1C) Goldblatt hypertension and partial ablation of the unclipped kidney. Thirty days after surgery nine rats received captopril, 11 received captopril-TZ and eight served as untreated control rats. Sixty days later systemic hypertension was associated with increased GCP and severe structural damage in the unclipped kidney of C rats. Captopril lowered arterial pressure (AP), and prevented the rise in GCP and structural lesion. Captopril-TZ decreased AP and GCP to a greater extent, but did not reduce structural damage further. Captopril lowered GCP, preventing structural damage; greater reduction of GCP with captopril-TZ did not provide further protection.

Animals↗
PubMedDate not supplied

[Glomerular hemodynamics in the isolated and perfused kidney. Effect of the inhibition of nitric oxide synthase].

The isolated perfused kidney (IPK) is characterized by a normal glomerular filtration rate associated with a very low filtration fraction (FF). This study utilized micropuncture studies in the IPK to investigate: 1) the determinants of the ultrafiltration process responsible for the decrease in FF, and 2) the effect of nitric oxide synthase (NOS) blocker (L-NMMA) on glomerular hemodynamics. Two groups of kidneys were studied, a control group (CTL, n = 6) and an experimental group (EXP, n = 6) in which L-NMMA (0.56mM) was added to the perfusate. Significant differences in perfusate flow rate were required to maintain a constant perfusion pressure in both groups of kidneys. Nephron filtration rate, glomerular capillary hydrostatic pressure gradient and the ultrafiltration coefficient were similar between groups and identical to the ones obtained with in vivo micropuncture studies. Both afferent and efferent glomerular resistances were significantly reduced, although L-NMMA administration increased significantly both resistances. Altogether, these data demonstrate that 1) the IPK is an excellent preparation to evaluate the effect of different agents on glomerular pressure and/or membrane permeability in the absence of systemic effects; 2) the decrease in glomerular resistances leads to a significant increase in perfusate flow required to maintain glomerular pressure within normal range, and 3) in the absence of any systemic effect, NOS blocker increases both afferent and efferent arteriolar resistances.

Animals↗