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R C Blantz

Publications and source records attributed to R C Blantz.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1987

Adrenergic and angiotensin II influences on renal vascular tone in chronic sodium depletion.

To examine the role of adrenergic activity on the reduction in nephron filtration rate during chronic sodium depletion in rats, we have measured all the determinants of glomerular ultrafiltration before and after acute unilateral renal denervation. We also examined whether this adrenergic influence was angiotensin II mediated by performing the same protocol with the addition of systemic infusion of an angiotensin-converting enzyme inhibitor, MK 421. The results indicate that both angiotensin II and adrenergic activity contribute to the maintenance of renal vascular resistance during chronic sodium depletion. Acute renal denervation restored nephron filtration rate in chronic sodium-depleted rats (27 +/- 1 to 32 +/- 2 nl/min, P less than 0.05) to control levels (33 +/- 1 nl/min) via reductions in afferent and efferent arteriolar resistances, which also increased nephron plasma flow (85 +/- 5 to 109 +/- 6 nl/min, P less than 0.05). Infusion of MK 421 also increased plasma flow in chronic sodium-depleted rats (116 +/- 11 nl/min, P less than 0.05) through decreases in both arteriolar resistances. Denervation in MK 421-treated rats further increased nephron plasma flow to 137 +/- 10 nl/min (P less than 0.05) only as a result of decreased afferent resistance. The findings indicate that the glomerular hemodynamic changes that characterize chronic sodium depletion are primarily due to the activity of angiotensin II. However, renal adrenergic activity contributes an independent effect on afferent resistance and an effect on efferent resistance via adrenergic effects on angiotensin II.

Angiotensin II↗
PubMed1987

Head-down tilt and restraint on renal function and glomerular dynamics in the rat.

A model utilizing 25 degree head-down tilt (HDT) and incorporated with chronic catheterization and renal micropuncture techniques in rats was employed to study alterations in renal function induced by HDT. Renal function and extracellular volume measurements were performed after 24 h, 4 days, and 7 days of HDT in conscious rats and compared with their own control measurements and to nontilted but similarly restrained rats. After 24 h HDT, glomerular filtration rate (GFR) increased 19 +/- 8% and renal plasma flow (RPF) increased 18 +/- 8% with increases in urine flow rate, Na+, and K+ excretion in conscious rats. These increases after 24 h were associated with an increase in extracellular volume of 16 +/- 3% (P less than 0.01). In the nontilted controls, there was a decrease in extracellular volume after 24 h of suspension. After 7 days of HDT, GFR was decreased by 7 +/- 1% (P less than 0.01), but RPF and extracellular fluid volume were not different from control values. However, RPF and GFR increased in the nontilted rats after 7 days. After 7 days of HDT renal micropuncture studies demonstrated that single-nephron filtration rate was also decreased from 43 +/- 2 to 31 +/- 3 nl/min (P less than 0.05) due solely to reductions in the glomerular ultrafiltration coefficient (0.11 +/- 0.01 to 0.07 +/- 0.01 nl.s-1 X mmHg-1, P less than 0.05). There was a dissociation between GFR and water and Na+ excretion at days 4 and 7 of HDT not observed in the nontilt restraint controls.

Absorption↗
PubMed1987

The glomerular and tubular actions of angiotensin II.

Evidence has accumulated that angiotensin II (AII) exerts multiple influences upon renal function through effects on vascular, glomerular, and tubular structures. Infusion of AII alters glomerular ultrafiltration by decreasing nephron plasma flow, increasing glomerular capillary hydrostatic pressure (PG) and the hydrostatic pressure gradient (delta P) due to increases in both afferent and efferent arteriolar vascular resistance, and effecting a reduction in the glomerular ultrafiltration coefficient (LpA), the product of glomerular membrane hydraulic conductivity and effective surface area for ultrafiltration. Spontaneous increases in intrarenal AII generation, such as observed in chronic NaCl depletion, also produce reductions in nephron plasma flow, increases in delta P, and major reductions in LpA. Angiotensin-converting enzyme inhibitor and saralasin administration prevent these alterations in plasma flow, delta P, and LpA. These AII-induced alterations in LpA may be mediated by AII effects upon the glomerular mesangial cell since AII receptors are expressed and this cell contracts in vitro in the presence of AII. Multiple studies have shown a positive effect of AII (approximately 10(-11) mol/L) on proximal tubular reabsorption, an effect independent of AII effects on peritubular physical factors. These AII effects upon the proximal tubule are clearly independent of interaction with adrenergic influences. AII also influences other mesangial cell functions such as uptake of macromolecules from the circulation. AII also exerts effects by influencing the functional expression of renal adrenergic activity, as demonstrated by studies with renal nerve stimulation in the presence and absence of angiotensin-converting enzyme inhibitor and saralasin. Inhibition of AII activity also clearly suppresses tubuloglomerular activity and the PG response to alterations in distal tubular flow rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

An analysis of glomerular-tubular balance in the rat proximal tubule.

An analysis of glomerulo-tubular balance in the rat proximal tubule. Flow dependence of absolute proximal reabsorption (APR) or glomerulo-tubular balance (GTB) has been observed with spontaneous alterations in flow and attributed to both intraluminal and extraluminal factors. Flow dependent alterations in APR were demonstrated when 1. nephron filtration rate (SNGFR) was decreased by tubulo-glomerular feedback mechanisms by increasing late proximal tubular microperfusion rates, and 2. when SNGFR was increased by addition of [Sar1, Ala8] angiotensin II to the adjacent peritubular capillary flow. Selective reduction in early proximal tubular flow rate by pump aspiration also resulted in flow dependent reductions in APR. However, selective additions of perfusion fluids of various native and artificial constituency to the early proximal tubule did not result in flow dependent increase in APR. Conclusions. 1. GTB with both increases and decreases in SNGFR can be demonstrated at the level of the single nephron, 2. selective reductions in luminal flow rate produces parallel reductions in APR; however, 3. increases in flow rate with either artificial or native fluids of different ionic concentrations did not result in increases in APR. This lack GTB may be due to lack of parallel changes in peritubular physical factors or that APR in the S2 segment is less sensitive to increase in flow rate.

Animals↗
PubMed1986

Effects of the anaphylatoxin, C5a, on renal and glomerular hemodynamics in the rat.

The effects of intrarenal infusion of the complement-derived anaphylatoxin, C5a, upon glomerular hemodynamics were examined in the Munich-Wistar rat, a strain with glomeruli on the kidney surface. Human C5a (1.5 micrograms/min) or vehicle was infused into the left renal artery for 12 min, and glomerular capillary (PG) and Bowman's space pressures, nephron plasma flow (SNPF) afferent and efferent arteriolar protein concentrations, nephron filtration rate (SNGFR) and the glomerular ultrafiltration coefficient (LpA) determined. Human C5a infusion resulted in a reduction in SNPF due to increased efferent arteriolar resistance, and PG increased which maintained SNGFR constant. LpA was numerically lower but not significantly decreased. Infusion of porcine C5ades Arg decreased glomerular filtration rate and renal blood flow. No polymorphonuclear leukocytes were observed within glomerular capillaries of C5a infused rats, and rat leukocytes did not exhibit receptors for human C5a infused. Renal artery infusion of either human C5a or porcine C5a resulted in renal hemodynamic alterations and, as documented for human C5a, effects of C5a upon renal vascular resistance can be added to the known effect of C5a on the polymorphonuclear leukocyte.

Animals↗
PubMed1986

Can causality be determined from proximal tubular reabsorption and peritubular physical factors?

Many studies in the literature have drawn conclusions regarding the mechanism of change in absolute proximal tubular reabsorption (APR) based on steady-state measurements of proximal reabsorptive rates and the peritubular capillary. The proximal reabsorptive rate, APR, is the product of the effective reabsorptive pressure (ERP) and the peritubular capillary reabsorptive coefficient (LpAR) (APR = ERP . LpAR). The ERP is defined by the net hydrostatic and oncotic pressure gradient acting across the capillary wall from interstitium to peritubular capillary flow. The relationship APR = ERP . LpAR is predefined, and steady-state measurements do not permit determination of causality because primary changes in any variable obligate a proportional change in a second variable. As an example of the difficulties in interpretation of this type of analysis, we have examined the APR and factors contributing to ERP and LpAR before and after the administration of benzolamide, a carbonic anhydrase inhibitor, to saline-expanded Munich-Wistar rats. Alterations in peritubular capillary fluid uptake cannot always be interpreted as casual mechanisms for changes in absolute fluid reabsorption but may result from primary alterations in epithelial transport.

Absorption↗
PubMed1986

Changes in glomerular hemodynamic response to angiotensin II after subacute renal denervation in rats.

We examined the changes in glomerular hemodynamics produced by angiotensin II (AII) in both normal Munich-Wistar rats and rats which were unilaterally renal denervated (measured kidney) 4-6 d prior to the measurement periods. Measurements of glomerular dynamics were performed in a control period after plasma volume expansion and during infusion of 11 ng X 100 g body wt-1 X min-1 of AII. The glomerular hydrostatic pressure gradient increased from 38 +/- 1 to 49 +/- 1 mmHg in denervated rats compared with a lesser response in controls (from 39 +/- 1 to 45 +/- 1 mmHg, P less than 0.05). Single nephron plasma flow decreased from 213 +/- 17 to 87 +/- 4 nl X min-1 X g kidney wt (KW)-1 in denervated kidneys versus a more modest decrease in control kidneys (from 161 +/- 9 to 102 +/- 5 nl X min X gKW-1). These changes were due to a greater increase in both afferent and efferent arteriolar resistance after AII infusion in denervated compared with control kidneys. Glomerular AII receptor maximum binding was 1,196 +/- 267 fmol/mg protein in denervated kidneys compared with 612 +/- 89 fmol/mg protein (P less than 0.01) in controls with no change in receptor affinity. We conclude the subacute unilateral renal denervation results in renal vasodilation, denervation magnifies the vasoconstrictive effect of AII infusion on glomerular hemodynamics, and the observed increased response to AII after denervation is associated with increases in glomerular AII receptors.

Angiotensin II↗
PubMed1985

Effect of leukocyte depletion on glomerular dynamics during acute glomerular immune injury.

Large doses of anti-glomerular basement membrane antibody (AGBM-Ab) have been shown consistently to decrease both single nephron filtration rate (SNGFR) and the glomerular ultrafiltration coefficient (LpA) within 60 min of administration of the antibody. Both the decrease in SNGFR and LpA may be the result of infiltration of leukocytes blocking capillary loops and/or endothelial cell separation from the glomerular basement membrane through leukocyte dependent activated cytotoxic products or by mechanisms associated with leukocyte activation and infiltration. Administration of 2.5 micrograms/g body wt AGBM-Ab was performed in 10 control Munich-Wistar rats and in six Munich-Wistar rats in which 3 to 5 days prior to micropuncture experiments the rats were splenectomized and then irradiated to produce leukocyte depletion. Micropuncture measurements were performed in a condition of plasma volume expansion both prior to and after AGBM-Ab administration. In the control group, SNGFR decreased from 64 +/- 3 to 48 +/- 2 nl/min X g kidney wt after AGBM-Ab administration due to a decrease in LpA from 0.13 to 0.06 nl X sec-1 X mm Hg-1 X g kidney wt-1. This decrease in either SNGFR or LpA did not occur in the leukocyte depleted group. Linear deposits of IgG and C3 were similar in both groups. Polymorphonuclear leukocytes were significantly decreased in glomerulus from 7.4 +/- 0.7 in control vs. 0.7 +/- 0.3 in leukocyte depletion (P less than 0.01). There was no difference in glomerular dynamics between controls and leukocyte depleted rats prior to AGBM-Ab administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Functional basis for the glomerular alterations in uranyl nitrate acute renal failure.

We have examined the acute renal failure that occurs after uranyl nitrate administration in the rat and the specific effects of pretreatment of rats with angiotensin converting enzyme inhibitor (CEI), plasma volume expansion (PVE) after uranyl nitrate, and a combination of these treatments. We utilized a combination of micropuncture measurements of glomerular hemodynamics, cage studies, and histologic examination of renal tissue to evaluate the degree of acute renal failure in all groups studied. Uranyl nitrate (UN) (25 mg/kg body wt) administration caused a reduction in the nephron filtration rate (SNGFR) (39.4 +/- 1.6 to 24.8 +/- 2.9 nl X min-1 X g kidney wt-1, P less than 0.02) as a result of a major decrease in the glomerular ultrafiltration coefficient (LpA) from control values (greater than or equal to 0.085 +/- 0.008 to 0.035 +/- 0.007 nl X sec-1 X mm Hg-1 X g kidney wt-1, P less than 0.01). Treatments with CEI, PVE, and the combination of CEI and PVE in rats receiving UN restored 0.38 +/- LpA to normal values (greater than 0.061 +/- 0.009, 0.091 +/- 0.020, and 0.138 +/- 0.020 nl X sec-1 X mm Hg-1 X g kidney wt-1, respectively). Cage studies revealed that CEI treatment prevented oliguria and resulted in major volume losses and reduction in weight. However, rats died after a similar period after UN, but probably by different mechanisms. Analysis of renal ultrastructure revealed equivalent tubular damage in all experimental groups. Alterations in LpA after UN are functional in nature and are potentially preventable and reversible by a combination of treatments with CEI and PVE.

Acute Kidney Injury↗
PubMed1985

Nephroimmunopathology and pathophysiology.

Immunologic models of renal injury are useful in the study of pathophysiology. Some of these models have already been used in glomerular micropuncture studies and were shown to be approachable with the same techniques that were developed to study normal renal function. The typical decrease in the glomerular permeability coefficient found in such studies is countered by an increase in the hydrostatic pressure gradient, minimizing decreases in single nephron filtration rate. Antibody mechanisms involving either direct glomerular (and tubular) fixation of antibody or accumulation of immune complex materials provide an array of acute and chronic lesions for evaluation with relevance to the bulk of immune glomerular and tubular lesions in humans. The influences of varied and overlapping immune mediator systems are also useful areas for physiologic assessment. The tools of the renal immunopathologist may be useful to the physiologist in identifying and localizing the effects of transport systems central to renal function. The collaborative interaction of investigators skilled in immunology, pathology, and physiology is necessary to achieve optimum scientific value.

Animals↗
PubMed1985

Tubuloglomerular feedback activity in virgin and 12-day-pregnant rats.

Tubuloglomerular feedback activity was evaluated by micropuncture and microperfusion techniques in virgin and 12-day-pregnant Munich-Wistar rats. Plasma volume increases in pregnancy, which could suppress feedback activity, thus contributing to the rise in glomerular filtration rate observed in normal midterm pregnancy. Late proximal tubules were microperfused at 0, 10, 20, and 40 nl/min and the resulting filtration rate in the same nephron was evaluated. Nephron filtration rate (SNGFR) in proximal and distal tubules of other nephrons was also measured to assess the degree of activation of the tubuloglomerular feedback system and the relation of the spontaneous (normal) late proximal flow rate and SNGFR (distal tubule collections). SNGFR decreased significantly (from the 0 nl/min perfusion value) when late proximal tubules were perfused at 20 and 40 nl/min in both virgin and 12-day-pregnant rats. Tubuloglomerular feedback activity was not suppressed in pregnancy, but the relationship between SNGFR and late proximal tubule perfusion rate was reset for a higher value for SNGFR. The difference between proximal and distal SNGFR suggests that the feedback system was more activated in the virgin than in the pregnant rat. Thus, in spite of the known increases in plasma volume that occur in pregnancy, the kidney does not sense this volume expansion as a stimulus to suppress feedback activity.

Animals↗
PubMed1985

An examination of chronic angiotensin-converting enzyme inhibition in the rat.

We have examined the systemic and renal effects of 2 weeks' administration of angiotensin-converting enzyme inhibition (CEI) to both normal and chronic NaCl-depleted Munich-Wistar rats and focused particularly on the factors contributing to the significant hypotension observed during surgery and anesthesia and the response of renal glomerular hemodynamics under these conditions. At renal micropuncture, mean arterial pressure was decreased in rats receiving CEI on normal and NaCl-depleted diets (72 +/- 5 and 78 +/- 6 mm Hg, p less than 0.01) but nephron filtration rate (sngfr) was well maintained since plasma flow was not altered and glomerular capillary pressure only slightly decreased. Negative Na+ balance in NaCl-depleted CEI rats correlated with decreased awake blood pressures. Under surgery, plasma norepinephrine and epinephrine were not increased in CEI rats in spite of hypotension, and diminished adrenergic responses may contribute to systemic and renal effects observed. Nephron plasma flow and sngfr are remarkably well preserved during CEI in spite of hypotension due to marked afferent arteriolar dilation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Effect of furosemide administration on glomerular and tubular dynamics in the rat.

Furosemide, a potent diuretic, has also been shown (1) to inhibit or reduce tubuloglomerular feedback activity, (2) act as a vasodilatory agent, and (3) exhibit a modest carbonic anhydrase inhibitory effect, which could potentially reduce proximal tubule reabsorption. If furosemide can inhibit tubuloglomerular feedback as well as cause vasodilation, then glomerular filtration rate (GFR) should increase through alterations in the dynamics of glomerular ultrafiltration. The effect of acute furosemide infusion (4 mg/kg of body wt per hour) on glomerular and tubular dynamics was examined in Munich-Wistar rats by two protocols: The first allowed a 3% volume depletion (based on body wt) to occur as a result of furosemide administration (group 1); the second allowed a complete replacement of volume after furosemide administration (group 2). The results demonstrated that when volume status was maintained after furosemide administration, the nephron filtration rate remained constant (35 +/- 3 vs. 33 +/- 2 nl/min, NS) despite a twofold increase in distal flow rate (5 +/- 1 vs. 10 +/- 1 nl/min, P less than 0.01), indicating an inhibition or suppression of the tubuloglomerular feedback system. With either protocol, furosemide administration did not alter total nephron vascular resistance and nephron blood flow (190 +/- 17 vs. 200 +/- 15 ml/min); however, the afferent arteriolar resistance did decrease in rats in which volume status was maintained. Finally, with volume status maintained, we were not able to demonstrate a reduction in absolute proximal fluid reabsorption despite a 7 mm Hg increase in interstitial hydrostatic pressure (4 +/- 1 to 11 +/- 1 mm Hg, P less than 0.01) and no compensatory increase in interstitial oncotic pressure. These data indicate that tubuloglomerular feedback was inhibited but that GFR was not increased. Major changes occurred in interstitial pressures and interstitial volume after furosemide administration, but absolute proximal reabsorption remained constant.

Absorption↗
PubMed1984

A functional role for the tubuloglomerular feedback mechanism.

Ever increasing evidence exists that the tubuloglomerular feedback system exerts a major influence on overall renal function. Several examples are potentially pertinent to clinical medicine in which there is reasonable evidence that activation or suppression of tubuloglomerular feedback mechanisms contribute significantly to alterations in normal renal physiology. However, in most examples reported, the feedback mechanism is one of several influences acting in concert to determine the final nephron filtration rate, its respective determinants, and the relationship of filtration to the rate of tubular reabsorption. A more complete understanding of all the factors which influence and modify the functional role of tubuloglomerular feedback mechanisms will aid our understanding significantly and the consequent therapy of a variety of altered physiologic conditions.

Acute Kidney Injury↗
PubMed1984

Analysis of renal denervation in the hydropenic rat: interactions with angiotensin II.

Nephron filtration rate (SNGFR), its determinants, and proximal tubular reabsorption were measured in hydropenic Munich-Wistar rats with sham-operated (sham) or denervated (DNx) kidneys before and during the administration of [Sar1, Ala8]angiotensin II or SQ 14225. The glomerular ultrafiltration coefficient (LpA) was significantly lower in DNx than in sham rats (P less than 0.025). However, SNGFR was not altered due to an offsetting increment in transcapillary glomerular hydrostatic pressure (delta P) in DNx (P less than 0.005). The marked increment of delta P in DNx was due to an increase in the glomerular capillary hydrostatic pressure, secondary to decreased afferent arteriolar resistance. The infusion of angiotensin II inhibitors to denervated kidneys completely normalized LpA but did not alter sham values. SQ 14225 but not [Sar1, Ala8]angiotensin II infusion provided a nephron plasma flow-dependent increase in SNGFR, secondary to a striking reduction in both glomerular vascular resistances. Endogenous angiotensin II activity may be enhanced by renal denervation, and angiotensin II acts to reduce LpA in this condition and may modulate the final level of renal vascular resistances after acute renal denervation.

Absorption↗