Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats

1992 ◽  
Vol 263 (5) ◽  
pp. R1064-R1070 ◽  
Author(s):  
S. Lu ◽  
R. J. Roman ◽  
D. L. Mattson ◽  
A. W. Cowley
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urine Flow ◽  
Water Excretion ◽  
Doppler Flowmetry ◽  
Blood Flows ◽  
Electromagnetic Flow Probe ◽  
Interstitial Infusion

The role of renal papillary blood flow in regulation of fluid and electrolyte excretion was examined. The effects of an acute infusion of diltiazem (5 micrograms.kg-1 x min-1) into the renal medullary interstitium on papillary blood flow and sodium and water excretion were studied. Changes of renal blood flow were measured using an electromagnetic flow probe. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Renal and cortical blood flows were unchanged during medullary interstitial infusion of diltiazem, but papillary blood flow increased 26% (P < 0.05) and remained elevated for 1 h after diltiazem infusion was discontinued. Glomerular filtration rate (GFR) of the infused kidney increased by 21% from a control of 1.0 +/- 0.1 ml.min-1 x g-1 during infusion of diltiazem (P < 0.05), but it returned to control after diltiazem infusion was stopped. Urine flow and sodium excretion increased by 70% (P < 0.05), and fractional sodium excretion rose from 1.5 +/- 0.2 to 2.4 +/- 0.3% of the filtered load during the hour after diltiazem infusion. Renal blood flow, cortical and papillary blood flow, GFR, urine flow, and sodium excretion in the 0.9% sodium chloride vehicle-infused kidney were not significantly altered during the experiment. Intravenous infusion of the same dose of diltiazem (5 micrograms.kg-1 x min-1) increased GFR by 22%, but had no effect on urine flow and sodium excretion. These results indicate that renal medullary interstitial infusion of diltiazem selectively increased renal papillary blood flow, which was associated with an increase of sodium and water excretion.

Role of renal medullary adenosine in the control of blood flow and sodium excretion

1999 ◽  
Vol 276 (3) ◽  
pp. R790-R798 ◽  
Author(s):  
Ai-Ping Zou ◽  
Kasem Nithipatikom ◽  
Pin-Lan Li ◽  
Allen W. Cowley
Keyword(s):  
Blood Flow ◽  
Sodium Excretion ◽  
Renal Medulla ◽  
Urine Flow ◽  
Doppler Flowmetry ◽  
Blood Flows ◽  
Medullary Blood Flow ◽  
Adenosine Concentration ◽  
Interstitial Infusion

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.

Influence of kinins and angiotensin II on the regulation of papillary blood flow

1988 ◽  
Vol 255 (4) ◽  
pp. F690-F698 ◽  
Author(s):  
R. J. Roman ◽  
M. L. Kaldunski ◽  
A. G. Scicli ◽  
O. A. Carretero
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Sodium Bicarbonate ◽  
Sodium Excretion ◽  
Sodium Bicarbonate Solution ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Water Excretion ◽  
Cortical Blood Flow ◽  
Blood Flows

The influence of kinins and angiotensin II on the regulation of renal cortical and papillary blood flow and sodium and water excretion was examined in rats. Superficial cortical and papillary blood flows were measured using a laser-Doppler flowmeter. Papillary blood flow increased 50% after enalaprilat (60 micrograms/kg) and phosphoramidon (5.5 micrograms.kg-1.min-1) were given along with 0.3 M sodium bicarbonate solution to inhibit degradation of kinins and enhance urinary kallikrein activity. Infusion of a kinin antagonist, D-Arg-Hyp-Thi-D-Phe-bradykinin (5 micrograms/min), returned papillary blood flow to control levels. Urine flow and sodium excretion increased after the administration of the kininase inhibitors and sodium bicarbonate, while glomerular filtration rate (GFR) and outer cortical blood flow were unaltered. The kinin antagonist did not alter sodium and water excretion in rats receiving the kininase inhibitors and bicarbonate. Administration of the kinin antagonist alone lowered papillary blood flow by 20%, without affecting outer cortical blood flow or GFR. Urine flow decreased and urine osmolality increased after the rats received the kinin antagonist, but sodium excretion remained unaltered. To assess the role of angiotensin II in the control of papillary blood flow, kinin receptors were blocked by infusion of an antagonist, and the effects of enalaprilat and saralasin were studied. Papillary blood flow increased after blockade of the angiotensin II system in rats receiving the kinin antagonist. These results indicate that the kallikrein-kinin and renin-angiotensin systems participate in the regulation of papillary blood flow.

Effects of acute AT1 receptor blockade by candesartan on arterial pressure and renal function in rats

1998 ◽  
Vol 274 (5) ◽  
pp. F940-F945 ◽  
Author(s):  
Ludek Cervenka ◽  
Chi-Tarng Wang ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urine Flow ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Doppler Flowmetry ◽  
Higher Doses ◽  
Very High

Experiments were performed on normal anesthetized rats to determine the effects of candesartan, a novel AT1 receptor antagonist, on the arterial pressure and renal hemodynamic responses to bolus doses of angiotensin II (ANG II) and on renal hemodynamics and sodium excretion. Control arterial pressure responses to bolus ANG II doses of 10, 50, 100 and 1,000 ng were 26 ± 6, 54 ± 7, 57 ± 7, and 79 ± 7 mmHg; the decreases in cortical renal blood flow (CRBF), measured with laser-Doppler flowmetry, were 47 ± 9, 64 ± 8, 71 ± 6, and 82 ± 6%. The vasoconstrictor responses to ANG II up to 1,000 ng were completely blocked by candesartan doses of 1 and 0.1 mg/kg, whereas treatment with 0.01 mg/kg candesartan attenuated the arterial pressure and CRBF responses. The higher doses of candesartan (1 and 0.1 mg/kg) elicited rapid decreases in arterial pressure, leading to associated decreases in sodium excretion. Renal blood flow (RBF), glomerular filtration rate (GFR), and urine flow also decreased following treatment with candesartan at 1 mg/kg. In contrast, when candesartan was given at 0.01 mg/kg, which did not decrease arterial pressure significantly, there were significant increases in GFR (16 ± 4), RBF (9 ± 2), urine flow (11 ± 2), sodium excretion (35 ± 7), and fractional sodium excretion (39 ± 8%). The inability to overcome blockade, even with very high ANG II doses, indicates that candesartan is a potent noncompetitive blocker of ANG II pressor and renal vasoconstrictor effects. The lower candesartan dose that did not cause significant hypotension elicited substantial increases in RBF, GFR, and sodium excretion, revealing the direct renal vasodilator and natriuretic effects of AT1 receptor blockade.

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

2000 ◽  
Vol 279 (4) ◽  
pp. R1268-R1276 ◽  
Author(s):  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou ◽  
Ole Skøtt
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Sodium Reabsorption ◽  
Osmotic Diuresis ◽  
Nacl Concentration ◽  
Proximal Tubular ◽  
Distal Tubules

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (EDNaCl) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, EDNaCl fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), EDNaClincreased by 3.6 mM, ( P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 μmol NaCl in a smaller volume caused EDNaCl to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron EDNaCl and PRC. We conclude that EDNa decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.

Endothelin resets renal blood flow autoregulatory efficiency during acute blockade of NO in the rat

2001 ◽  
Vol 281 (6) ◽  
pp. F1132-F1140 ◽  
Author(s):  
R. Kramp ◽  
P. Fourmanoir ◽  
N. Caron
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Receptor Subtypes ◽  
Receptor Blockade ◽  
Flow Probe ◽  
Relative Contribution ◽  
No Inhibition ◽  
Electromagnetic Flow Probe ◽  
Bq 610

First published August 15, 2001; 10.1152/ajprenal.00078.2001.—Renal blood flow (RBF) autoregulatory efficiency may be enhanced during NO inhibition in the rat, as recently reported. Under these conditions, endothelin (ET) synthesis and release may be increased. Our purpose was therefore to determine the role of ET in RBF autoregulatory changes induced by NO inhibition. To address this point, ETA/B receptors were blocked in anesthetized rats with bosentan, or selectively with BQ-610 or BQ-788. NO synthesis was inhibited with N G-nitro-l-arginine methyl ester (l-NAME). Mean arterial pressure (MAP) was decreased after bosentan (−10 mmHg; P < 0.01) or increased after l-NAME (25 mmHg; P < 0.001). RBF measured with an electromagnetic flow probe was reduced byl-NAME (−50%) and by BQ-788 (−24%). The pressure limits of the autoregulatory plateau (PA ∼100 mmHg) and of no RBF autoregulation (Po ∼80 mmHg) were significantly lowered by 15 mmHg after l-NAME but were unchanged after bosentan, BQ-610, or BQ-788. During NO inhibition, autoregulatory resetting was completely hindered by bosentan (PA ∼100 mmHg) and by ETB receptor blockade with BQ-788 (PA ∼106 mmHg), but not by ETA receptor blockade with BQ-610 (PA ∼85 mmHg). These results suggest that the involvement of ET in the RBF autoregulatory resetting occurs during NO inhibition, possibly by preferential activation of the ETB receptor. However, the relative contribution of ET receptor subtypes remains to be further specified.

scholarly journals Effects of serelaxin on renal microcirculation in rats under control and high-angiotensin environments

2018 ◽  
Vol 314 (1) ◽  
pp. F70-F80 ◽  
Author(s):  
Weijian Shao ◽  
Carla B. Rosales ◽  
Camila Gonzalez ◽  
Minolfa C. Prieto ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Excretion Rate ◽  
No Synthase ◽  
Urine Flow ◽  
Ang Ii ◽  
Afferent Arterioles

Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation, remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II-infused male rats. Serelaxin increased mean arterial pressure slightly and significantly increased renal blood flow, urine flow, and sodium excretion rate. Group analysis of all serelaxin infusion experiments showed significant increases in GFR. During infusion with subthreshold levels of Ang II, serelaxin did not alter mean arterial pressure, renal blood flow, GFR, urine flow, or sodium excretion rate. Heart rates were elevated during serelaxin infusion alone (37 ± 5%) and in Ang II-infused rats (14 ± 2%). In studies using the in vitro isolated juxtamedullary nephron preparation, superfusion with serelaxin alone (40 ng/ml) significantly dilated afferent arterioles (10.8 ± 1.2 vs. 13.5 ± 1.1 µm) and efferent arterioles (9.9 ± 0.9 vs. 11.9 ± 1.0 µm). During Ang II superfusion, serelaxin did not alter afferent or efferent arteriolar diameters. During NO synthase inhibition (l-NNA), afferent arterioles also did not show any vasodilation during serelaxin infusion. In conclusion, serelaxin increased overall renal blood flow, urine flow, GFR, and sodium excretion and dilated the afferent and efferent arterioles in control conditions, but these effects were attenuated or prevented in the presence of exogenous Ang II and NO synthase inhibitors.

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

1987 ◽  
Vol 65 (11) ◽  
pp. 2219-2224 ◽  
Author(s):  
J. Krayacich ◽  
R. L. Kline ◽  
P. F. Mercer
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Fractional Excretion Of Sodium ◽  
Infusion Of Norepinephrine

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.

Mechanism of natriuresis during intrarenal infusion of prostaglandins

1984 ◽  
Vol 247 (3) ◽  
pp. F475-F479 ◽  
Author(s):  
J. A. Haas ◽  
T. G. Hammond ◽  
J. P. Granger ◽  
E. H. Blaine ◽  
F. G. Knox
Keyword(s):  
Blood Flow ◽  
Hydrostatic Pressure ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Prostaglandin Analogue ◽  
Similar Increase ◽  
Interstitial Pressure

Intrarenal infusion of the natural prostaglandin PGE2 increases renal blood flow, renal interstitial hydrostatic pressure, and urinary sodium excretion. A newly synthesized prostaglandin analogue, 4-3-[3-[2-(1-hydroxycyclohexyl)- ethyl]-4-oxo-2-thiazolidinyl]propyl benzoic acid, increases renal blood flow without increasing sodium excretion. To investigate the role of renal interstitial hydrostatic pressure in this dissociation, comparisons were made between PGE2 and the prostaglandin analogue. Intrarenal infusion of PGE2 increased renal blood flow, renal interstitial hydrostatic pressure, and urinary sodium excretion. Following a similar increase in renal blood flow with intrarenal infusion of prostaglandin analogue, renal interstitial hydrostatic pressure and urinary sodium excretion were not changed. To determine whether increases in urinary sodium excretion due to PGE2 infusion are causally related to the increase in renal interstitial hydrostatic pressure rather than to the increase in renal blood flow, responses to PGE2 were obtained in the absence of increases in interstitial pressure. When renal interstitial hydrostatic pressure was held constant, urinary sodium excretion did not change although there was a marked increase in renal blood flow. We conclude that increased renal interstitial hydrostatic pressure is necessary to produce an increase in urinary sodium excretion with prostaglandin-mediated renal vasodilation.

Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow

1994 ◽  
Vol 266 (2) ◽  
pp. F275-F282 ◽  
Author(s):  
A. P. Zou ◽  
J. D. Imig ◽  
M. Kaldunski ◽  
P. R. Ortiz de Montellano ◽  
Z. Sui ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Epoxyeicosatrienoic Acids ◽  
Blood Flows ◽  
Renal Perfusion Pressure ◽  
Renal Vascular

The present study evaluated the role of endogenous P-450 metabolites of arachidonic acid (AA) on autoregulation of renal blood flow in rats. Whole kidney and cortical blood flows were well autoregulated when renal perfusion pressure was varied from 150 to 100 mmHg. Infusion of 17-octadecynoic acid (17-ODYA) into the renal artery (33 nmol/min) increased cortical and papillary blood flows by 12.6 +/- 2.5 and 26.5 +/- 4.6%, respectively. After 17-ODYA, autoregulation of whole kidney and cortical blood flows was impaired. Intrarenal infusion of miconazole (8 nmol/min) had no effect on autoregulation of whole kidney, cortical, or papillary blood flows. 17-ODYA (1 microM) inhibited the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) and 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) by renal preglomerular microvessels in vitro by 83.7 +/- 7.4% and 89.0 +/- 4.9%, respectively. Miconazole (1 microM) reduced the formation of EETs by 86.4 +/- 5.7%, but it had no effect on the production of 20-HETE. These results suggest that endogenous P-450 metabolites of AA, particularly 20-HETE, may participate in the autoregulation of renal blood flow.

Contribution of renal prostaglandins to the natriuretic action of bradykinin in the dog

1979 ◽  
Vol 237 (3) ◽  
pp. F182-F187
Author(s):  
M. C. Blasingham ◽  
A. Nasjletti
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urine Volume ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Prostaglandin Synthetase ◽  
Renal Functions ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Stimulation Of

To study the effects of stimulation of renal prostaglandin biosynthesis by bradykinin, we assessed the changes in renal functions induced by intrarenal infusion of bradykinin (10 ng . min-1 . kg-1) in the dog anesthetized with pentobarbital before and during inhibition of prostaglandin synthesis by sodium meclofenamate (5 mg/kg). Before meclofenamate administration, bradykinin augmented the urinary output of a "PGE"-like substance from 1.00 +/- 0.25 to 3.88 +/- 1.09 ng/min (P less than 0.05) and increased renal blood flow by 65 +/- 9 ml/min (P less than 0.001), urine flow by 0.55 +/- 0.23 ml/min (P less than 0.05), and sodium excretion by 64.8 +/- 18.0 mueq/min (P less than 0.01). Administration of meclofenamate did not affect the bradykinin-induced increase in renal blood flow and urine volume, but suppressed the evoked output of "PGE" and reduced the associated natriuresis, i.e., sodium excretion increased by only 11.1 +/- 4.8 mueq/min (P greater than 0.05). In contrast, meclofenamate did not affect the natriuresis effected by an equidilator dose of PGE2 (5 ng . min-1 . kg-1) infused intrarenally. These observations suggest that a product of prostaglandin synthetase produced by the kidney during intrarenal infusion of bradykinin contributes to the natriuretic action of the peptide.

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