scholarly journals Bosentan Normalizes the GFR Response to Renal Nerve Stimulation Following Reversible Unilateral Ureteric Obstruction in the Rat

2014 ◽  
pp. 713-722
Author(s):  
F. T. HAMMAD ◽  
A. M. WHEATLEY ◽  
G. DAVIS
Keyword(s):  
Glomerular Filtration Rate ◽  
Flow Rate ◽  
Nerve Stimulation ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Urine Flow ◽  
Ureteric Obstruction ◽  
Renal Nerve ◽  
Renal Nerve Stimulation ◽  
Unilateral Ureteric Obstruction

We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ETA/B receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37±3 %, P<0.001), and absolute (38±4 %, P<0.001) and fractional (35±5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22±3 % (P<0.01), but reduced urine flow rate (14±2 %, P<0.001) and fractional sodium excretion (23±5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction.

Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension

1997 ◽  
Vol 272 (2) ◽  
pp. H679-H687
Author(s):  
M. Naitoh ◽  
H. Suzuki ◽  
K. Arakawa ◽  
A. Matsumoto ◽  
A. Ichihara ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Receptor Antagonist ◽  
Flow Rate ◽  
Ace Inhibitors ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Ang Ii ◽  
Low Renin Hypertension

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

The Role of Prostaglandins in Glucagon-Induced Natriuresis

1980 ◽  
Vol 58 (5) ◽  
pp. 393-401 ◽  
Author(s):  
M. A. Kirschenbaum ◽  
E. T. Zawada
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Prostaglandin E ◽  
Excretion Rates

1. Three groups of anaesthetized dogs were studied to determine the role of renal prostaglandins in glucagon-induced natriuresis. 2. Urine flow, sodium and prostaglandin E excretion rates increased significantly in the experimental kidney with glucagon infusion (0.20 μg/min) into the renal artery. These changes were completely reversed after the administration of either of two inhibitors of prostaglandin synthesis. 3. Infusion of glucagon (0.20 μg/min) after the administration of either of the prostaglandin synthetase inhibitors failed to increase either urine flow rate or sodium excretion above control values and failed to elevate urine prostaglandin E excretion rates. 4. Infusion of glucagon (0.75–1.25 μg/min) resulted in significant elevations in urine flow rate, glomerular filtration rate, renal plasma flow, urine sodium and prostaglandin E excretion rates. 5. The data presented indicate that the diuresis and natriuresis seen with the infusion of glucagon (0.20 μg/min) are accompanied by an increase in urine prostaglandin E excretion and are reversed by the administration of inhibitors of prostaglandin synthesis, suggesting that the increased urine flow and sodium excretion rates are dependent on prostaglandin-mediated mechanisms. The administration of glucagon in higher doses appears to be associated with alterations in electrolyte excretion and glomerular filtration rate, which presumably is related to factors other than prostaglandin synthesis and release.

Differential Efect of Noradrenaline and Renal Nerve Stimulation on Vascular Resistance in the Dog Kidney and the Release of a Prostaglandin E-Like Substance

1972 ◽  
Vol 42 (2) ◽  
pp. 223-233 ◽  
Author(s):  
J. C. McGiff ◽  
K. Crowshaw ◽  
N. A. Terragno ◽  
K. U. Malik ◽  
A. J. Lonigro
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Nerve Stimulation ◽  
Venous Blood ◽  
Urine Flow ◽  
Rapid Recovery ◽  
Prostaglandin E ◽  
Early Recovery ◽  
Renal Nerve ◽  
Renal Nerve Stimulation

1. The concentrations of prostaglandin E(PGE)- and prostaglandin F(PGF)-like substances in renal venous blood were determined by parallel bioassay of extracts of renal venous effluent before and during adrenergic stimulation of the kidney and were related to simultaneous measurements of renal blood flow and urine flow. 2. When noradrenaline was infused continuously into the renal artery, its initial vasoconstrictor and antidiuretic effects diminished on seven of eight occasions in six dogs. Rapid recovery of renal blood flow and urine flow was invariably associated with increasing concentration in renal venous blood of a substance having the physicochemical, chromatographic and biological properties of a prostaglandin of the E series. In the one instance when rapid early recovery of renal blood flow was not observed the concentration of PGE-like substance was not increased. 3. In contrast, during renal nerve stimulation early rapid recovery of renal blood flow and urine flow did not occur and the concentration of a PGE-like substance in renal venous blood did not increase. The concentration of a PGF-like substance in renal venous effluent did not increase in response to either stimulus. 4. Since PGE2, unlike PGF2α, is a potent renal vasodilator and diuretic, the intrarenal release of this substance by noradrenaline in concentrations similar to those determined for a PGE-like substance (>0·50 ng/ml assayed as PGE2 equivalents) would account for the changes in renal blood flow and urine flow in these experiments when the renal actions of noradrenaline were attenuated. 5. These results support the proposal that renal prostaglandins function in an intrarenal negative feedback control system which regulates antidiuretic and vasoconstrictor systems.

Renal nerve stimulation augments effect of intraluminal angiotensin II on proximal tubule transport

2002 ◽  
Vol 282 (6) ◽  
pp. F1043-F1048 ◽  
Author(s):  
Albert Quan ◽  
Michel Baum
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Nerve Stimulation ◽  
Filtration Rate ◽  
Renin Angiotensin System ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Angiotensin System ◽  
Renal Nerve Stimulation

The proximal tubule synthesizes and secretes angiotensin II into the lumen, where it regulates transport. Renal denervation abolishes the effect of angiotensin II on proximal tubule transport. Using in vivo microperfusion, we examined whether renal nerve stimulation modulates the effect of angiotensin II on transport. The effect of angiotensin II was assessed by measuring the decrease in volume reabsorption with the addition of 10−4M luminal enalaprilat. Luminal enalaprilat did not alter volume reabsorption (2.80 ± 0.18 vs. 2.34 ± 0.14 nl · mm−1 · min−1). However, with renal nerve stimulation, enalaprilat decreased volume reabsorption (3.45 ± 0.22 vs. 1.67 ± 0.20 nl · mm−1 · min−1, P < 0.0005). The absolute and percent decrements in volume reabsorption with luminal enalaprilat were higher with renal nerve stimulation than with native innervation (1.78 ± 0.19 vs. 0.46 ± 0.23 nl · mm−1 · min−1, P < 0.02, and 51.8 ± 5.0 vs. 14.6 ± 7.4%, P < 0.05, respectively). Renal nerve stimulation did not alter the glomerular filtration rate or renal blood flow. Renal nerve stimulation augments the stimulatory effect of intraluminal angiotensin II. The sympathetic renal nerves modulate the proximal tubule renin-angiotensin system and thereby regulate proximal tubule transport.

Action of Angiotensin I Converting Enzyme Inhibitor on the Control of Renal Function in the Cat

1979 ◽  
Vol 56 (4) ◽  
pp. 365-371 ◽  
Author(s):  
E. J. Johns
Keyword(s):  
Blood Flow ◽  
Enzyme Activity ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Nerve Stimulation ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Perfusion Pressure ◽  
Converting Enzyme ◽  
Sodium Clearance

1. The renal responses to low level renal nerve stimulation and reduction in renal perfusion pressure within the autoregulatory range were measured before and after blockade of converting enzyme activity. Experiments were carried out using the unilaterally nephrectomized cat with the nerves of the remaining kidney acutely sectioned. 2. Renal nerves were stimulated to cause a 14% fall in blood flow for 15 min. Glomerular filtration rate was unchanged but sodium excretion and the ratio of sodium clearance to glomerular filtration rate fell significantly. 3. Renal nerve stimulation after blockade of converting enzyme activity was associated with a significant fall in glomerular filtration rate. The reductions in sodium excretion and in the ratio of sodium clearance to glomerular filtration rate were as large as in the absence of the blocking drug. 4. Reduction in renal perfusion pressure was associated with autoregulation of both renal blood flow and glomerular filtration rate but with large falls in sodium excretion and the ratio of sodium clearance to glomerular filtration rate. 5. After blockade of converting enzyme activity blood flow was still autoregulated in response to similar perfusion pressure reduction and glomerular filtration rate fell significantly. The ratio of sodium clearance to glomerular filtration rate, and sodium excretion, were reduced to the same extent as in the absence of the drug. 6. This information suggests that regulation of glomerular filtration rate associated with nerve stimulation or pressure reduction may be mediated by the intrarenal formation of angiotensin II, possibly acting at the efferent arteriole. They also indicate that angiotensin II is probably not involved in causing the increased sodium reabsorption.

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.

Effect of vasopressin on sodium excretion and plasma antinatriferic activity in the dog

1976 ◽  
Vol 231 (1) ◽  
pp. 28-33 ◽  
Author(s):  
VM Buckalew ◽  
KA Dimond
Keyword(s):  
Glomerular Filtration Rate ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Urine Flow ◽  
Potassium Excretion ◽  
State Control ◽  
Sham Control ◽  
Anesthetized Dogs ◽  
Renal Tubular ◽  
Steady State Control

Vasopressin (VP) was administered for 1 h intravenously to hydropenic, anesthetized dogs in doses of 1.0-1.25 mU/kg per min. In 14 experiments, sodium excretion (UNA V) increased from a mean of 13 +/- 5 to a peak of 96 +/- 21 mueq/min 40 min after beginning infusion (P less than .001). Urine flow and potassium excretion increased from 0.18 +/-.04 ml/min and 20 +/- 2 meuq/min to peak values of 0.6 +/- .08 ml/min and 61 +/- 9 mueq/min, respectively (P less than .001), with no significant increase in glomerular filtration rate. No significant changes in UNA V occurred in eight sham control experiments of in six experiments in which VP was given at 75 muU/kf per min. To test the hypothesis that VP might be natriuretic indirectly by releasing a natriuretic substance, plasms ultrafiltrates were tested for toad bladder antinatriferic activity(AA). During steady-state control, AA was -10 +/- 3%. Thirty and sixty minutes after beginning VP, AA increased to -24 +/- 3% (P less than .05) and -26 +/- 2% (P less than .001), respectiviely. No significant change in plasma AA occurred in either sham controls or in animals given the subnatriuretic VP dose. Incubation of plasma with 1,000 muU/ml VP caused no increase in AA. The data show that VP natriuresis is accompanied by an increase in plasms AA. The results suggest that vasopressin natriuresis in hydropenic dogs at least in part to the release of a humoral inhibitor of renal tubular sodium transport.

Angiotensin-(1–7) in the ovine fetus

2001 ◽  
Vol 280 (2) ◽  
pp. R404-R409 ◽  
Author(s):  
Karen M. Moritz ◽  
Duncan J. Campbell ◽  
E. Marelyn Wintour
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Flow Rate ◽  
Filtration Rate ◽  
Plasma Concentrations ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Ang Ii ◽  
Arterial Blood

In the adult animal, ANG-(1–7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1–7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers ( n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1–7), and ANG II were 86 ± 21, 13 ± 2, and 14 ± 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 ± 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1–7) (2.9 ± 0.6 fmol/ml), whereas ANG II concentrations were not different (10 ± 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 ± 1.1 pmol ANG I · ml−1 · h−1) than in the ewe (0.9 ± 0.2 pmol · ml−1 · h−1, P < 0.05). Infusion of ANG-(1–7) (∼9 μg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1–7) reaching a maximum of 448 ± 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days ( n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1–7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT1 receptor, and AT2 receptor were elevated in kidneys of fetuses that received infusions of ANG-(1–7). Infusion of an ANG-(1–7) antagonist {[d-Ala7]-ANG-(1–7), 20 μg/h} for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1–7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1–7) may play a role in the fetal kidney.

CNS-induced natriuresis and renal hemodynamics in conscious rats

1983 ◽  
Vol 245 (6) ◽  
pp. F763-F771 ◽  
Author(s):  
D. Beasley ◽  
R. L. Malvin ◽  
D. R. Mouw
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Antidiuretic Hormone ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Plasma Renin ◽  
Renal Nerve ◽  
Natriuretic Hormone ◽  
Renal Nerve Activity

Sodium excretion was studied following experimental elevation of cerebrospinal fluid (CSF) sodium in heterozygous and homozygous (DI) Brattleboro rats given exogeneous antidiuretic hormone. Sodium excretion increased 4.5-fold in heterozygous and 3.5-fold in DI rats. The natriuresis in both groups was rapid in onset and occurred with a simultaneous kaliuresis. Blood pressure increased approximately 10 mmHg in the heterozygous but not in the DI rats. Accordingly, increased blood pressure may contribute to the natriuresis but is not the sole mechanism. Plasma renin concentration did not change in the DI rats during high Na CSF infusion, and chronic bilateral renal denervation did not abolish the natriuresis. Glomerular filtration rate increased during the high Na period in both the intact and renally denervated rats. These data provide evidence that a natriuretic mechanism exists that is not mediated by changes in antidiuretic hormone, renal nerve activity, mean arterial pressure, aldosterone, or angiotensin II, and thus may be due to another circulating substance or natriuretic hormone. This hormone may act totally or in part by increasing glomerular filtration rate.

Renal adrenergic effector mechanisms: glomerular sites for prostaglandin interaction

1988 ◽  
Vol 254 (2) ◽  
pp. F184-F190 ◽  
Author(s):  
J. C. Pelayo
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Wistar Rats ◽  
Filtration Rate ◽  
Renal Nerve ◽  
Single Nephron ◽  
Marked Decline ◽  
Renal Nerve Stimulation ◽  
Glomerular Ultrafiltration ◽  
Hydrostatic Pressure Difference

Micropuncture experiments were performed in Munich-Wistar rats to ascertain the renal microcirculatory sites at which prostaglandins interact with the renal nerve and angiotensin II. Renal nerve stimulation (RNS) of 3 Hz alone decreased single-nephron glomerular filtration rate (SNGFR) by 30%, the consequence of 10 and 35% reductions in the glomerular capillary hydrostatic pressure difference (delta P) and the single-nephron plasma flow (SNPF), respectively. Pre- and postglomerular vascular resistances increased. RNS during prostaglandin inhibition (indomethacin) resulted in a 70% reduction in SNGFR, secondary to 1) a further diminution in delta P and in SNPF, via heightened pre- and postglomerular vasoconstriction and 2) a marked decline in the glomerular ultrafiltration coefficient (LpA), from 0.058 +/- 0.006 to 0.027 +/- 0.002 nl.s-1.mmHg-1.g kidney wt-1 (P less than 0.005). Acute angiotensin II inhibition (MK-421 and [Sar1,Ala8]angiotensin II) in rats pretreated with indomethacin partially attenuated the effects of RNS on vascular resistances and therefore on delta P, SNPF, and SNGFR and prevented the reduction in LpA. Thus vasodilatory prostaglandins act as local modulators of both renal nerve and angiotensin II constrictive actions on glomeruli and renal microcirculation.

Sign in / Sign up

Export Citation Format

Share Document