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Biomedical subjects

F B Gabbai

Publications and source records attributed to F B Gabbai.

At least 19 recordsLinked to original sources
PubMed1996

Effect of angiotensin II on the renal response to amino acid in rats.

Administration of the nitric oxide (NO) synthase blocker, N(G)-monomethyl L-arginine prevents the increase in glomerular filtration rate (GFR) normally observed with glycine, an effect that is restored by angiotensin II (AII) blockers. These findings suggest that changes in NO and AII dictate the presence or absence of renal vasodilation during amino acid (AA) infusion. We examined the effect of branched-chain (BCAA) and non-branched-chain (NBCAA) AA on GFR, NO, and AII to determine if abnormal NO or AII responses could explain the absence of vasodilation with BCAA. Our findings demonstrated that NBCAA increased GFR and NO and did not modify AII, either plasma (AIIp) or kidney (AIIk) AII. The response with BCAA was strikingly different. L-Valine increased GFR without modifying NO or AII. L-Leucine increased AIIk and NO but did not increase GFR. Administration of AII blockers (captopril or losartan) was associated with an increase in GFR during infusion of leucine. Single nephron studies demonstrated that increased AIIk with L-leucine was associated with decreased absolute proximal reabsorption and probably activation of the tubuloglomerular feedback. An AA-specific increase in AIIk is critical to inhibition of the normal renal response to AA infusion. NO generation is an important mediator but not the sole mechanism that determines the increase in GFR during amino acid infusion.

Amino Acids↗
PubMed1996

Renal response to blood pressure elevation in normal and glomerulonephritic rats.

Concurrent renal disease appears to augment greatly the adverse effects of systemic hypertension on renal function and the development of glomerulosclerosis. This study examined the effects of systemic hypertension and treatment of hypertension in groups of normal non-nephritic rats and rats submitted to 16 wk of glomerulonephritis induced by the administration of anti-glomerular basement membrane antibody. Hypertension was produced by application of a clip to the right renal artery and blood pressure was treated with an angiotensin-converting enzyme (ACE) inhibitor, quinapril. Glomerulosclerosis of two types developed: a diffuse type that is characteristic of anti-glomerular basement membrane glomerulonephritis, and a focal segmental glomerulosclerosis that is characteristic of systemic hypertension. Glomerulonephritis significantly reduced the capacity of ACE inhibitors to decrease systolic blood pressure in awake animals. In addition, glomerulonephritis produced significant effects on plasma angiotensin II concentrations, whereby ACE inhibition no longer lowered plasma angiotensin II levels and in fact produced an increase. Glomerular capillary hydrostatic pressure and hydrostatic pressure gradient correlated with systolic blood pressure and with the incidence of focal glomerulosclerosis in non-nephritic rats. However, in glomerulonephritis, systolic blood pressure no longer correlated with glomerular capillary pressure, and glomerular capillary pressure no longer correlated with the development of glomerulosclerosis, although systolic blood pressure did correlate with the degree of focal segmental glomerulosclerosis. Concurrent glomerulonephritis strongly conditions the effects of superimposed hypertension by altering the relationship between systemic blood pressure and glomerular capillary hydrostatic pressure and by decreasing the response of hypertension to therapy.

Angiotensin II↗
PubMed1996

Activities of nitric oxide in normal physiology and uremia.

Nitric oxide (NO) generated from arginine exerts a variety of renal and extrarenal physiological and pathophysiological effects. NO is generated by two types of nitric oxide synthases: acutely responsive, constitutive NOS and slower, more persistent inducible NOS (iNOS). The latter is transcriptionally dependent, often stimulated by cytokines. NO regulates glomerular ultrafiltration, tubular reabsorption, and intrarenal renin secretion; many of these renal effects are mediated by interactions with angiotensin II and adrenergic (alpha 2) activity. Decreased NO activity also enhances tubuloglomerular feedback activity, which could contribute to renal vasoconstriction, NaCl retention, and elevated blood pressure. Loss of renal function could influence NO activity via: (1) endothelial dysfunction; (2) decreased arginine synthesis by kidney; (3) responses to arginine analogs that act as NOS inhibitors; (4) increased cytokine activity; and (5) altered oxidation:reduction status of cells, etc. For example, platelet dysfunction in uremia may be caused by cytokine-induced iNOS activation. Moreover, acutely responsive, constitutive NOS activity may be depressed in progressive loss of renal function. Decreased NO activity might contribute to baroreceptor dysfunction observed in hypertension and progressive renal disease. Studies of the impact of uremia suggest that iNOS may be chronically stimulated by cytokines, whereas acutely responsive, constitutive NOS activity may be concurrently depressed.

Animals↗
PubMed1995

Interactive control of renal function by alpha 2-adrenergic system and nitric oxide: role of angiotensin II.

We studied the role of angiotensin II (AII) in the interactive control of renal function by the alpha 2-adrenergic system and nitric oxide (NO) in adult male Munich Wistar rats 5-7 days after ipsilateral renal denervation (DNX). Renal micropuncture was used under euvolemic conditions before (period 1) and during (period 2) systemic inhibition of NO synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) in three groups. Group 1 served as a DNX control. In group 2, the alpha 2-adrenergic agonist B-HT 933 (BHT) was infused systemically throughout the experiment. In group 3, the AII-receptor blocker, Iosartan (LOS), was infused before period 2 as well as throughout infusion of BHT. L-NMMA increased blood pressure (BP) to a similar degree in all three groups. In group 1, infusion of L-NMMA did not affect glomerular hemodynamics or tubular function. With BHT in group 2, L-NMMA reduced absolute proximal tubular reabsorption (APR) and by reducing nephron plasma flow (SNPF) and glomerular ultrafiltration coefficient (LpA) caused nephron filtration rate (SNGFR) to decrease, a response described in innervated kidneys. LOS in group 3 abrogated the BHT-facilitated reduction of LpA and SNGFR but not of SNPF and APR in response to L-NMMA. In group 1, urinary sodium excretion (UNaV) did not change and urinary flow rate (UV) increased slightly in period 2. L-NMMA combined with BHT, however, exerted a profound diuresis and natriuresis in group 2. These effects were further exaggerated with LOS. In a fourth group of DNX rats. LOS given alone before period 2 did not affect SNGFR, SNPF, LpA, APR, UV, or UNaV. We conclude that after subacute renal denervation alpha 2-adrenergic activation sensitizes (a) LpA to reduction by NOS inhibition through an AII-dependent mechanism, and (b) SNPF and proximal tubular reabsorption to reduction by L-NMMA regardless of the AII activity. Furthermore, our results suggest a potential role for the alpha 2-adrenergic system and AII in the diuretic and natriuretic effect of systemic NOS inhibition.

Angiotensin II↗
PubMed1995

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide.

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5-9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

Analysis of Variance↗
PubMed1995

Role of angiotensin in the regulation of renal response to proteins.

Intrarenal and extrarenal humoral factors have been proposed as mediators and modulators of the renal hyperemic response to amino acid infusion. Among the potential modulators, angiotensin II (AII) constitutes the most important candidate due to its critical role in the control of glomerular and tubular function. The modulatory effect of AII has been assessed by (1) measuring the changes in plasma renin activity (PRA)/AII during the normal hyperemic response, and (2) by assessing the levels of PRA/AII and the response to AII-suppressing agents in conditions with no vasodilatory response during amino acid infusion. Administration of a protein load in normal animals or humans does not modify PRA/AII. Absence of a vasodilatory response in various experimental conditions (nitric oxide blockade in normal rats, experimental models of hypertension, diabetes mellitus, chronic glomerulonephritis, cyclosporine administration) is characterized by a significant decrease in proximal tubular reabsorption during amino acid infusion. Converting enzyme inhibitors or AII receptor antagonist restore normal tubular function and the increase in glomerular filtration rate during amino acid infusion. Absence of a vasodilatory response is also associated with increases in kidney AII levels in some of these conditions. These results suggest that (1) AII modulates the amino acid-induced hyperemia through its inhibitory effect on proximal tubular reabsorption and activation of the tubuloglomerular feedback system, and (2) that the expression of the modulatory effect of AII may depend on the interaction between AII and other intrarenal systems like nitric oxide.

Amino Acids↗
PubMed1995

Renal reserve in patients with high blood pressure.

The mechanism by which hypertension produces renal damage remains poorly defined. Experimental evidence suggests that glomerular hypertension/hyperfiltration constitutes a potential mechanism by which hypertension leads to chronic renal failure. Renal functional reserve has been used to investigate the presence or absence of hyperfiltration, both in experimental animals and humans. Micropuncture studies using the two-kidney, one-clip hypertension model have shown that glomerular hypertension/hyperfiltration is associated with loss of renal functional reserve. However, loss of renal functional reserve in this experimental model is not always indicative of hyperfiltration because some antihypertensive agents (Verapamil, Losartan) correct glomerular hypertension/hyperfiltration, but do not restore renal reserve. Renal reserve has also been evaluated in patients with essential hypertension. Some investigators have shown that hypertension is associated with loss of renal functional reserve which can be restored in some studies with antihypertensive therapy. However, normal renal reserve has also been shown in hypertensive patients. Altogether, these data suggest that renal functional reserve cannot be used to assess the role of hemodynamic mechanisms in hypertension-induced renal injury. Long-term follow-up studies are required to establish if loss of renal reserve is indicative of risk factors leading to renal failure in patients with systemic hypertension.

Animals↗
PubMed1994

Does chromostatin influence catecholamine release or blood pressure in vivo?

Although the structure of chromogranin A (CgA) is now known, its ultimate physiological role remains elusive. Recently, an interior fragment of CgA [CgA(124-143)], also called chromostatin, was reported to suppress catecholamine release from chromaffin cells in vitro. We therefore explored chromostatin's biological actions when administered in vivo to anesthetized rodents with normal (Wistar-Kyoto rats) or elevated blood pressure (spontaneously hypertensive rats). Neither mean arterial pressure nor plasma epinephrine concentrations were significantly altered following either chromostatin or vehicle administration. Plasma norepinephrine, on the other hand, tended to rise throughout all studies, with the rise reaching statistical significance only in the SHR subgroup receiving chromostatin. We conclude that, unlike its actions in vitro, chromostatin does not appear to suppress catecholamine release or modulate blood pressure in vivo.

Animals↗
PubMed1994

Glomerular hemodynamics in cell-free and erythrocyte-perfused isolated rat kidney.

The cell-free isolated perfused kidney (IPK) is characterized by normal glomerular filtration rate (GFR) and very low filtration fraction (FF). Addition of erythrocytes to the perfusate (IEPK) increases FF while maintaining "normal" GFR levels. Micropuncture studies were performed in IPK and IEPK to establish the determinants of the glomerular ultrafiltration process responsible for low FF in IPK and to evaluate the impact of the addition of erythrocytes on these determinants. Nephron filtration rate was similar in IPK and IEPK (40 +/- 4 vs. 39 +/- 4 nl/min), whereas nephron perfusate flow was significantly higher in IPK (1,247 +/- 100 vs. 112 +/- 13 nl/min), leading to a superficial nephron FF of 3.4 +/- 0.2% in IPK and 36 +/- 2% in IEPK. Glomerular hydrostatic pressure (PG) and transcapillary hydrostatic pressure gradient (delta P) were 53 +/- 2 and 33 +/- 1 mmHg, respectively, in IPK and 51 +/- 3 and 34 +/- 2 mmHg in IEPK, all normal values. Glomerular arteriolar resistances were significantly lower in IPK than in IEPK, and the glomerular ultrafiltration coefficient (LpA) was significantly lower in IPK (0.053 +/- 0.010 vs. 0.100 +/- 0.020 nl.s-1.mmHg-1), but both values are within the normal in vivo range. These results demonstrate that low FF in IPK is not due to decreased delta P or LpA values but to the high renal perfusion rate required to maintain normal PG and delta P values. Addition of erythrocytes increases glomerular arteriolar resistances and restores glomerular hemodynamics to a pattern nearly identical to in vivo conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Water and protein permeability is regulated by the glomerular epithelial slit diaphragm.

The glomerular barriers to water and macromolecular movement were examined 2 and 24 h after the administration of a monoclonal antibody (mAb) specific to an antigen located on the epithelial slit diaphragm and the external aspect of the glomerular basement membrane. By micropuncture techniques 2 h after mAb administration, single-nephron GFR (SNGFR) and plasma flow were unchanged but the glomerular capillary hydrostatic pressure gradient and glomerular capillary hydrostatic pressure were increased and the glomerular ultrafiltration coefficient (LpA) decreased to values that were 50% of the normal control. There was no increase in urinary protein excretion at 2 h. However, at 24 h after mAb, nephron plasma flow (SNPF) and SNGFR increased and the glomerular ultrafiltration coefficient returned to values indistinguishable from the normal control. At 24 h, there was a marked increase in protein excretion. The administration of meclofenamate decreased values for SNGFR and SNPF to normal. Immunoglobulin G was exclusively bound to glomerular capillary walls in a linear or continuous fashion at 2 h, but in a discontinuous, granular pattern at 24 h. These studies suggest that after mAb, important limiting glomerular barriers for hydraulic conductivity and protein excretion reside on the epithelial aspect of the glomerular capillary basement membrane, specifically at the level of the slit diaphragm. Studies also suggest that alterations in glomerular capillary hydraulic conductivity can be effectively separated from increases in macromolecular permeability.

Animals↗
PubMed1994

Glycine prevents toxic tubular cell injury.

Glycine prevents tubular injury as suggested by in vitro cell culture studies, studies in the isolated perfused kidney, and in vivo studies. We have previously demonstrated that intratubular administration of uranyl nitrate (UN) produces proximal tubular cell injury and decreases proximal tubular reabsorption (APR). The decrease in APR activates tubuloglomerular feedback and lowers nephron filtration rate (SNGFR). This study was designed to evaluate if glycine administration could prevent the decrease in SNGFR after UN administration and if maintenance of SNGFR was due to tubular cell cytoprotection or suppression of the tubuloglomerular feedback. Administration of 0.65 ng of UN into the early proximal tubule was associated with a decrease in distal SNGFR (SNGFRD) from 29 +/- 2 to 24 +/- 2 nL/min (p < .05) and late proximal SNGFR (SNGFRLP) from 37 +/- 2 to 26 +/- 2 nL/min, and APR from 14 +/- 1 to 10 +/- 1 nL/min. Systemic administration of glycine (20 g/dL, 1.4 mL/h) was associated with significant increases in SNGFRD and SNGFRLP, and APR (38 +/- 3, 44 +/- 3, and 15 +/- 2 nL/min). UN administration did not affect APR or SNGFR in glycine-treated rats. These findings demonstrate that glycine prevents UN-induced decreases in SNGFR through a cytoprotective effect on proximal tubular cells.

Animals↗
PubMed1994

Renal functional reserve in experimental chronic glomerulonephritis.

Loss of renal functional reserve, that is, absence of the glomerular vasodilatory response to amino-acid infusion, has been interpreted as equivalent to glomerular hyperperfusion/hypertension, and therefore proposed as a marker of high risk for progressive glomerular sclerosis. To substantiate the validity of this hypothesis we evaluated the renal response to glycine and the extent of glomerular damage 10-12 weeks after induction of anti-glomerular basement membrane glomerulonephritis with or without superimposed clip hypertension. Untreated rats and rats chronically treated with quinapril, a converting-enzyme inhibitor, were studied. In untreated groups, loss of renal functional reserve was demonstrated since GFR, single-nephron GFR (SNGFR) and plasma flow (SNPF) did not increase during glycine infusion. The absence of renal reserve was associated with glomerular hyperfusion/hypertension, and development of proteinuria and glomerulosclerosis. Quinapril reduced proteinuria and diffuse sclerosis in anti-glomerular basement membrane GN, and decreased blood pressure and segmental glomerulosclerosis in antiglomerular basement membrane GN with superimposed clip hypertension. Both treated groups demonstrated a restoration of renal functional reserve, as depicted by increases in GFR, SNGFR, and SNPF after glycine, despite persistence of glomerular hyperperfusion/hypertension. These data demonstrate that renal functional reserve testing, although it does not detect glomerular hyperperfusion/hypertension, can provide information on the progression of glomerular damage.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Role of mesangial cell in glomerular response to volume and angiotensin II.

We have examined the physiological role of the mesangial cell in the regulation of glomerular hemodynamics utilizing mesangial cell lysis by the administration of antithymocyte antibody serum (ATS) 24 h before micropuncture evaluation. Plasma volume expansion (PVE) in normal NaCl-depleted rats increased single-nephron glomerular filtration rate (SNGFR) by 30% because of increases in single-nephron plasma flow (SNPF), whereas glomerular capillary hydrostatic pressure (PG) remained constant. SNGFR did not increase with PVE in NaCl-depleted ATS rats despite increases in SNPF, and PG increased significantly (51 +/- 2 to 67 +/- 3 mmHg) because of afferent arteriolar dilation, whereas efferent resistance remained elevated. Angiotensin II (ANG II) infusion in normal rats decreased SNGFR because of reductions in SNPF and the glomerular ultrafiltration coefficient (LpA), whereas the hydrostatic pressure gradient (delta P) increased. In ATS rats ANG II infusion did not change SNGFR, LpA, or delta P. These in vivo studies suggest that the mesangial cell plays an important role in the regulation of LpA, efferent arteriolar resistance, and the regulation of PG, whereas this cell exerts little effect on the afferent arteriole.

Angiotensin II↗
PubMed1993

Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension.

Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.

Adrenal Medulla↗
PubMed1993

Arginine feeding modifies cyclosporine nephrotoxicity in rats.

Glycine (G) infusion causes renal vasodilation mediated by nitric oxide (NO). Cyclosporine A (CsA) nephrotoxicity is characterized by preglomerular vasoconstriction and decreased efferent arteriolar tone probably related to reduced NO and angiotensin II, respectively. L-Arginine (ARG) is a precursor to NO. To test the hypothesis that chronic CsA decreases renal NO activity, we compared the glomerular hemodynamic response to glycine infusion in rats after 8 d of CsA (30 mg/kg per d s.c.), CsA and ARG (1.6 g/kg per d p.o.) (A/CsA), and in two groups of pair-fed controls (CON, A/CON). Single nephron GFR (SNGFR), single nephron plasma flow (SNPF), glomerular capillary hydrostatic pressure gradient (delta P), proximal tubular reabsorption (APR), and kidney tissue angiotensin II (AIIk) were measured before and during G. CsA was associated with baseline decrements in SNGFR, SNPF, delta P, and AIIk, and with a blunted hemodynamic response to G. In CON, ARG did not affect baseline hemodynamics or modify the response to G. In CsA, ARG decreased baseline preglomerular resistance and restored the glomerular hemodynamic response to G. G was associated with a significant increase in AIIk in both CON and CsA. These findings suggest that (a) CsA is associated with decreased AIIk, and (b) CsA may diminish NO activity within the kidney, and that this capacity may be partially restored by arginine feeding.

Administration, Oral↗
PubMed1992

Angiotensin II and renal functional reserve in rats with Goldblatt hypertension.

We have previously demonstrated that loss of renal functional reserve (renal response to protein loading) in two-kidney, one clip Goldblatt hypertension is characterized by no change in glomerular filtration rate or single nephron glomerular filtration rate and decreased absolute proximal tubular reabsorption during glycine administration. Captopril restores proximal reabsorption and renal functional reserve in this condition. Because captopril suppresses angiotensin II generation and increases bradykinin, prostaglandins, and potentially nitric oxide, we have investigated the role of angiotensin II blockade in restoring proximal reabsorption and renal functional reserve by comparing captopril with DuP 753, an angiotensin II receptor antagonist, in Goldblatt rats. One month after clipping, two period micropuncture studies (control and glycine) were performed on the unclipped kidney. Normal rats and three groups of clipped rats were studied: an untreated group (HYP), a group treated with captopril (CEI), and a group treated with DuP 753 (DuP) 5 days before micropuncture. Glycine increased glomerular filtration rate, nephron plasma flow, and single nephron glomerular filtration rate in normal rats. Systemic and glomerular hypertension in HYP rats was associated with loss of renal functional reserve and a decrease in absolute proximal reabsorption during glycine. Captopril and DuP 753 normalized systemic and glomerular capillary pressure and prevented the decrease in proximal reabsorption during glycine; however, only CEI rats increased single nephron glomerular filtration rate and glomerular filtration rate after glycine. In conclusion, abnormal responses of both glomerular and tubular function are responsible for the loss of renal functional reserve in Goldblatt rats. Inhibitory angiotensin II activity is responsible for decreasing proximal reabsorption during glycine; however, factors other than angiotensin II limit the glomerular response to glycine.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗