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R C Blantz

Publications and source records attributed to R C Blantz.

At least 91 records · Page 5Linked to original sources
PubMed1990

Adrenergic influences and interactions with angiotensin II.

Increasing evidence indicates the existence of a complex interplay between the angiotensin and adrenergic nervous systems within the kidney. Since both of these vasoconstrictor systems are integrally involved in the maintenance of systemic blood pressure and fluid and electrolyte homeostasis, it is not surprising that each might influence the other vis-a-vis their mutual capacity to alter the physiologic determinants of glomerular filtration.

Angiotensin II↗
PubMed1989

Early events in ischemic renal failure in the rat: effects of antioxidant therapy.

Renal ischemia followed by two hours of reperfusion produces a complex form of acute renal failure characterized by a reduction in nephron filtration rate (SNGFR) and moderate proximal tubular damage. We have examined glomerular hemodynamics, SNGFR and histologic changes after renal ischemia and two hours of reperfusion in untreated (I) rats and rats pretreated with the antioxidant, probucol (IP). SNGFR decreased significantly by 47% in I rats. Reduction in SNGFR was primarily the result of a major decrease in the glomerular capillary hydrostatic pressure gradient, delta P, and a decrease in nephron plasma flow (SNPF). The glomerular ultrafiltration coefficient remained equal to control valves. In IP rats SNGFR was improved to values 89% of control rats due to higher values of delta P and SNPF. Histologic evidence of modest damage to cells of the proximal tubule was equal in both untreated and probucol treated ischemic animals. These studies demonstrate that: (a) primary reductions in nephron filtration rate at the glomerulus result from decreases in delta P and nephron plasma flow; b) pretreatment with the antioxidant, probucol, increases nephron plasma flow and SNGFR, and maintains more normal values for delta P; and c) tubular damage was equivalent in I and IP rats in spite of differences in SNGFR.

Animals↗
PubMed1989

A single nephron model of acute tubular injury: role of tubuloglomerular feedback.

A single nephron model of nephrotoxic tubular injury was established to examine the mechanism whereby acute tubular damage contributes to reductions in nephron filtration rate (SNGFR). Acute microperfusion of 0.5 ng of uranyl nitrate (UN) into the early proximal tubule produced a significant reduction (16 to 30%) in SNGFR measured in both distal and proximal tubules of the same nephron and a decrease in absolute proximal reabsorption. Microperfused inulin was retained in the tubule suggesting this finding reflected a true reduction in SNGFR. Concurrent infusion of high dose furosemide (2 x 10(-4)M) and bumetanide (2 x 10(-5) M), but not low dose furosemide (2 x 10(-5) M), prevented the UN induced reduction in SNGFR. High dose furosemide begun after UN perfusion also prevented reduction in SNGFR. Continuous direct measurement of glomerular capillary hydrostatic pressure revealed no change. Distal intratubular Na+ and Cl- concentration increased significantly after UN perfusion. Activation of tubuloglomerular feedback mechanisms best explains the reduction in glomerular ultrafiltration that is characteristic of nephrotoxic forms of tubular injury.

Acute Kidney Injury↗
PubMed1989

Glomerular hemodynamics in pathophysiologic conditions.

Under normal conditions glomerular blood flow and glomerular capillary hydrostatic pressure and hydrostatic pressure gradient are regulated within a narrow range in spite of variations in volume status and blood pressure. Glomerular ultrafiltration rate is normally regulated by the hydrostatic pressure gradient, the systemic oncotic pressure, the rate of nephron plasma flow and the glomerular ultrafiltration coefficient. Although the process of glomerular ultrafiltration is driven by the hydrostatic pressure gradient (delta P), regulation of nephron filtration rate (SNGFR) is not mediated by changes in hydrostatic pressure and the correlation between SNGFR and delta P is very poor. There are certain clinical experimental models in which the glomerular capillary hydrostatic pressure gradient is elevated. These models have been: (1) subtotal nephrectomy model, a model of reduced renal mass, (2) glomerular immune induced injury or glomerulonephritis, (3) most models of systemic hypertension, and (4) certain stages of experimental diabetes mellitus, but the mechanisms vary among the conditions. In most of these clinical models the increase in delta P is associated with a reduction in the glomerular ultrafiltration coefficient. It is also clear that superimposition of hypertension upon models of glomerular immune injury and radical subtotal nephrectomy cause progression of renal dysfunction and glomerulosclerosis. One of the contributing factors to this progression appears to be the elevation in glomerular capillary hydrostatic pressure and pressure gradient. However, other factors have been suggested to play a significant role, such as compensatory hypertrophy and possibly the neurohumoral environment. Therapy of systemic hypertension and administration of cardiovascular drugs which alter glomerular capillary hydrostatic pressure may then modify the rate of progresswion of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of tertatolol on glomerular hemodynamics in the normal Munich-Wistar rat.

Administration of beta-blockers is frequently associated with decreases in both renal plasma flow and glomerular filtration rate (GFR). Tertatolol, a new non-selective beta-blocker, has demonstrated similar systemic effects to other conventional beta-blockers, but tertatolol produces increases in both renal plasma flow and glomerular filtration rate. To evaluate the renal hemodynamic mechanism responsible for the increase in GFR, micropuncture experiments were performed in normal Munich-Wistar rats. Intravenous injection of tertatolol produced a significant increase in GFR and urinary sodium excretion in spite of a decrease in systemic blood pressure. Single nephron glomerular filtration rate was significantly increased due to an increase in single nephron plasma flow related to parallel afferent and efferent arteriolar dilatation. No significant changes in glomerular hydrostatic pressure, transcapillary hydrostatic pressure gradient or the ultrafiltration coefficient were demonstrated with tertatolol. The capacity of tertatolol to increase glomerular filtration rate and to promote sodium excretion without modifying critical glomerular pressures makes this agent a highly attractive antihypertensive drug.

Adrenergic beta-Antagonists↗
PubMed1989

Tubuloglomerular feedback activity after glomerular immune injury.

Tubuloglomerular feedback responses were examined in control euvolemic and glomerulonephritic rats 4 wk after administration of antiglomerular basement membrane antibody (AGBM). Single-nephron glomerular filtration rate (SNGFR) was reduced approximately 30% in AGBM rats. Tubuloglomerular feedback responses were also tested with both artificial and native tubular fluid. SNGFR was evaluated at 0, 10, 20, 30, and 40 nl/min. Tubuloglomerular feedback response was present in both control and AGBM rats, although there was a shift in turning point or perfusion rate down and leftward at which SNGFR decreased in the AGBM rats. No difference in tubuloglomerular feedback responses was observed between artificial and native tubular fluids. In this model of moderate glomerulonephritis, tubuloglomerular feedback activity appears to be appropriate and intact, and the composition of the fluid entering the loop of Henle does not appear to determine or to be a condition for the presence or absence of tubuloglomerular feedback activity.

Animals↗
PubMed1989

Effects of beta 1-adrenergic blockade on glomerular dynamics and angiotensin II response.

Adrenergic activity regulates renal function by several mechanisms. Renal nerves not only exert vasoconstrictor functions but also may influence glomerular hemodynamics by beta-adrenergic activity, especially via the effects on renin angiotensin activity. Little is known of the specific glomerular hemodynamic alterations resulting from beta 1-adrenergic blockade. Current studies examined the effects of 4-6 days of treatment with atenolol (50 mg/kg), a beta 1-selective adrenergic antagonist, on glomerular hemodynamics in plasma volume-expanded Munich-Wistar rats. Atenolol treatment reduced blood pressure both in the awake state and during micropuncture. This reduction in blood pressure contributed to a decrease in nephron filtration rate (48 +/- 1 in untreated rats vs. 40 +/- 1 nl.min-1.g kidney wt-1 in the atenolol-treated group, P less than 0.05) by reduction in nephron plasma flow (182 +/- 2 vs. 154 +/- 4 nl.min-1.g kidney wt-1 in the atenolol-treated rats). No other determinant of glomerular ultrafiltration was influenced by atenolol treatment. Since beta 1-adrenergic blockade may influence the generation of angiotensin II, the response to angiotensin II infusion was assessed and found not to differ from control untreated animals. These studies demonstrate that beta 1-receptor blockade reduced nephron filtration rate by decreasing mean arterial blood pressure and nephron plasma flow without significant modifications in vascular resistance and the glomerular hydrostatic pressure gradient.

Angiotensin II↗
PubMed1989

Effects of beta-adrenergic stimulation with isoproterenol on glomerular hemodynamics.

To evaluate the contribution of beta 1-2-adrenergic receptor stimulation to the regulation of single-nephron glomerular filtration rate (SNGFR), we examined by micropuncture techniques the effects of systemic and intrarenal infusion of isoproterenol on glomerular hemodynamics in plasma volume-expanded Munich-Wistar rats. Isoproterenol infused systemically was consistently associated with an elevation in glomerular capillary hydrostatic pressure difference (delta P) from 44.2 +/- 1.2 to 50.1 +/- 1.3 mmHg, P less than 0.01, the consequence of a 5.9-mmHg fall in Bowman's space hydrostatic pressure, P less than 0.005. The potentially beneficial effect of increased delta P on SNGFR was overcome by a 40% reduction in the glomerular ultrafiltration coefficient (LpA) from 0.043 +/- 0.003 to 0.026 +/- 0.003 nl.s-1.mmHg-1.g kidney wt-1, P less than 0.005, with a net effect of a modest 13% decline in SNGFR, P less than 0.01. In contrast, the intrarenal infusion of isoproterenol did not modify glomerular hemodynamics. Suppression of angiotensin II activity eliminated the influences of systemic isoproterenol infusion on LpA and delta P, the latter was the consequence of lower efferent arteriolar resistance. The findings suggest that systemic infusion of a beta 1-2-adrenergic agonist results in a decrease in LpA via angiotensin II effects and exerts a vasodilatory action on postglomerular vessels during angiotensin II inhibition.

Angiotensin II↗
PubMed1989

Functional effects on glomerular hemodynamics of short-term chronic cyclosporine in male rats.

We evaluated the effects of chronic cyclosporine (CsA) administration on the determinants of nephron filtration rate (SNGFR) using micropuncture techniques (mp) in male Munich-Wistar rats. Animals received CsA (30 mg/kg SQ) in olive oil daily for 8 d before mp. Controls (PFC) were pair fed. SNGFR, glomerular capillary hydrostatic pressure gradient (delta P), nephron plasma flow (SNPF), plasma protein oncotic pressure (pi A), and glomerular ultrafiltration coefficient (LpA) were quantitated in each experiment. CsA was associated with a lower SNGFR due to decreases in SNPF and a major reduction in delta P but no decrease in LpA. Plasma volume expansion (PVE) caused SNGFR, delta P, and SNPF to increase in both CsA and PFC without eliminating the differences between CsA and PFC. CsA/PVE rats responded normally to angiotensin II (AII) infusion indicating that the low delta P associated with CsA is not due to unresponsiveness to AII. Prior renal denervation caused SNGFR and SNPF to increase in CsA-treated animals but failed to alter the reduction in glomerular capillary pressure after CsA or to eliminate the glomerular hemodynamic differences between treated animals and pair-fed controls. This constellation of glomerular hemodynamic abnormalities suggests that the renal effect of short-term chronic CsA administration is mediated primarily by a reduction in the afferent effective filtration pressure resulting from an imbalance between pre- and postglomerular vascular resistances.

Angiotensin II↗
PubMed1988

Role of angiotensin II in experimental membranous nephropathy.

Glomerular hemodynamics measurements in rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)] have demonstrated that the appearance of proteinuria 5 days after administration of anti-Fx1A antibody is temporally related to changes in the glomerular ultrafiltration coefficient (LpA). Previous studies in other models of glomerular injury have suggested a significant role for angiotensin II (ANG II) in the glomerular hemodynamic abnormalities. To evaluate the possible role of ANG II in the LpA decrease, converting enzyme inhibitor (CEI) was administered acutely or chronically (5 days before and after induction of PHN) to rats with PHN. Acute ANG II blockade produced a fall in mean arterial pressure (MAP), single-nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption (APR), single-nephron plasma flow, single-nephron blood flow, and glomerular capillary hydrostatic pressure (PG); however, no changes in LpA were detected. Chronic administration of CEI (MK421, 5 mg.kg-1.day-1) in the drinking water was associated with a fall in MAP; however, both SNGFR and APR increased. PG and the transcapillary hydrostatic pressure gradient were unchanged, and LpA remained depressed. These results suggest that reduction of LpA in rats with PHN is ANG II independent and that other mechanisms are required to explain these changes in glomerular hemodynamics.

Angiotensin II↗
PubMed1988

Tubuloglomerular feedback.

Increasing evidence is accumulating that the tubuloglomerular feedback system exercises significant control over the glomerular filtration rate. We present our current understanding of the mechanisms underlying the operation of the TGF system and discuss several situations applicable to clinical medicine where altered TGF responses are likely to be manifested as perceivable changes in overall renal function.

Feedback↗
PubMed1988

Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction.

The effects of antioxidant therapy with probucol were evaluated in rats subjected to 1 h renal ischemia and to 24 h reperfusion. Probucol exerted significant antioxidant effects in renal cortical tubules in vitro when exposed to a catalase-resistant oxidant. At 24 h probucol treatment (IP) improved single nephron glomerular filtration rate (SNGFR) (28.1 +/- 3.3 nl/min) in comparison to untreated ischemic (I) rats (15.2 +/- 3.0), primarily as a result of improving SNGFR in a population of low SNGFR, low flow and/or obstructed nephrons. However, absolute proximal reabsorption remained abnormally low in IP rats at 24 h (5.9 +/- 0.8 nl/min), and cell necrosis was greater than in I rats. Kidney GFR remained low in IP rats due to extensive tubular backleak of inulin measured by microinjection studies. Evaluations after 2 h of reperfusion revealed a higher SNGFR in IP (36 +/- 3.1 nl/min) than I rats (20.8 +/- 2.7 nl/min). Absolute proximal reabsorption was essentially normal (11.6 +/- 1.3 nl/min) in IP rats, which was higher than IP rats at 24 h and the concurrent I rats. Administration of the lipophilic antioxidant, probucol, increased SNGFR and proximal tubular reabsorption within 2 h after ischemic renal failure. Although SNGFR remained higher than I rats at 24 h, absolute reabsorption fell below normal levels and tubular necrosis was more extensive in IP rats. Early improvement in nephron filtration with antioxidants may increase load dependent metabolic demand upon tubules and increase the extent of damage and transport dysfunction.

Acute Kidney Injury↗
PubMed1988

Sexual differences in glomerular ultrafiltration: effect of androgen administration in ovariectomized rats.

The glomerular ultrafiltration rate varies as a function of age and sex. To further elucidate the basis for the sexual difference, an androgen [Deca-Durabolin (DECA)] was administered to female ovariectomized rats, and glomerular hemodynamics were evaluated by renal micropuncture after 6 and 16 weeks of therapy. Results were compared to those in control ovariectomized female rats injected with vehicle. Therapy did not produce significant differences in body weight, but kidney size was modestly increased in DECA-treated rats at 6 weeks (0.68 +/- 0.03 vs. 0.86 +/- 0.03 g wet weight; P less than 0.05); at 16 weeks major differences in renal size were documented (0.69 +/- 0.03 vs. 1.18 +/- 0.05 g wet weight; P less than 0.01). The increase in size was primarily due to tubular hypertrophy, with more modest increases in glomerular size. After 6 weeks of therapy, the single nephron glomerular filtration rate (SNGFR) was increased in DECA-treated ovariectomized rats (24.8 +/- 1.0 vs. 32.9 +/- 1.1 nl/min; P less than 0.01). Whole kidney glomerular filtration rate also rose in proportion to increases in kidney size. The greater SNGFR was attributed to higher rates of nephron plasma flow and a numerical increase in the glomerular ultrafiltration coefficient. However, after 16 weeks of androgen therapy, in spite of marked renal hypertrophy, SNGFR did not further rise in proportion to renal size, and the rate of nephron plasma flow and the glomerular ultrafiltration coefficient actually fell relative to those in control untreated rats. Light microscopic evaluation of renal tissue revealed no abnormalities in DECA-treated rats. Thus, 6-week androgen therapy to ovariectomized female rats increased both glomerular ultrafiltration rates and renal size. However, with prolonged administration a glomerular dysfunction may have ensued whereby glomerular ultrafiltration was dissociated from increases in renal size.

Androgens↗
PubMed1988

An evaluation of the role of complement depletion in experimental membranous nephropathy in the rat.

Passive Heymann nephritis (PHN), a model of experimental membranous nephropathy produced by the administration of anti-Fx1A antibody, was studied by micropuncture measurement of glomerular hemodynamics and by assessment of immunologic and morphologic findings. The effect of complement depletion on these parameters was evaluated by administering cobra venom factor. Five days after administration of anti-Fx1A Ab to PHN controls, abnormal proteinuria developed and nephron filtration rate decreased due to modest reductions in nephron plasma flow and major reductions (75%) in the glomerular ultrafiltration coefficient. Glomerular capillary hydrostatic pressure gradient was significantly increased and decreased tubular reabsorption was also evident. Complement depletion prevented abnormal proteinuria and normalized tubular reabsorption and some of the glomerular hemodynamic parameters (nephron plasma flow and glomerular capillary hydrostatic pressure gradient). Values for the glomerular ultrafiltration coefficient, a possible index of membrane damage, were significantly improved (100%) after cobra venom factor treatment, although they remained below normal values. Only minimal differences in glomerular and epithelial cell morphology and appearance of electron-dense material were noted between PHN and PHN + cobra venom factor. These data suggest therefore that both complement-dependent and independent mechanisms contribute to explain the changes in nephron filtration and reabsorption that occur in this model of experimental membranous nephropathy.

Animals↗
PubMed1987

Acute renal failure: the glomerular and tubular connection.

Acute renal failure (ARF) is a common clinical entity which results from multiple causes. Experimental models in animals have duplicated many of the clinical syndromes which can be classified into (1) ARF due to increased filtered load of endogenous and exogenous materials, (2) ARF associated with exogenous nephrotoxins and (3) ischemic forms of renal failure secondary to hypoperfusion and hypotension. The mechanisms leading to the reduction in GFR are multiple and the alterations in determinants of nephron filtration rate and degree of tubular backleak and obstruction are described for each of these subtypes of experimental ARF. The specific mechanisms whereby tubular damage translates into a reduction in GFR in ARF are discussed for each subtype of ARF. Tubular damage can often be dissociated from the reduction in GFR, possibly by inhibiting tubuloglomerular feedback responses, but such increases in GFR and nephron filtration rate are not necessarily beneficial to the organism because of potential volume depletion and the risk of magnifying further tubular damage. Information on the physiologic role of tubuloglomerular feedback activity in ARF is provided and supports the concept that feedback induced reductions in GFR after tubular injury may preserve extracellular volume and minimize further tubular damage. Reductions in tubular metabolic work appears to prevent and ameliorate further tubular injury after the initial insult. The mechanisms which associate changes in GFR and tubular damage can now be described, and therapies which improve GFR without correcting the tubular damage may compound the clinical problem and increase renal damage.

Acute Kidney Injury↗
PubMed1987

An evaluation of the development of experimental membranous nephropathy.

Heymann nephritis is a rat model of glomerulonephritis with morphologic manifestations of human membranous nephropathy. This model is generated by immunizing rats with Fx1A antigen. Passive Heymann's nephritis (PHN) can be produced by the administration of anti-Fx1A antibody (anti-Fx1A Ab) (with abnormal proteinuria appearing in 5 days). Studies were designed to examine the evolution of temporal changes in protein excretion, the glomerular ultrafiltration coefficient (LpA) and morphology of glomerular capillary three and five days after induction of PHN. Glomerular hemodynamic evaluation by micropuncture in euvolemic rats with PHN revealed normal values for nephron filtration rate (SNGFR), LpA and the glomerular hydrostatic pressure gradient (delta P) at day three, but by day five the whole kidney GFR and SNGFR were decreased, delta P increased and LpA significantly reduced. Glomerular binding of anti-Fx1A Ab increased from 38 micrograms/7.6 X 10(4) glomeruli on day three to 52 micrograms on day five. Immune complex deposits evaluated by immunofluorescence and electron microscopy appeared larger and were better defined on day five than on day three. Epithelial foot process fusion was more extensive on day five than day three. The onset of increased proteinuria correlated temporally with a reduction in LpA on day five, which in turn correlated with increased antibody binding, immune deposit accumulation and fusion of epithelial cell foot processes.

Animals↗
PubMed1987

The influence of concomitant experimental hypertension and glomerulonephritis.

Utilizing the two kidney-one clip Goldblatt model (CH), we have examined the influence of hypertension upon the course of antiglomerular basement membrane antibody-induced glomerulonephritis (GN) over a period of 10 to 14 weeks after induction of CH and GN, utilizing evaluations in the awake rat by renal micropuncture of the unclipped kidney and morphologic analysis (control [C], GN, CH, and GN+CH). Metabolic studies revealed that GN and GN+CH rats developed proteinuria, elevations in serum creatinine and blood pressure (P less than 0.05). GN+CH resulted in significant reductions in two kidney glomerular filtration rate (GFR) below values in C, and GFR in the unclipped kidney was markedly reduced when compared to CH. The glomerular capillary hydrostatic pressure and the pressure gradient( (delta P) were elevated approximately 4 to 5 mm Hg in GN and CH rats and 6 mm Hg above GN and CH values in the GN+CH rats. The glomerular ultrafiltration coefficient (LpA) was reduced to approximately 40% of C in both GN and GN+CH in spite of further increases in delta P. Surface nephron filtration rate was similar in all groups, suggesting glomerular dysfunction was primarily in nephrons below the surface in GN+CH. Morphologic evaluation revealed that GN+CH exhibited a combination of diffuse and focally sclerotic lesions characteristic of GN and CH, respectively. Documented further increases in PG did not worsen glomerular morphology, but kidney GFR did decrease. Hypertension induced deterioration of glomerular function in nephrons below the surface was not associated with marked morphologic deterioration, but a combination of the characteristics of GN and CH.

Animals↗