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P D Bell

Publications and source records attributed to P D Bell.

At least 55 records · Page 3Linked to original sources
PubMed1989

Direct measurement of basolateral membrane potentials from cells of the macula densa.

At the present time, little is known concerning the electrophysiology of the cells of the macula densa and whether or not these cells are electrically responsive to alterations in luminal fluid composition. To investigate this issue, cortical thick ascending limbs (CTAL) containing macula densa and attached glomeruli were dissected from rabbit kidney and the CTAL perfused in vitro. Basolateral membrane potential (Vbl) was measured with microelectrodes in macula densa cells and, for comparison, in cells of the CTAL. Macula densa Vbl averaged -56.5 +/- 7.6 mV (n = 4) at a (n = 22) at 20 mM NaCl, -35.6 +/- 3.9 mV (n = 16) at 45 mM NaCl, and -25.5 +/- 2.6 mV (n = 32) at 150 mm NaCl. Thus macula densa Vbl depolarized markedly (31 mV) when luminal perfusate [NaCl] was increased from low to high values. In contrast, Vbl measured in CTAL cells averaged -62 +/- 6.1 mV (n = 6) in 45 mM NaCl and did not change significantly as perfusate NaCl was increased to 150 mM. In the presence of 150 mM NaCl, luminal application of furosemide (50 microM) produced a small (3.5 +/- 1.1 mV, n = 16) but statistically significant (P less than 0.02) hyperpolarization in macula densa cells, whereas CTAL cell Vbl hyperpolarized markedly (20 +/- 5.7 mV, n = 6) with addition of furosemide. Finally, neither macula densa cells nor the CTAL cells changed Vbl when 45 mM NaCl solution was made hypotonic by removing mannitol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Angiotensin influences on tubuloglomerular feedback mechanism in hypertensive rats.

The tubuloglomerular feedback (TGF) mechanism was evaluated in the nonclipped kidney of Goldblatt hypertensive rats from both stop flow pressure (SFP) and single nephron glomerular filtration rate (SNGFR) responses to step increases in late proximal perfusion rate from 0 to 40 nl/min. During control conditions, increases in late proximal perfusion rate produced flow dependent decreases in SFP and SNGFR with maximal values of 10.2 +/- 1.0 mm Hg and 12.9 +/- 2.5 nl/min, values similar to those obtained in normal rats. During ACE inhibition (MK 422; 0.6 mg/kg/hr), arterial pressure decreased from 168 +/- 8 to 137 +/- 7 mm Hg and there was a marked attenuation in the magnitude of SFP feedback responses (delta = 2.5 +/- 0.3 mm Hg). SNGFR feedback responses, however, were not significantly impaired. Direct decreases in renal arterial pressure reduced control SFP but SFP feedback responses were maintained, indicating that the attenuated SFP feedback responses during ACE inhibition were not due to decreased arterial pressure. Superimposed infusion of angiotensin II during ACE inhibition partially restored SFP feedback responses. In contrast, norepinephrine infusion did not result in a similar restoration of SFP feedback sensitivity. These results indicate that the nonclipped kidney of Goldblatt hypertensive rats has an intact TGF mechanism as assessed from SFP and SNGFR feedback responses. Furthermore, ACE inhibition attenuates SFP but not SNGFR feedback responses, and systemic angiotensin II infusions can restore SFP feedback responsiveness towards normal.

Angiotensin II↗
PubMed1988

Evaluation of prostaglandins as mediators of tubuloglomerular feedback.

Orthograde and retrograde microperfusion experiments were conducted in Sprague-Dawley rats to evaluate the participation of vasoconstrictive eicosanoids as mediators of tubuloglomerular feedback (TGF) signals. Retrograde perfusion with 160 microM arachidonic acid (AA) added to a hypotonic solution enhanced the stop-flow pressure (SFP) feedback responses compared with those obtained with the control hypotonic solution (delta SFP, 1.6 +/- 0.4 vs. 10.1 +/- 0.7 mmHg with AA). Blockade of thromboxane A2 (TxA2) with the receptor blocker EP 092 or the synthesis inhibitor UK 38485 did not alter the magnitude of the SFP feedback responses obtained with an isotonic solution. Similarly, nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not alter maximal SFP feedback responses. Although indomethacin (5 mM) did induce attenuated SFP feedback responses (delta SFP, 9.5 +/- 0.7 vs. 0.5 +/- 0.4 mmHg with indomethacin), normal feedback responses were restored within 15-90 s after cessation of indomethacin perfusion. Additionally, SFP feedback responses were not inhibited with 5 mM piroxicam, a different cyclooxygenase inhibitor. These data fail to support a role for either TxA2 or lipoxygenase end products as mediators of TGF signals. The rapid restoration of feedback responses after indomethacin exposure and the lack of blockade with piroxicam suggest that transmission of feedback signals is not dependent on cyclooxygenase products.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Calcium antagonists and intrarenal regulation of glomerular filtration rate.

The intrarenal tubuloglomerular feedback mechanism operates at the site of contact between the thick ascending limb and glomerulus where specialized macula densa cells detect changes in tubular fluid composition and transmit information to the smooth muscle cells of the afferent arteriole. Increases in tubular fluid osmolality result in the transmission of vasoconstrictor signals and decreases in the rate of filtrate formation. Recent studies have identified two sites at which cytosolic calcium may play important roles. First, studies indicate that tubuloglomerular mediated vasoconstriction involves calcium mediated excitation contraction coupling of smooth muscle cells of the afferent arteriole. This calcium mediated event is sensitive to calcium channel blockade. Second, recent studies suggest that the macula densa cells may detect changes in tubular fluid osmolality through a cytosolic calcium system. The use of intracellular calcium antagonists further suggests that intracellular calcium mobilization is the primary mechanism responsible for increases in macula densa cytosolic calcium with increases in tubular fluid osmolality. Calmodulin and cyclic AMP may serve as modulators of this cytosolic calcium system. These studies suggest that calcium plays important roles in the regulation of renal hemodynamics.

Animals↗
PubMed1987

Myocardial cell growth and blood pressure development in neonatal spontaneously hypertensive rats.

We evaluated the changing morphologic features of cardiac muscle cells (myocytes) and nuclei from neonatal spontaneously hypertensive rats (SHR) and their parent, normotensive strain Wistar Kyoto rats (WKY) and compared these with increasing heart weight and blood pressure development to determine if alterations in cell growth were present at this early stage of development. Femoral artery blood pressures were obtained from rats at 2 to 5-day intervals from birth to 21 days of age by using a micropipette servo-null pressure recording system. Tritiated thymidine autoradiography was used to study myocyte nuclear development, and isolated myocytes were prepared to evaluate cell-size changes by using a Coulter Counter system (Coulter Electronics, Hialeah, Florida). Heart weight and blood pressure were elevated in SHR when compared to WKY at birth. Myocytes were all mononucleated at birth in both strains and were of equal size, demonstrating that the larger heart mass in SHR was due to an increased number of cells. Heart weight relative to body weight remained greater in SHR when compared to WKY throughout the 28-day study period, but cell numbers became equal in the two strains by the 2nd week. A this time (6 to 9 days postpartum) blood pressure was also similar in both strains, but increased significantly again in SHR by 15 and 21 days of age. Cell maturation occurred earlier in SHR than in WKY as indicated by an earlier development of binucleate myocytes and there was an earlier initiation of hypertrophic myocyte growth in SHR. Increase in SHR cell size occurred at a time when blood pressures were not different, suggesting that greater cell size in SHR than in WKY was not due to differences in blood pressure. Therefore, when compared to the WKY, the SHR had three phases of altered cell growth: a first phase of accelerated hyperplastic growth during the fetal period, and a second phase (6 to 12 days of age) of earlier initiation of hypertrophic cell growth and increased myocyte size. The SHR myocyte changes in the second phase occurred while the SHR and the WKY blood pressures were not significantly different. Finally, in a third phase (at 15 days of age and over), SHR had a sustained increase in myocyte size as well as elevated blood pressure.

Aging↗
PubMed1986

Tubuloglomerular feedback responses in the rat during calmodulin inhibition.

Previously, we have suggested that a cytosolic calcium system participates in the transmission of signals between distal tubular fluid and the glomerular vascular elements. Since the Ca-binding protein calmodulin has been implicated in the intracellular actions of cytosolic Ca, we evaluated the effects of the calmodulin antagonists trifluoperazine (TFP) and calmidazolium (R24571) on tubuloglomerular feedback responses. In the rat, stop-flow pressure (SFP) was measured during retrograde perfusion into the distal tubule at 15 nl/min for 5 min. Perfusion with an isotonic Ringer solution resulted in a decrease in SFP of 12 +/- 1.1 mmHg (n = 34). With the addition of 50-75 microM TFP, SFP was decreased by 11 +/- 1.0 mmHg (n = 24); with 500 microM TFP, SFP feedback responses were 10 +/- 1.2 mmHg (n = 7). During perfusion with 20 microM R24571, SFP decreased by an average of 12 +/- 1.1 mmHg (n = 18). Single-nephron glomerular filtration rate feedback responses during retrograde microperfusion were also unaltered by R24571 (delta 15 +/- 2.5 vs. delta 14 +/- 2.6 nl/min). In the SFP experiments it was observed that the recovery of SFP toward preinfusion values after cessation of perfusion was significantly prolonged in tubules perfused with the calmodulin antagonists. SFP recovery times averaged 65 +/- 5.5 s (control), 104 +/- 9.9 s (50-75 microM TFP), 154 +/- 9.6 s (500 microM TFP), and 116 +/- 9.9 s (20 microM R24571). Accordingly, these results suggest that activation of calmodulin is not required for the transmission of tubuloglomerular feedback signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cyclic AMP-calcium interaction in the transmission of tubuloglomerular feedback signals.

Recent studies have suggested that cytosolic calcium serves in the transmission of signals between distal tubular fluid and glomerular vascular elements. Since cAMP can modify calcium-mediated events, it was of interest to determine if agents that elevate intracellular cAMP could influence feedback responses and to assess the interaction of cAMP and intracellular calcium in the transmission of feedback signals. Stop flow pressure (SFP) was measured in the rat during retrograde microperfusion into the distal tubule at 15 nl/min. SFP averaged 37.5 +/- 0.5 mm Hg and decreased by 12.8 +/- 0.8 mm Hg (N = 44) during perfusion with an isotonic Ringer's solution. Addition of 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, decreased the magnitude of SFP feedback responses; 89 +/- 4.5% (N = 16) inhibition was observed at an IBMX concentration of 500 microM. In addition, SFP decreased by only 3 +/- 1 mm Hg (N = 8) during perfusion with 10 mM dibutyryl cAMP in the presence of a low concentration of IBMX and by 1.6 +/- 0.7 mm Hg (N = 12) during perfusion with forskolin, an agent that stimulates adenylate cyclase activity. Calcium ionophore (A23187) significantly increased the magnitude of SFP feedback responses obtained with IBMX alone from 5 +/- 1.0 mm Hg (N = 9; 250 micron IBMX) to 10 +/- 1.2 mm Hg (N = 11). These results indicate that agents which elevate intracellular cAMP markedly attenuate tubuloglomerular feedback responses and that calcium ionophore can reverse the inhibitory effects of increased cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Two bacteriophages of Clostridium difficile.

Two temperate bacteriophages of differing morphology and host range were isolated by screening 94 isolates of Clostridium difficile. Phage 41 had a 300-nm flexible tail, whereas phage 56 had a shorter tail with a contractile sheath. Electron microscopy of phage 56 lysates exposed to elevated magnesium concentrations showed small virus-like particles which were 21 nm in diameter. The addition of MgCl2 to semisolid agar overlays enhanced both the titer and plaque size of phage 56. Phage 56 was more temperature labile than phage 41 and demonstrated unusual lability in buffer at pH 7.0. One-step growth and adsorption experiments revealed that both phages had latent periods of about 60 min, but phage 56 adsorbed to its indicator strain more efficiently. Phage 56, which was obtained from a toxigenic strain of C. difficile, was used to lysogenize its nontoxigenic indicator strain, but no conversion to toxigenicity was observed in this strain.

Bacteriophages↗
PubMed1985

Prostaglandins in the sodium excretory response to altered renal arterial pressure in dogs.

Acute variations in renal arterial pressure are associated with corresponding alterations in absolute and fractional sodium excretion even under conditions of highly efficient autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). Since prostaglandins recently have been implicated in the regulation of sodium excretion, we investigated the hypothesis that the renal prostaglandin system participates in "pressure natriuresis." Anesthetized sodium-replete dogs were subjected to partial carotid artery constriction to elevate systemic arterial pressure. Under these control conditions, sodium excretion was 103 +/- 18 mueq/min (n = 17) and urinary prostaglandin E2 excretion averaged 4.6 +/- 1.5 ng/min (n = 8). Decreases in renal arterial pressure within the auto-regulatory range reduced sodium excretion (2.1%/mmHg) and prostaglandin E2 excretion (1.7%/mmHg), whereas GFR and RBF were not affected. There was a significant correlation between the changes in sodium and prostaglandin E2 excretion rates (r = 0.932, P less than 0.01). In nine dogs treated with indomethacin, sodium excretion was reduced by 70% while GFR and autoregulatory capability were unaffected. There was a marked attenuation of the effect of changes in arterial pressure on sodium excretion, with this parameter exhibiting changes averaging 0.6%/mmHg (P less than 0.001). These observations suggest that the renal prostaglandin system may exert an important influence on the pressure-natriuresis mechanism.

Animals↗
PubMed1985

Direct visualization of the isolated and perfused macula densa.

Direct examination of the structure and function of the macula densa is compromised by the relative inaccessibility and small size of this cell plaque. We report the isolation and perfusion of rabbit nephron segments with attached glomeruli and the direct visualization of the macula densa with differential interference-contrast microscopy. We used this technique to examine the structural sensitivity of the macula densa to perturbations in luminal osmolality and NaCl concentration. Reducing luminal osmolality from 290 to 70 mosmol/kg by removing NaCl resulted in a dilation of the lateral intercellular spaces that was both reversible and specific to the region of the macula densa. Associated with the dilation of the intercellular spaces was a small (congruent to 10%), but statistically significant, increase in the height of the macula densa cells. These structural events were related to the reduction in luminal osmolality, since isosmotic replacement of NaCl with mannitol resulted in no detectable structural changes. Thus, the macula densa may represent a small water-permeable plaque of cells within the remaining water-impermeable thick ascending limb of Henle's loop.

Animals↗
PubMed1984

Tubuloglomerular feedback-mediated decreases in glomerular pressure in Munich-Wistar rats.

These experiments were performed to evaluate directly measured glomerular capillary pressure and single nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses in Munich-Wistar rats during increased distal flow rate achieved by infusing an isotonic electrolyte solution into unblocked late proximal tubules. Arterial pressure averaged 114 +/- 2 mmHg and proximal tubule pressure was 14 +/- 1 mmHg. In eight tubules, control SNGFR based on distal tubular fluid collections averaged 22 +/- 3 nl/min, decreased to 15 +/- 2.3 nl/min when 10-12 nl/min of perfusate was infused into the late proximal tubule, and further decreased to 9 +/- 1.7 nl/min at an infusion of 20-24 nl/min. In 22 tubules, control glomerular capillary pressure was 55 +/- 1.6 mmHg, decreased to 43 +/- 2.5 mmHg with addition of perfusate into a late proximal tubule at a rate of 24 nl/min, and returned to 53 +/- 3.1 mmHg when perfusion was stopped. In eight nephrons, glomerular capillary pressure was shown to be responsive to smaller increments in the late proximal infusion rate and was reduced by 4 +/- 0.5 and 7 +/- 1.1 mmHg at the intermediate rates of 10 and 15 nl/min, respectively. These results demonstrate that glomerular pressure decreases during increased distal delivery even when the tubule is not blocked. They are consistent with the hypothesis that increases in afferent arteriolar resistance are primarily responsible for feedback-mediated reductions in glomerular filtration rate.

Animals↗
PubMed1983

Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog.

The reason for the failure of glomerular filtration rate (GFR) to exhibit plasma flow dependency during pharmacologic vasodilation remains unclear although it has been suggested on the basis of experiments in rats that vasodilators may lead to a reduction in the glomerular filtration coefficient (Kf). To evaluate the applicability of this hypothesis to the dog, the effects of vasodilation with acetylcholine on glomerular dynamics and Kf were evaluated in two groups of dogs. One group (n = 19) was studied at spontaneous arterial pressures to allow maximum vasodilation to occur. In the other group (n = 5), renal arterial pressure was reduced and maintained at approximately 89 mmHg. Glomerular filtration rate and single nephron glomerular filtration rate were not altered significantly during acetylcholine infusion in either of the two groups. Both whole kidney and superficial filtration fractions decreased significantly. At spontaneous arterial pressures, transglomerular hydrostatic pressure was not altered significantly because of equivalent increases in proximal tubule pressure and in glomerular pressure. In the dogs studied at reduced renal perfusion pressure, glomerular capillary pressure did not change, but proximal tubule pressure increased slightly. Average effective filtration pressures and Kf were not significantly altered during the infusion of acetylcholine either at spontaneous or reduced renal perfusion pressures. These observations indicate that Kf in the dog is not significantly decreased by acetylcholine and that GFR is not affected during infusion of this agent because the effective filtration pressure is not significantly altered.

Acetylcholine↗
PubMed1982

Cytoplasmic calcium in the mediation of macula densa tubulo-glomerular feedback responses.

Within each nephron of the mammalian kidney, a feedback mechanism operating between the macula densa segment of the distal tubule and the afferent arteriole participates in the regulation of glomerular filtration rate. Retrograde microperfusion studies in rats were conducted to test the hypothesis that activation of macula densa cytoplasmic calcium is involved in the transmission of feedback signals to the vascular elements. Perfusion into distal tubules with a hypotonic solution (70 milliosmolar) elicited moderate decreases in glomerular pressure of 6 +/- 0.8 millimeters of mercury. With the addition of a calcium ionophore (A23187) glomerular pressure decreased by 16 +/- 1.1 millimeters of mercury. When a solution devoid of calcium but containing A23187 was used, the feedback response was inhibited. Thus, cytoplasmic calcium within the receptor cells may participate in the transmission of feedback signals to the contractile cells.

Animals↗
PubMed1982

Relationship between tubulo-glomerular feedback responses and perfusate hypotonicity.

Previous studies have established that during orthograde perfusion from a late proximal tubule site, there is a direct relationship between the magnitude of the feedback response and the level of distal tubular fluid sodium chloride concentration. The present study was conducted in the rat to extend this observation by assessing stop flow pressure (SFP) feedback responses during retrograde perfusion into the early distal tubule with solutions varying in total solute concentration and in the anionic constituent. SFP was measured after blockade of the intermediate proximal and late distal tubular segments with wax. Retrograde perfusion was initiated from an early distal tubular site at 15 nl/min. All solutions contained a 38 mOsm/kg matrix base, and the total solute concentration was increased with either sodium chloride or sodium isethionate to achieve osmolalities of 68, 85, and 120 mOsm/kg. For comparison, feedback responses during perfusion with a 120 mOsm/kg choline chloride solution were evaluated. During perfusion with the 120 mOsm/kg solutions, SFP decreased by 13 +/- 1.3 mm Hg with the sodium chloride solution, 12 +/- 1.5 mm Hg with the sodium isethionate solution, and 12 +/- 1.3 mm Hg with the choline chloride solution. During perfusion with solutions having an osmolality of 85 mOsm/kg, SFP decreased by 8 +/- 1.3 mm Hg with sodium chloride and 8 +/- 0.8 mm Hg with sodium isethionate. The 68 mOsm/kg solutions elicited decreases in SFP of 4.4 +/- 0.4 mm Hg and 5 +/- 0.5 mm Hg. During perfusion with the 38 mOsm/kg matrix solution, SFP decreased by an average of 1.4 +/- 0.9 mm Hg. Linear regression analysis revealed a 1 mm Hg decrease in SFP for every 7.7 mOsm/kg decrease in perfusate osmolality below 120 mOsm/kg. These results confirm previous findings that the magnitude of the feedback response is associated closely with the concentration of the perfusate over a narrow range from 38 to 120 mOsm/kg. Since the responses with sodium isethionate solutions were similar to the responses obtained with sodium chloride containing solutions, these studies provide evidence that the magnitude of the feedback responses are not specifically dependent on alterations in chloride concentration.

Animals↗
PubMed1982

Influence of bradykinin and papaverine on renal and glomerular hemodynamics in dogs.

Although it is recognized that vasodilator-induced increases in renal plasma flow are not associated with increases in glomerular filtration rate (GFR), the mechanism responsible for the failure of GFR to exhibit plasma flow dependency under these circumstances remains uncertain. To evaluate this problem further, the effects of intra-arterial infusion of two vasodilators, bradykinin (n = 7) and papaverine (n = 6), on renal hemodynamics and glomerular function of dogs were determined. Both agents increased renal blood flow; however, GFR and single nephron GFR (SNGFR) remained unchanged during bradykinin infusion and decreased significantly during papaverine infusion. Transglomerular hydrostatic pressure and mean effective filtration pressure were not altered during bradykinin infusion but were significantly reduced by papaverine. Neither agent altered the glomerular filtration coefficient. These observations indicate that, in the dog, the GFR responses during renal vasodilation are dependent primarily on the effective filtration pressure.

Animals↗