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Biomedical subjects

A Fogo

Publications and source records attributed to A Fogo.

103 records · Page 6Linked to original sources
PubMed1989

Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2.

In view of its role as a pro-inflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose-dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (QA), SNGFR and SNFF also fell [126 +/- 7 to 101 +/- 6 nl/min (P less than 0.005), 40.6 +/- 2.1 to 21.5 +/- 2.5 nl/min (P less than 0.005), and 0.33 +/- 0.03 to 0.21 +/- 0.03 (P less than 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 +/- 0.14 to 2.73 +/- 0.19 (P less than 0.005) and 1.32 +/- 0.13 to 1.45 +/- 0.10(10)dyn.s.cm-5 (P less than 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 +/- 0.012 to 0.020 +/- 0.003 nl.s-1.mmHg (P less than 0.025)]. PAF-induced changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2.

Animals↗
PubMed1989

Glomerular actions of endothelin in vivo.

In Munich-Wistar rats, a micropipette was inserted into a first-order branch of the left main renal artery and continuously infused with human/porcine endothelin (0.4 ng/min). Micropuncture measurements revealed substantial differences within the cortical microcirculation of the same left kidney: SNGFR was some 35% lower in glomeruli exposed to endothelin compared with non-endothelin-perfused glomeruli (P less than 0.005). Similarly, glomerular plasma flow rate was some 38% lower in the endothelin-exposed glomeruli (P less than 0.001). The hypoperfusion and hypofiltration in the endothelin-exposed glomeruli reflected an increase in resistances in the afferent and efferent arterioles. There was no difference in the value of the glomerular capillary ultrafiltration coefficient between the two populations of glomeruli. We also studied kidneys that underwent 25 min of renal artery clamping 48 h before study. Antiendothelin antibody infused into one of the branches of the main renal artery ameliorated the vasoconstriction characteristic of postischemic nephrons: within the cortical microcirculation, the SNGFR in glomeruli exposed to antiendothelin antibody was 27.0 +/- 3.1 nl/min as compared with 17.4 +/- 1.7 measured in glomeruli not perfused with the antibody (P less than 0.001). Similarly, glomerular plasma flow rate was higher in the glomeruli exposed to antiendothelin antibody (128.7 +/- 14.4 nl/min vs. 66.6 +/- 5.6, P less than 0.005). Resistances in both the afferent and efferent arterioles were substantially lower in the antibody-exposed glomeruli. It is, therefore, suggested that endothelin, presumably released from damaged endothelium, may play an important intermediary role in the hypoperfusion and hypofiltration observed in postischemic kidneys.

Animals↗
PubMed1988

Effect of heparin on the glomerular structure and function of remnant nephrons.

The development of glomerular structural abnormalities in remnant nephrons, after ablation of renal mass (subtotal nephrectomy), in rats is largely prevented by the daily injection of heparin. To investigate if this protective effect of heparin is due to attenuation of glomerular hyperperfusion, hypertension and hyperfiltration, which develop in remnant nephrons soon after subtotal nephrectomy, we measured various parameters of glomerular hemodynamics at two weeks (Group 1) and four weeks (Group 2) after removal of 1-3/4 of total kidney mass in heparin-treated (Groups 1A and 2A) and untreated (Groups 1B and 2B) Munich-Wistar rats. When compared to normal non-nephrectomized rats (Group 1C), the values for glomerular capillary hydraulic pressure (PGC), glomerular plasma flow rate (QA) and single nephron filtration rate (SNGFR) in remnant nephrons were found to be markedly and similarly elevated in both Groups 1A and 1B, averaging 71 +/- 4 and 73 +/- 4 mm Hg, 229 +/- 41 and 176 +/- 13 nl/min, 58.9 +/- 6.4 and 60.8 +/- 7.8 nl/min, respectively. Thus, glomerular hemodynamic parameters two weeks after subtotal nephrectomy did not differ between untreated and heparin-treated rats. Likewise, heparin treatment did not decrease the values of PGC and SNGFR assessed four weeks after subtotal nephrectomy, with the average values being 65 +/- 2 mm Hg and 83.8 +/- 7.1 nl/min in Group 2A versus 62 +/- 4 mm Hg and 63.7 +/- 6.5 nl/min in Group 2B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Serial micropuncture analysis of single nephron function in subtotal renal ablation.

We developed a series of methodology to analyze function-structure relationship at single nephron level in animal models of chronic renal disease. Micropuncture measurements were repeated to measure single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) in the same nephrons, and subsequently examine the morphology of these glomeruli by serial section histological analysis. Using this approach, a potential causal link between early functional pattern and late structural abnormalities was examined in glomeruli of 10 Munich-Wistar rats up to six weeks after surgical removal of 5/6 total renal mass. After two weeks all SNGFR and PGC values increased uniformly but to varying degrees within each remnant kidney. Thereafter, values for SNGFR were highly variable, many declining while other increased in the same kidney. PGC showed an initial increase with subsequent decrease by four to six weeks. Serial section histological analysis of these same glomeruli revealed that the extent of glomerular sclerosis positively correlated with the functional deterioration, that is, the degree of reduction in SNGFR (P less than 0.01). However, the degree of sclerosis had no tendency to correlate with the levels of SNGFR or PGC recorded in early stage. These studies indicate that pathophysiologic mechanisms other than, or in addition to, early hyperfunction are involved in determining the extent of glomerular structural damage in this model of chronic renal failure.

Animals↗
PubMed1988

Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis.

We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized Munich-Wistar rats. Single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.

Animals↗
PubMed1988

"Intact nephrons" as the primary origin of proteinuria in chronic renal disease. Study in the rat model of subtotal nephrectomy.

Single nephron filtration rate of albumin (SNGFRAlb) was measured in remnant nephrons of Munich-Wistar rats 4-6 wk after subtotal nephrectomy (NPX). Serial thin-section histological analysis was then conducted on the same glomeruli by light microscopy. SNGFRAlb ranged from 1 to 15 times normal. However, a direct relationship between abnormalities of structure and function was not seen, e.g. the glomeruli with the fewest structural abnormalities and marked hyperfiltration often had the highest SNGFRAlb. Moreover, the majority of glomeruli had minimal structural abnormalities. Normalization of the markedly elevated glomerular capillary pressure (PGC) in these glomeruli was accomplished by acute intravenous infusion of verapamil, which decreased SNGFRAlb by 9-83% without affecting the single nephron filtration rate of water (SNGFRH2O). 1-2 wk after subtotal NPX, all glomeruli were hyperfiltering and had elevated PGC. The fractional clearance of larger (greater than 36 A) dextrans was selectively increased in these glomeruli that lacked discernible damage by light microscopy. Verapamil normalized PGC, reduced proteinuria to 48 +/- 4% of baseline, and improved glomerular size selectivity without altering SNGFRH2O. Proteinuria after subtotal NPX thus originates largely from glomeruli with minimal structural abnormalities. The defect in size selectivity is largely attributed to the prevailing high PGC, producing large, nonselective channels on the glomerular capillary wall. The observations raise the possibility that in chronic renal diseases, the reduction in proteinuria often seen after therapeutic measures, including antihypertensive medication, may reflect their functional effect on the relatively intact glomeruli rather than their structure-sparing effect on severely damaged glomeruli, which contribute little to the proteinuria.

Animals↗
PubMed1987

Neck tumour with syncope due to paroxysmal sympathetic withdrawal.

A patient with recurrent squamous carcinoma metastatic to the neck after radical neck dissection and high dose radiation therapy developed paroxysmal hypotensive episodes that were severe, spontaneous and characterised by suppressed sympathetic but not enhanced parasympathetic activity. Intravenous pressors were successful in treating acute episodes but neither drug therapy nor surgical neck exploration reliably prevented syncopal attacks. Glossopharyngeal and/or vagal nerve infiltration by tumour with episodic activation of the afferent limb of the baroreflex arc producing vasodilatation primarily due to sympathetic withdrawal is the likely mechanism of life threatening syncope in this patient.

Adrenergic Fibers↗
PubMed1987

Histiocytosis-X isolated to the cervical spinal cord.

Histiocytosis-X may involve many tissues, including the central nervous system. This report is the first documentation of histiocytosis-X occurring exclusively in the spinal cord. We present a patient with cervical spinal cord disease causing spastic paraplegia, flaccid right arm weakness, and sensory loss. Magnetic resonance imaging of the spinal cord clearly demonstrated the entire lesion. Following surgical decompression and biopsy, the cervical spinal cord was treated with low-dose radiation, which resulted in complete regression of the lesion by radiologic assessment. The child became neurologically normal, and histiocytosis-X has not been detected in other organ systems.

Histiocytosis, Langerhans-Cell↗