Acute Renal Medullary Interstitial Infusion of either saline or 2% albumin indistinctly rises RIHP and RMBF in the rat

This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 ± 5.2 nM, which was significantly higher than 55.6 ± 5.3 nM in the renal cortex ( n = 9). Renal medullary interstitial infusion of a selective A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol ⋅ kg−1 ⋅ min−1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol ⋅ kg−1 ⋅ min−1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol ⋅ kg−1 ⋅ min−1( n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3receptor agonist, N 6-benzyl-5′-( N-ethylcarbonxamido)adenosine (300 pmol ⋅ kg−1 ⋅ min−1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.

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Effect of renal interstitial infusion of arachidonic acid on proximal sodium reabsorption

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f237 ◽

1989 ◽

Vol 257 (2) ◽

pp. F237-F242 ◽

Cited By ~ 1

Author(s):

Y. Kinoshita ◽

J. C. Romero ◽

F. G. Knox

Keyword(s):

Arachidonic Acid ◽

Urinary Excretion ◽

Proximal Tubules ◽

Sodium Reabsorption ◽

Renal Interstitium ◽

Tubular Sodium Reabsorption ◽

Proximal Tubular ◽

The Individual ◽

Stimulation Of ◽

Interstitial Infusion

The effect of prostaglandins (PGs) on proximal sodium reabsorption has not been fully defined. The objective of the present study was to determine the response of proximal tubular sodium reabsorption to infusions of arachidonic acid and specific PGs into the renal interstitium in rats. Renal interstitial infusions of arachidonic acid as well as the individual PGs, I2, E2, and F2 alpha, were employed to elevate the concentration of these PGs in the kidney. Infusion of 10(-4) M arachidonic acid elicited a marked increase of urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2) from 260.1 +/- 52.7 to 507.4 +/- 129.5 pg/min (P less than 0.05) and a smaller increase of PGE2 from 18.4 +/- 11.2 to 25.9 +/- 10.9 pg/min (P less than 0.05). When micropuncture samples were obtained from superficial late proximal tubules, infusion of arachidonic acid increased the fractional delivery of sodium (FDNa) from 47.8 +/- 5.9 to 58.3 +/- 4.6% (n = 6, P less than 0.01). In the presence of indomethacin, arachidonic acid failed to augment FDNa. Infusion of 10(-5) M PGI2 also increased FDNa from 51.4 +/- 3.4 to 64.0 +/- 4.4% (n = 10, P less than 0.01). PGF2 alpha did not change FDNa and PGE2 decreased it from 53.1 +/- 5.4 to 37.4 +/- 3.3% (n = 8, P less than 0.01). In summary, the present study demonstrates that renal interstitial infusion of arachidonic acid decreases sodium reabsorption by the superficial proximal tubules possibly through the stimulation of PGI2 production.

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Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.267.5.r1217 ◽

1994 ◽

Vol 267 (5) ◽

pp. R1217-R1225 ◽

Cited By ~ 4

Author(s):

E. Szczepanska-Sadowska ◽

K. Stepniakowski ◽

M. M. Skelton ◽

A. W. Cowley

Keyword(s):

Arterial Pressure ◽

Intravenous Administration ◽

Plasma Osmolality ◽

Sprague Dawley ◽

Sustained Hypertension ◽

Body Sodium ◽

Chronic Infusion ◽

Vasopressin Receptors ◽

Stimulation Of ◽

Interstitial Infusion

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.

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Mechanism of prostaglandin E2-induced increase of proximal sodium reabsorption in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.1.r82 ◽

1990 ◽

Vol 258 (1) ◽

pp. R82-R86 ◽

Cited By ~ 1

Author(s):

Y. Kinoshita ◽

F. G. Knox

Keyword(s):

Angiotensin Ii ◽

Prostaglandin E2 ◽

Rat Kidney ◽

Sodium Reabsorption ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Convoluted Tubules ◽

Stimulation Of ◽

Interstitial Infusion

Prostaglandin E2, when infused directly into the renal interstitium, enhances sodium reabsorption by the superficial proximal convoluted tubules of anesthetized Sprague-Dawley rats. The present study was designed to investigate the role of angiotensin II in the prostaglandin E2-induced stimulation of proximal sodium reabsorption. Micropuncture at the superficial late proximal tubule demonstrated a significant increase in the fractional reabsorption of sodium from 39.9 +/- 2.3% in control conditions to 51.8 +/- 3.0% (n = 9, P less than 0.01) during the renal interstitial infusion of prostaglandin E2. The stimulatory effect of prostaglandin E2 on proximal sodium reabsorption was markedly attenuated by pretreatment with saralasin. During intravenous saralasin infusion, prostaglandin E2 did not significantly change the fractional reabsorption of sodium from 42.2 +/- 5.8 to 45.4 +/- 6.0% (n = 7, NS). In summary, the stimulatory effect of renal interstitial infusion of prostaglandin E2 on proximal sodium reabsorption was attenuated by pretreatment with saralasin. Therefore renal interstitial infusion of prostaglandin E2 may enhance proximal sodium reabsorption, at least in part, through stimulation of angiotensin II production in the rat kidney.

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INTRAPARENCHYMAL AND INTRATUMORAL INTERSTITIAL INFUSION OF ANTI-GLIOMA MONOCLONAL ANTIBODY 8H9

Neurosurgery ◽

10.1227/01.neu.0000334052.60634.84 ◽

2008 ◽

Vol 63 (6) ◽

pp. 1166-1174 ◽

Cited By ~ 13

Author(s):

Neal Luther ◽

Nai-Kong V. Cheung ◽

Ira J. Dunkel ◽

Justin F. Fraser ◽

Mark A. Edgar ◽

...

Keyword(s):

Monoclonal Antibody ◽

Interstitial Infusion

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Interstitial Infusion of IL13-PE38QQR in the Rat Brain Stem

Journal of Neuro-Oncology ◽

10.1023/b:neon.0000024219.47447.91 ◽

2004 ◽

Vol 67 (3) ◽

pp. 287-293 ◽

Cited By ~ 18

Author(s):

Mark M. Souweidane ◽

Giuseppe Occhiogrosso ◽

Erika B. Mark ◽

Mark A. Edgar

Keyword(s):

Brain Stem ◽

Rat Brain ◽

Interstitial Infusion

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Renal medullary interstitial infusion ofl-arginine prevents hypertension in Dahl salt-sensitive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.5.r1667 ◽

1998 ◽

Vol 275 (5) ◽

pp. R1667-R1673 ◽

Cited By ~ 19

Author(s):

Noriyuki Miyata ◽

Ai Ping Zou ◽

David L. Mattson ◽

Allen W. Cowley

Keyword(s):

Blood Flow ◽

Control Period ◽

Renal Medulla ◽

High Salt ◽

No Production ◽

Medullary Blood Flow ◽

Induced Hypertension ◽

Renal Medullary Blood Flow ◽

Wistar Kyoto ◽

Interstitial Infusion

Studies were designed to examine the effects of renal medullary interstitial infusion of l-arginine (l-Arg) on the development of high-salt-induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of l-Arg (300 μg ⋅ kg−1 ⋅ min−1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose ofl-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullaryl-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 ± 2 to 167 ± 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion ofl-Arg alone in DR rats (control = 104 ± 1 mmHg) or in WKY rats (control = 120 ± 3 mmHg) and was not significantly changed from these levels during the 7 days ofl-Arg infusion combined with high-NaCl diet. The same amount of l-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 μg ⋅ kg−1 ⋅ min−1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving l-Arg (300 μg ⋅ kg−1 ⋅ min−1iv) exhibited an increase in plasma l-Arg from control concentrations of 138 ± 11 to 218 ± 4 μmol/l, while MAP, which averaged 124 ± 3 mmHg during the 3-day control period, rose to 165 ± 5 mmHg by day 5of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of l-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.

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Effects of renal medullary infusion of a vasopressin V1 agonist on renal antihypertensive mechanisms in rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.1.r76 ◽

1998 ◽

Vol 275 (1) ◽

pp. R76-R85 ◽

Cited By ~ 2

Author(s):

Göran Bergström ◽

Roger G. Evans

Keyword(s):

Receptor Agonist ◽

Perfusion Pressure ◽

Renal Perfusion ◽

Receptor Activation ◽

Urine Flow ◽

Extracorporeal Circuit ◽

Renal Perfusion Pressure ◽

Chronic Activation ◽

Cortical Perfusion ◽

Interstitial Infusion

The factors responsible for the development of hypertension during chronic activation of intrarenal V1receptors are unknown. We therefore tested whether medullary interstitial infusion of the selective V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin (V1 agonist) influences renal antihypertensive mechanisms initiated by increased renal perfusion pressure (RPP). In intact anesthetized rabbits, the V1 agonist (10 ng ⋅ kg−1 ⋅ min−1) reduced medullary perfusion by 36 ± 7%, whereas cortical perfusion was reduced by only 14 ± 2%. An extracorporeal circuit was used to increase RPP in a stepwise manner from 65 to 85, 110, 130, and 160 mmHg for consecutive 20-min periods. Increased RPP reduced mean arterial pressure by 35 ± 8% in vehicle-treated rabbits, but by only 10 ± 3% in V1agonist-treated rabbits. Simultaneously, pressure-diuresis-natriuresis was induced; urine flow and sodium excretion increased similarly in the two groups of rabbits, but hematocrit did not change. We suggest that the depressor response to increased RPP is mainly due to release of a putative renal medullary depressor hormone (RMDH). Suppression of the release and/or actions of RMDH may therefore contribute to the hypertensive effect of chronic V1receptor activation.

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Effects of adenosine infusion into renal interstitium on renal hemodynamics

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.4.f678 ◽

1987 ◽

Vol 252 (4) ◽

pp. F678-F682 ◽

Cited By ~ 7

Author(s):

D. Pawlowska ◽

J. P. Granger ◽

F. G. Knox

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Steady State ◽

Filtration Rate ◽

Rat Kidney ◽

Hemodynamic Effects ◽

Adenosine Receptor Antagonist ◽

Renal Interstitium ◽

Adenosine Agonists ◽

Interstitial Infusion

This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. Infusion of adenosine (bolus 0.5 mumol plus 0.1 mumol/min) decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 (mean +/- SE) to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), (bolus 10 nmol plus 2 nmol/min) decreased GFR from 0.73 +/- 0.07 to 0.21 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, [3H]NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. We conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine.

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Comparison of systemic and direct intrarenal angiotensin II blockade on sodium excretion in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1995.269.1.f40 ◽

1995 ◽

Vol 269 (1) ◽

pp. F40-F46 ◽

Cited By ~ 2

Author(s):

Y. Peng ◽

F. G. Knox

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Mean Arterial Pressure ◽

Sodium Excretion ◽

Systemic Effects ◽

Ang Ii ◽

High Sodium ◽

Sodium Diet ◽

High Sodium Diet ◽

Interstitial Infusion

To dissociate the renal effects from the systemic effects of angiotensin II blockade, the present study was designed to determine the effects of systemic and renal interstitial infusion of the specific angiotensin II (ANG II) receptor antagonist, losartan, on blood pressure and sodium excretion in rats fed a low-, normal, or high-sodium diet. Fractional sodium excretion (FENa) and mean arterial pressure (MAP) were measured in rats before and during systemic infusion of losartan (10 mg/kg) or renal interstitial infusion of losartan (3 mg/kg) by means of a chronically implanted matrix. In rats fed a low- or normal sodium diet, systemic infusion of losartan markedly decreased MAP (delta -21 +/- 2, delta -10 +/- 2 mmHg, respectively; P < 0.05) with an accompanying fall in FENa (delta -0.10 +/- 0.05, delta -0.91 +/- 0.40%, respectively; P < 0.05). In contrast, preferential blockade of renal ANG II with renal interstitial losartan infusion resulted in an increase in FENa (delta 0.13 +/- 0.04, delta 0.95 +/- 0.45%, respectively; P < 0.05) and no significant change in MAP. In rats fed a high-sodium diet, both systemic and renal interstitial infusion of losartan increased FENa (delta 1.90 +/- 0.26, delta 1.40 +/- 0.56%, respectively; P < 0.05). Although systemic infusion of losartan decreased MAP (delta -4.4 +/- 0.6 mmHg, P < 0.05) in rats fed a high-sodium diet, the reduction in MAP was much less than that in rats fed a low- and normal sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

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