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R C Blantz

Publications and source records attributed to R C Blantz.

At least 73 records · Page 4Linked to original sources
PubMed1992

Nitric oxide and angiotensin II. Glomerular and tubular interaction in the rat.

Nitric oxide (NO) has been proposed to modulate the renal response to protein as well as basal renal hemodynamics. We investigated whether NO and angiotensin II (AII) interact to control glomerular hemodynamics and absolute proximal tubular reabsorption (APR) during glycine infusion and in unstimulated conditions. In control rats, glycine increased single nephron GFR and plasma flow with no change in APR. The NO synthase blocker, NG-monomethyl L-arginine (LNMMA), abolished the vasodilatory response to glycine, possibly through activation of tubuloglomerular feedback due to a decrease in APR produced by LNMMA + glycine. Pretreatment with an AII receptor antagonist, DuP 753, normalized the response to glycine at both glomerular and tubular levels. In unstimulated conditions, LNMMA produced glomerular arteriolar vasoconstriction, decreased the glomerular ultrafiltration coefficient, and reduced single nephron GFR. These changes were associated with a striking decrease in APR. DuP 753 prevented both glomerular and tubular changes induced by LNMMA. In conclusion, NO represents a physiological antagonist of AII at both the glomerulus and tubule in both the basal state and during glycine infusion; and inhibition of NO apparently enhances or uncovers the inhibitory effect of AII on proximal reabsorption.

Angiotensin II↗
PubMed1992

Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat.

The hypothesis that renal alpha 2 adrenoceptors influence nephron filtration rate (SNGFR) via interaction with angiotensin II (AII) was tested by renal micropuncture. The physical determinants of SNGFR were assessed in adult male Munich Wistar rats 5-7 d after ipsilateral surgical renal denervation (DNX). DNX was performed to isolate inhibitory central and presynaptic alpha 2 adrenoceptors from end-organ receptors within the kidney. Two experimental protocols were employed: one to test whether prior AII receptor blockade with saralasin would alter the glomerular hemodynamic response to alpha 2 adrenoceptor stimulation with the selective agonist B-HT 933 under euvolemic conditions, and the other to test whether B-HT 933 would alter the response to exogenous AII under conditions of plasma volume expansion. In euvolemic rats, B-HT 933 caused SNGFR to decline as the result of a decrease in glomerular ultrafiltration coefficient (LpA), an effect that was blocked by saralasin. After plasma volume expansion, B-HT 933 showed no primary effect on LpA but heightened the response of arterial blood pressure, glomerular transcapillary pressure gradient, and LpA to AII. The parallel results of these converse experiments suggest a complementary interaction between renal alpha 2-adrenergic and AII systems in the control of LpA.

Adrenergic alpha-Antagonists↗
PubMed1992

Renal functional reserve in the early stage of experimental diabetes.

The role of renal functional reserve (RFR; increase in plasma flow and glomerular filtration rate in response to protein loading) as an indicator of increased glomerular hydrostatic pressure and flow was evaluated in recent-onset poorly controlled diabetic rats. Streptozocin-induced diabetic (STZ-D) rats were studied with micropuncture (MP) technique after 10-15 days of diabetes (daily blood glucose level 15.3-18 mmol). We also studied STZ-D rats treated with the converting-enzyme inhibitor (CEI) enalapril or the angiotensin II (ANG II) receptor antagonist DuP 753 (DuP) for 3 days before MP. Nondiabetic rats (NOR) served as controls. Glomerular hemodynamics and proximal tubular reabsorption were measured in the control period and during intravenous glycine infusion. In NOR rats, glycine increased single-nephron plasma flow (SNPF) and single-nephron glomerular filtration rate (SNGFR). Although STZ-D rats did not exhibit hyperfiltration, SNGFR and SNPF were not modified by glycine, defining loss of RFR. CEI rats responded to glycine with an increase in SNGFR due to a rise in SNPF and a rise in the ultrafiltration coefficient. Interestingly, loss of RFR in STZ-D rats was associated with a decrease in absolute proximal reabsorption. The decrease in absolute proximal reabsorption was corrected by both CEI and DuP, although glomerular vasodilation was restored only in the CEI group. In conclusion, at the early stage of diabetes mellitus, loss of RFR does not detect hyperfiltration, but rather the presence of a tubular alteration probably dependent on ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1991

Disassociation between glomerular hyperfiltration and extracellular volume in diabetic rats.

The relationship of the development of glomerular hyperfiltration in diabetes to changes in extracellular fluid volume has not been previously examined. To accomplish this task, male Wistar rats were chronically cannulated in the bladder, femoral artery and vein. Control measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), extracellular fluid volume (ECF), and urinary sodium excretion were performed on two separate days prior to infusion of streptozotocin (65 mg/kg body wt i.v.). After infusion of streptozotocin, the IDDM rats were separated into two groups: untreated IDDM group of rats and IDDM rats treated with insulin at doses sufficient to normalize blood glucose (Ultralente, 2 to 8 IU/day). A third group of normal non-diabetic rats served as time controls. Measurements of renal function occurred at 1, 4, 7, 11, and 15 days after infusion of streptozotocin. Blood glucose in the non-diabetic measurement period averaged 137 +/- 30 mg/dl and increased from 412 +/- 55 after 24 hours in the untreated diabetic rats to 533 +/- 33 mg/dl after 15 days of IDDM. The time controls and the insulin-treated diabetic rats did not differ in blood glucose values at the time measurements were performed. Glomerular filtration rate increased from 1.0 +/- 0.1 to 1.7 +/- 0.1 ml/min/100 g body wt by day 15 in the untreated diabetic rats with significant increases in GFR within 24 hours. GFR of both time controls and the insulin-treated IDDM rats did not significantly vary during the time of the study. The increase in GFR in the untreated IDDM group was associated with a concomitant increase in RPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Renal functional reserve in treated and untreated hypertensive rats.

Renal functional reserve (renal response to protein loading, RFR) has been suggested as a method to verify the presence of hyperfiltration. This study was designed to evaluate the role of RFR as an indicator of increased glomerular capillary hydrostatic pressure in short-term treated and untreated rats with two-kidney, one-clip Goldblatt hypertension. One month after placing a silver clip, micropuncture studies were performed on the unclipped kidney. Normal rats and three groups of clipped rats [untreated group (HYP), a group treated with captopril (CEI) and a group treated with verapamil (VER) 5 days before the micropuncture studies] were studied. Glomerular hemodynamics and proximal tubular reabsorption were measured in control period and during intravenous administration of glycine (G). In normal rats, G produced afferent and efferent dilation, increases in single nephron plasma flow (SNPF) and single nephron glomerular filtration rate (SNGFR) of 24%. Systemic hypertension in HYP rats was associated with increases in transcapillary pressure gradient (delta P) and SNGFR. In this hyperfiltration state, infusion of G did not modify SNGFR of SNPF defining loss of RFR. The antihypertensive treatment was equally effective in normalizing MAP and delta P in CEI and VER, but only CEI rats responded to G with a 20% increase in SNGFR due to an increase in delta P. The most striking findings were that loss of RFR in both HYP and VER rats was associated with a significant decrease in absolute and proximal fractional reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of mesangial cell lysis and proliferation on glomerular hemodynamics in the rat.

To elucidate an involvement of mesangial cells in the regulation of glomerular hemodynamics, renal micropuncture techniques and glomerular morphometry were employed in Munich-Wistar rats with mesangial cell lytic or proliferative lesions induced by administration of an antibody reactive with Thy-1.1-like antigens on the mesangial cell surface. The antibody-induced mesangial cell lysis at day 1 resulted in a significant decrease in glomerular ultrafiltration coefficient, leading to reduction in single nephron glomerular filtration rate (SNGFR) in spite of a significant increase in both glomerular hydrostatic pressure and single nephron plasma flow (SNPF). During the antibody-induced proliferative lesion at day 6, glomerular ultrafiltration coefficient and SNGFR remained reduced; however, SNPF was now decreased. Morphometric analysis showed the enlargement of capillary luminal volume and the development of new open space in the mesangium accessible for blood flow in the mesangial cell-lytic glomeruli at day 1. An increase in mesangial cell volume was found in the proliferative glomeruli at day 6. The total area of peripheral glomerular basement membrane, presumed as the probable filtration area, was unchanged in these glomeruli. These results indicate that mesangial lesions decrease glomerular ultrafiltration coefficient, and suggest that mesangial cells participate in regulation of glomerular filtration rate.

Animals↗
PubMed1991

Effects of beta-adrenergic blockade on the glomerular and tubular response to acute renal denervation.

Using micropuncture techniques in euvolemic adult male Munich-Wistar rats, we assessed the functional role of renal beta-adrenoceptors in mediating neural control of glomerular filtration and proximal tubular reabsorption. The determinants of nephron filtration and rate of proximal tubular reabsorption were measured in two groups of animals before and after acute surgical renal denervation (DNX). Group A animals (n = 6) were pretreated with the beta-adrenoceptor antagonist propranolol (25 mg/kg body weight per day for 4-6 days). Group B animals (n = 7) served as non-beta-blocked controls. Acute renal DNX resulted in no significant change in nephron filtration rate or any of its determinants in either group. Acute DNX caused similar decrements in the rate of fluid reabsorption from the proximal convoluted tubule of beta-blocked and control rats. Loop of Henle fluid reabsorption did not appear to be affected by DNX in either group. Because the effect of denervation on proximal tubular reabsorption was not conditioned by prior beta-blockade, the beta-adrenoceptors present within the proximal convoluted tubule do not appear to be the primary mediators of the adrenergic influence on fluid transport in that segment of the nephron.

Absorption↗
PubMed1991

Tubuloglomerular feedback responses to acute contralateral nephrectomy.

After unilateral nephrectomy adaptive events must occur in the remaining kidney within the first 12-14 h in anticipation of an increase in glomerular filtration rate (GFR) and eventual renal hypertrophy. Utilizing micropuncture and microperfusion techniques in the rat, we have examined tubuloglomerular feedback (TGF) and single-nephron GFR (SNGFR) responses while the late proximal tubule was microperfused [late proximal tubule flow (VLP)] from 0 to 40 nl/min in 10 nl/min intervals at 2-4 and 12 h after contralateral nephrectomy. Urinary excretion increased, but SNGFR derived from distal collections was reduced, and early distal flow rate remained constant 2-4 h after nephrectomy. The operating point was shifted, suggesting activation of TGF. The turning point half-maximal activity (V1/2) and slope were not statistically different when all nephron data were submitted to a curve-fitting procedure, but group mean data suggested a quantitatively lower V1/2 and steeper slope of the TGF profile. Twelve to fourteen hours after contralateral nephrectomy, values for SNGFR at all microperfusion rates were increased, as were late proximal and early distal flow rates. The values for V1/2 and slope of TGF were not statistically different from control values. We conclude that TGF activity and sensitivity are not suppressed at 2 and 12 h after nephrectomy. Increased urinary excretion does not require TGF alterations. Changes in TGF may be adaptive to increases in SNGFR and may not be causal to the increase in filtration rate after nephrectomy.

Animals↗
PubMed1991

Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat.

This study was undertaken to investigate the mechanisms by which an infusion of recombinant human insulin-like growth factor I (rhIGF-I) increases GFR and renal plasma flow (RPF) in rats. Glomerular micropuncture studies were carried out in 14 nonstarved Munich Wistar rats and in 12 rats deprived of food for 60-72 h. Animals were given an intravenous injection and infusion of either rhIGF-I or vehicle. In both nonstarved and starved animals, the IGF-I injection and infusion increased the serum IGF-I levels, left kidney GFR, single nephron glomerular filtration rate (SNGFR), single nephron blood flow rate (SNBF), and single nephron plasma flow rate (SNPF). The increase in SNPF and SNGFR was in part due to a fall in efferent arteriolar resistance (RE); there was a tendency, not significant, for afferent arteriolar resistance (RA) to fall in comparison to controls. The increase in SNGFR was partly caused by a rise in SNPF but was primarily due to an increase in glomerular ultrafiltration coefficient (LpA) to twice the control values. The increase in LpA resulted in an increase in SNGFR because the rats operated at ultrafiltration pressure disequilibrium. Control starved as compared with nonstarved rats had lower SNGFR, SNBF, and SNPF. This reduction was due to a tendency, not significant, for both RA and RE to be higher. Decreased SNGFR in food-deprived rats resulted from a reduced SNPF, a lower glomerular transcapillary hydrostatic pressure difference (delta P), and possibly a somewhat reduced LpA. These data indicate that IGF-I increases SNGFR, SNPF, and SNBF primarily by increasing LpA and also by decreasing RE without affecting delta P. Short-term starvation lowers SNGFR, SNPF, and SNBF primarily by decreasing delta P and possibly by lowering LpA and increasing RA and RE. IGF-I reverses some of the glomerular hemodynamic effects of short-term food deprivation.

Animals↗
PubMed1991

Tubuloglomerular feedback activity after acute reductions in renal mass.

Removal of one kidney results in prompt increases in urinary excretion of NaCl and water from the remaining kidney, followed rather soon thereafter by increases in glomerular filtration rate (GFR). At 12-15 h and 24 h after contralateral nephrectomy, the single nephron filtration rate (SNGFR) is increased, accompanied by parallel increases in absolute proximal tubular reabsorption, late proximal tubular and early distal tubular flow rates, suggesting that these events might be critical to the increased urinary excretion. However, micropuncture studies 2-4 h after contralateral nephrectomy demonstrate that increased SNGFR and even increased distal tubular flow rates are not requirements for augmented urinary excretion, suggesting that decreased tubular reabsorption in the most distal nephron segments causes the increase in urinary excretion. Analysis of TGF profiles by stop-flow pressure response at 2-4 h after contralateral nephrectomy have suggested suppression of TGF as assessed by a rightward shift in the turning point with increasing late proximal tubular perfusion. However, our studies have examined SNGFR responses and shown no suppression of TGF profiles but a downward shift in the operating point, suggesting activation of TGF and a modest reduction in SNGFR, determined from distal tubular collections. Although SNGFR was increased at all late proximal perfusion rates 12 h after nephrectomy, the turning point (V 1/2) was not altered. TGF profiles are not suppressed within 12 h after nephrectomy while SNGFR is increased. Suppression of TGF does not cause the increase in SNGFR after nephrectomy and TGF activity is maintained and adapts to increases in SNGFR caused by TGF-independent mechanisms.

Animals↗
PubMed1990

Physiologic adaptations of the tubuloglomerular feedback system.

Knowledge of the existence of a tubuloglomerular feedback system has been available for many years. Only recently, however, have tenable hypotheses and supporting experimental data become available which have served to provide details regarding the complex inner workings of this system. The facility for examining this integrated physiologic network has derived, in large part, from the routine ability to perform in vivo micropuncture. We anticipate that further advances in this field will hinge on the development of additional experimental techniques to allow cellular biologic aspects of the system to be closely monitored in situ.

Adaptation, Physiological↗
PubMed1990

Glomerular hemodynamic alterations during renal nerve stimulation in rats on high- and low-salt diets.

Renal adrenergic nerve activity exerts a major influence on glomerular hemodynamics and tubular fluid reabsorption. Modulation of the functional expression of adrenergic activity in the kidney can be mediated, in part, by the renin-angiotensin system and by prostanoid activity. Alterations in dietary salt intake have been previously shown to modify the activity of various vasoactive systems, including angiotensin and prostaglandin activity and thereby have a potential of modifying the glomerular hemodynamic response to a given renal adrenergic stimulus. Munich-Wistar rats were fed either a high-, low-, or normal salt diet for 2 wk before the day of the study. Measurements of glomerular hemodynamics were performed in both unstimulated with basal renal nerve traffic eliminated and during exogenous renal nerve stimulation (RNS) (3 Hz). RNS decreased glomerular capillary hydrostatic pressure and single-nephron plasma flow to a similar extent in all three dietary conditions via increases in afferent arteriolar resistance. The data demonstrated that dietary preconditioning does not alter the glomerular hemodynamic response to an exogenous, fixed RNS. Glomerular prostaglandin E2 production and plasma renin activity were significantly greater in rats fed a low-salt diet compared with either normal- or high-salt diet. The constancy of glomerular hemodynamic responses to RNS in spite of wide variations in dietary salt intake indicates that functional renal hemodynamic differences observed as a result of NaCl intake must be primarily the consequence of differences in renal nerve traffic and not hormonal alterations.

Absorption↗
PubMed1990

Glomerular hemodynamics and alpha 2-adrenoreceptor stimulation: the role of renal nerves.

We evaluated the effects of alpha 2-adrenoceptor stimulation on the determinants of nephron filtration rate (SNGFR) using micropuncture in Munich-Wistar rats. Micropuncture was performed in animals 5-7 days after sham surgery (group 1) or renal denervation (DNX) (groups 2, 3, and 4). Glomerular hemodynamic measurements were made before and during a systemic infusion of the alpha 2-agonist, B-HT 933 (1.0 mg.kg-1.h-1) (groups 1, 2, and 3). Group 3 rats were pretreated with the alpha 2-antagonist, yohimbine (3 mg.kg-1.h-1). In group 4, hydralazine was substituted for B-HT 933 to dissociate specific alpha 2-effects from nonspecific effects on blood pressure. Arterial pressure declined by similar amounts between experimental periods in groups 1, 2, and 4. In group 1, B-HT 933 caused SNGFR to increase due to an increment in nephron plasma flow. In group 2, B-HT 933 caused SNGFR to decrease due to a decrement in glomerular ultrafiltration coefficient (LpA). In groups 3 and 4, SNGFR was unaffected by B-HT 933 or hydralazine. Ligand-binding studies in glomerular membranes documented the presence of alpha 2-adrenoreceptors (275 +/- 22 fmol/mg protein). Receptor density was not altered by DNX. These observations could be explained by an alpha 2-mediated inhibition of renal nerve activity combined with intrinsic sympathomimetic effects not dependent on renal nerves, with the latter effects unmasked by DNX and manifested by a decrease in LpA.

Adrenergic alpha-Agonists↗
PubMed1990

Acute and subacute prostaglandin and ANG II inhibition on glomerulotubular dynamics in rats.

Prostaglandins (PG) and angiotensin II (ANG II) contribute to regulation of glomerular microcirculation. Acute vs. chronic physiological alterations of glomerular hemodynamics that result from inhibition of either PG or ANG II, or both, and their interaction were examined. Four groups of Munich-Wistar rats were submitted to the following micropuncture studies in euvolemic conditions for measurements of glomerular hemodynamics and tubular fluid reabsorption: 1) an untreated control group, 2) 4- to 6-day inhibition of both PG and angiotensin-converting enzyme activity with meclofenamate and MK-421 (enalapril), 3) 4- to 6-day treatment with enalapril followed by acute PG inhibition in the second measurement period, 4) 4- to 6-day PG inhibition followed by acute enalapril treatment in the second period. Dual 4- to 6-day treatment decreased single-nephron filtration rate (SNGFR, 24 +/- 2 vs. 33 +/- 2 nl/min in control; P less than 0.05) as a result of decreases in single-nephron plasma flow (SNPF) and glomerular hydrostatic pressure gradient (delta P). Treatment with enalapril alone for 4-6 days did not reduce SNGFR and SNPF; however, delta P decreased. Acute addition of meclofenamate did not alter these factors. SNGFR was decreased with 4- to 6-day treatment of meclofenamate from 33 +/- 2 in control to 25 +/- 1 nl/min (P less than 0.05). Acute treatment with enalapril in the 4- to 6-day meclofenamate-treated rats increased SNGFR to values not different from control. The results demonstrated that glomerular hemodynamic alterations consequent to inhibition of ANG II and PG systems differ between chronic and acute treatments. Therefore, interpretation of the role of individual hormonal systems in the control of glomerular hemodynamics should be approached with caution, since effects may be altered by duration of treatment and involvement of other vasoactive systems.

Absorption↗
PubMed1990

Cyclooxygenase-dependent mediators of renal hemodynamic function in female rats.

Previous studies have revealed a sex-dependent difference in response to cyclooxygenase inhibition in anesthetized male and female rats. Female rats have shown an unexpected vasodilation in response to prostaglandin (PG) inhibition. The present studies were designed to further investigate the sex-dependent role of the PG system in the control of normal renal hemodynamics in female Munich-Wistar rats. Renal hemodynamic studies were performed on anesthetized female rats before and during acute cyclooxygenase inhibition using a variety of protocols. One group underwent subacute unilateral renal denervation. A separate group was chronically catheterized and plasma catecholamines were measured during the awake state and then after anesthesia under the euvolemic protocol. Another group was administered the angiotensin II blocker, saralasin, before and during cyclooxygenase inhibition. In a final group, flow to the distal nephron was interrupted via placement of a wax block into the late proximal tubule to determine the role of distal nephron flow and tubuloglomerular feedback in the glomerular response to cyclooxygenase inhibition. It was determined that neither the wax block nor saralasin administration attenuated the vasodilatory response observed in normal female rats due to cyclooxygenase inhibition; however, subacute unilateral renal denervation completely blocked the vasodilatory response to PG inhibition in these female Munich-Wistar rats. Plasma catecholamines were found to be similar whether awake or under anesthesia. These studies indicate the importance of the adrenergic system in modulating PG production in the acutely anesthetized intact female rat.

Anesthesia↗