Search PubMed⌕ Search

Biomedical subjects

P D Bell

Publications and source records attributed to P D Bell.

At least 73 records · Page 4Linked to original sources
PubMed1982

Luminal and cellular mechanisms for the mediation of tubuloglomerular feedback responses.

The results of our studies indicate that feedback-mediated changes in SFP are most likely the result of receptor cell detection of luminal fluid solute concentration. No specificity for any particular ion in mediating feedback responses could be identified. The detection of luminal fluid solute concentration may involve an intracellular cytoplasmic calcium system. The existence of a receptor cell intracellular calcium messenger system could serve as the link between changes in distal tubular fluid concentration and the alteration in glomerular vascular resistance.

Calcium↗
PubMed1982

Role of a macula densa feedback mechanism as a mediator of renal autoregulation.

The phenomenon of renal autoregulation demonstrates the presence of a sensitive intrarenal mechanism capable of maintaining GFR stable even during extrinsic disturbances that would be expected to alter renal hemodynamics. Substantial evidence has accumulated indicating that autoregulatory capability is dependent on the integrity of normal distal tubule flow dynamics and an intact distal tubuloglomerular feedback mechanism. Several whole-kidney and micropuncture studies have shown that interruption of volume delivery to the distal nephron interferes with autoregulation of renal blood flow (RBF) and GFR. The autoregulatory adjustments are probably localized at the afferent arterioles because the pressure in the larger arterioles does not exhibit autoregulation in response to decreases in renal perfusion pressure. It remains uncertain if the distal tubuloglomerular feedback mechanism is entirely responsible for autoregulatory responses. Data obtained in dog experiments indicate that under conditions of interrupted delivery to the distal nephron, SNGFR responses to decreases in arterial pressure are approximately those expected of a passive system where proximal tubule pressure is allowed to adjust to new steady-state levels with regard to the rapidity with which signals are transmitted to the distal nephron. Whole-kidney experiments indicate that, under conditions of a mild osmotic diuresis, the changes in urine flow following an increase in arterial pressure occur within 1 sec of the initiation of autoregulatory adjustments in vascular resistance. These experiments are consistent with the view that the major fraction of renal autoregulatory adjustments in resistance is mediated by the distal tubuloglomerular feedback mechanism that responds to some component of distal tubular flow and transmits signals to the afferent arteriolar segment of the same nephron.

Animals↗
PubMed1981

Dissociation of tubuloglomerular feedback responses from distal tubular chloride concentration in the rat.

Previous studies have demonstrated that stop-flow pressure (SFP) feedback responses can occur during orthograde perfusion with solutions having low amounts of sodium or chloride. However, retrograde perfusion studies have suggested a specific role for chloride concentration in mediating feedback responses. These studies were conducted to compare SFP feedback responses during orthograde and retrograde perfusion with an artificial tubular fluid solution (ATF) (Cl- = 135 meq/liter) and a Na+ isethionate solution (Cl- = 6 meq/liter). With ATF, increases in perfusion rate from 10 to 35 nl/min led to decreases in SFP of 11 +/- 1.4 mmHg, increases in distal tubular fluid Cl- of 46 +/- 4.9 meq/liter, and osmolality of 58 +/- 10 mosmol/kg. There were significant inverse relationships between SFP and changes in Cl- and osmolality. With Na+ isethionate, SFP decreased by 8.4 +/- 1.0 mmHg, osmolality increased by 43 +/- 8 mosmol/kg, and Cl- did not change. There was a significant relationship between SFP and osmolality, but not with Cl-. During retrograde perfusion at 15 nl/min, SFP decreased by 12 +/- 1.2 mmHg with ATF and by 12 +/- 1.2 mmHg with Na+ isethionate. These results demonstrate that feedback-mediated decreases in SFP can occur in the absence of concomitant increases in distal Cl- and suggest that the receptor system does not have a unique and specific requirement for chloride.

Animals↗
PubMed1981

Role of feedback mechanism in renal autoregulation and sensing step in feedback pathway.

The unique morphology of the juxtaglomerular complex has resulted in many investigations evaluating its potential physiological roles. One hypothesis that has stimulated considerable interest is that feedback signals originating from distal tubule cells, presumably at the macula densa segment, participate in the phenomenon of renal autoregulation. Data obtained from dog experiments indicate tha autoregulation of single nephron glomerular filtration rate (SNGFR) is most consistently observed when fluid delivery to the early distal tubule is not interrupted. In contrast, techniques that interfere with normal orthograde fluid delivery to the distal nephron have usually resulted in increases in SNGFR and an inability to exhibit appropriate autoregulatory responses to decreases in arterial pressure. There is considerable uncertainty concerning the nature of the intraluminal component of the early distal tubule fluid responsible for initiating feedback responses. The studies reported in this paper have indicated that feedback mediated decreases in stop-flow pressure and SNGFR in response to increases in distal microperfusion rate can occur with a variety of artificial perfusion solutions, including solutions that contain low concentrations of chloride, sodium, or total electrolytes. Microperfusion studies in the rat have demonstrated that feedback mediated decreases in stop-flow pressure can occur in the absence of associated increases in distal tubule fluid chloride concentration. These results are consistent with the concept that some function of distal tubule fluid osmolality or distal tubule solute delivery may participate in the initiation of feedback signals.

Animals↗
PubMed1980

Impaired renal blood flow autoregulation in ischemic acute renal failure.

We used a model of ischemic acute renal failure featuring normal renal blood flow (RBF) to evaluate the autoregulatory capability in a preparation having a marked reduction of inulin clearance (GFR). In 10 dogs, we clamped the renal artery for 90 min (experimental); 6 dogs, 1 min only (sham). Approximately 18 hours later, we determined the autoregulatory ability from RBF responses to renal arterial constriction. GFR of the experimental dogs was 10 +/- 4 ml/min, significantly lower than GFR in the sham dogs (43 /+- 9 ml/min). RBF in the experimental dogs (189 +/- 17 ml/min) was not significantly different from that in the sham dogs (206 +/- 32). An autoregulation index, ranging from 0.49 to 1.09 (mean 0.690), was significantly larger than was that of sham dogs, which ranged from zero to 0.23 (mean 0.060). At control arterial pressures, vascular resistance was comparable in both groups; however, at reduced arterial pressures below the normal autoregulatory range, average resistance of the experimental dogs (0.62 +/- 0.12 mm Hg/[ml/min]) was significantly greater than was that of the sham dogs (0.38 +/- 0.06 mm Hg/[ml/min]). These studies indicate that a substantial loss of renal hemodynamic responsiveness follows ischemic injury to the dog even when RBF is maintained within the normal range. The loss of autoregulatory capacity associated with a severely attenuated GFR is consistent with a role for tubular flow in the normal mechanism of autoregulation.

Acute Kidney Injury↗
PubMed1979

Glomerular filtration dynamics in the dog during elevated plasma colloid osmotic pressure.

To determine if the glomerular filtration coefficient (Kf) of the dog is influenced by changes in plasma colloid osmotic pressure (COP), we conducted micropuncture experiments in dogs given concentrated albumin solutions. In one group (N = 9), filtration dynamics were evaluated following infusion of 450 to 600 ml of a 25% bovine albumin solution. To minimize the effects of acute volume expansion, we also achieved high COP levels in another group (N = 7) by albumin loading on the day prior to the experiment. In all experiments, renal arterial pressure was reduced to approximately 90 mm Hg to minimize potential errors that might lead to overestimation of single nephron filtration rate (SNGFR) and glomerular pressure (GP). In the acutely expanded dogs, COP increased to 23.0 +/- (SEM) 0.9 mm Hg, SNGFR was 59 +/- 6 nl/min, estimated GP was 61.0 +/- 2.0 mm Hg, proximal tubule pressure (PTP) was 23.0 +/- 1.6 mm Hg, and superficial filtration fraction (SFF) was 0.13 +/- 0.02. A similarly reduced whole kidney filtration fraction was also observed, due almost entirely to a marked increase in renal blood flow. When compared to noninfused control dogs (N = 13), Kf was significantly higher in the dogs with elevated COP, being 5.3 +/- 0.6 nl/min/mm Hg as compared to 3.4 +/- 0.3 nl/min/mm Hg. Average effective filtration pressure (EFP) was 12 +/- 1mm Hg, and EFP at the efferent end of the glomerular capillaries was 8.9 +/- 1.2 mm Hg. In the group infused on the prior day, COP was 20.0 +/- 0.8 mm Hg, SFF was 0.26 +/- 0.01, SNGFR was 70 +/-8 nl/min, GP was 59 +/- 2 mm Hg, and PTP was 19.0 +/- 1.5 mm Hg. Average EFP was 15 +/- 1 mm Hg, and EFP at the efferent end of the capillaries was 7.5 +/- 0.7 mm Hg. kf was 4.85 +/- 0.66 nl/min/mm Hg, a value significantly higher than that obtained in control dogs having a COP of 15.0 +/- 0.6 mm Hg. Furthermore, one group of control dogs (N = 4), expanded with an isooncotic albumin solution, did not exhibit significant changes in Kf even though the degree of plasma volume expansion was similar to the group expanded with concentrated albumin solution. These experiments are consistent with previous findings obtained in the rat that Kf is influenced by the COP, although the changes in Kf appear to be less than they are in the rat. The data indicate that even under these conditions of elevated COP, the filtration process in the dog is characterized by positive filtration pressures throughout the length of the glomerular capillaries.

Albumins↗
PubMed1978

Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog.

Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.

Animals↗
PubMed1975

Absence of estimated glomerular pressure autoregulation during interrupted distal delivery.

Micropuncture studies in dogs have suggested that a distal tubule-to-afferent arteriole feedback system may participate in the autoregulation mechanism at the single-nephron level. To evaluate the effect of interrupted distal delivery on glomerular capillary pressure (GP) and its autoregulation, the proximal tubule was blocked with oil and maximal stop-flow pressure was measured with a micropressure servo-null system. The GP was estimated from the sum of stop-flow pressure and the plasma colloid osmotic pressure (membrane oncometer). In 18 dogs given a mild mannitol load, average +/- SD control arterial pressure was 118 +/- 16 mmHg, proximal tubule pressure was 24 +/- 5 mmHg, and estimated GP averaged 70 +/- 10 mmHg. There was a highly significant relationship between estimated GP and arterial blood pressure. Similar results were obtained in hydropenic dogs. In response to decreases in renal arterial pressure in individual dogs, stop-flow pressure and estimated GP failed to exhibit autoregulation although autoregulation of renal blood flow, GFR, and proximal tubule pressure was observed over an arterial pressure range of 150-95 mmHg. These results indicate that interruption of normal distal delivery by proximal tubule blockage interferes with the ability of the nephron to autoregulate glomerular pressure. They provide further evidence in support of the concept that a distal tubular feedback mechanism participates, at least in part, in the autoregulatory control of glomerular pressure.

Animals↗
PubMedDate not supplied

Permeability of the macula densa basement membrane area to high molecular weight molecules.

To investigate the permeability properties of the basement membrane beneath macula densa cells and between extraglomerular mesangial cells, thick ascending limbs with attached glomeruli were dissected from rabbit kidney and incubated in a Ringers solution containing either horseradish peroxidase (HRP) (1 mg/ml; molecular weight approximately 40,000) or native or cationic ferritin (both at 5 mg/ml molecular weight approximately 450,000) for 5 and 20 min at room temperature. Tubules were processed for electron microscopy. At both time points, HRP reaction product fully permeated the matrix material between extraglomerular mesangial cells, the basement membrane underneath the macula densa, and also was occasionally located in intercellular spaces and intracellular vesicles within macula densa cells. Similar results were obtained with native and cationic ferritin. In separate experiments, thick ascending limbs with attached glomeruli were perfused for 20 min at room temperature with a Ringer solution containing HRP (1 mg/ml). HRP was found in tubulovesicular bodies within the apical cytoplasm of macula densa cells again indicating that these cells exhibit endocytotic activity. However, HRP did not gain access to intercellular spaces indicating that the apical junctional complex was impermeable to HRP. These results demonstrate that the macula densa basement membrane and matrix material between extraglomerular mesangial cells is permeable to high molecular weight molecules and suggest unhindered diffusion of water and solutes within this area.

Animals↗