Inhibition of nitric oxide synthesis attenuates pressure-induced natriuretic responses in anesthetized dogs

1993 ◽  
Vol 264 (1) ◽  
pp. F79-F87 ◽  
Author(s):  
D. S. Majid ◽  
A. Williams ◽  
L. G. Navar
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Synthesis Inhibition ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis

Inhibition of nitric oxide (NO) synthesis by intrarenal administration of nitro-L-arginine (NLA) leads to decreases in urinary sodium excretion (UNaV) in association with the increases in renal vascular resistance (RVR). In the present study, we examined the ability of the kidney to alter its sodium excretion in response to acute changes in renal arterial pressure (RAP) in anesthetized dogs before and during intrarenal infusion of NLA (50 micrograms.kg-1.min-1). NO synthesis inhibition in 11 dogs increased RVR by 32 +/- 4% and decreased renal blood flow (RBF) by 25 +/- 3%, outer cortical blood flow by 25 +/- 6%, urine flow by 37 +/- 14%, UNaV by 71 +/- 5%, and fractional excretion of sodium (FENa) by 71 +/- 4%. Glomerular filtration rate was not significantly changed during NLA infusion. As previously reported, there was suppression of the RBF autoregulation plateau during NO synthesis inhibition. In addition, there was a marked attenuation of urine flow and UNaV responses to reductions in RAP (150 to 75 mmHg), with significant reductions in the slopes of the relationships between RAP vs. UNaV and RAP vs. FENa during NLA infusion. Similar responses were observed in nine other dogs treated with the angiotensin receptor antagonist losartan, indicating that an augmented activity of the renin-angiotensin system is not responsible for attenuation of the slope of the pressure-natriuresis relationship during NLA infusion. These data suggest that NO may participate in the mediation of the pressure-natriuresis response.

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.

Suppression of blood flow autoregulation plateau during nitric oxide blockade in canine kidney

1992 ◽  
Vol 262 (1) ◽  
pp. F40-F46 ◽  
Author(s):  
D. S. Majid ◽  
L. G. Navar
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Enzyme Inhibitor ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Systemic Arterial Pressure ◽  
Linear Portion ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Renal Vascular

We examined the autoregulation of renal blood flow (RBF) and renal function in anesthetized dogs during nitro-L-arginine (NLA)-induced blockade of endothelium-derived nitric oxide (EDNO). Intrarenal infusion of NLA (50 micrograms.kg-1.min-1) increased systemic arterial pressure (AP) and renal vascular resistance (RVR). RBF decreased by 27 +/- 3%, but glomerular filtration rate remained unchanged. There were reductions in urine flow (24 +/- 5%), urinary sodium excretion (42 +/- 10%), and fractional excretion of sodium (40 +/- 11%). The vasodilatory responses to intrarenal injections of ATP (1, 5, 10 microM) were reversed, whereas such responses to doses (10, 50, 100 ng) of acetylcholine (ACh) were attenuated during NLA infusion. Indomethacin (5 mg/kg iv) treatment further reduced but did not completely abolish ACh-induced vasodilation, suggesting that factor(s) other than EDNO and prostaglandins may also mediate ACh-induced vasodilation in the kidney. Although there was a suppression of the plateau of the AP-RBF relationship with a rightward shift in the slope of the linear portion of the curve during EDNO blockade, the normal autoregulatory pattern remained intact. Similar responses were seen in dogs treated with the angiotensin-converting enzyme inhibitor, MK-422. These data indicate that EDNO contributes to the normally low renal vascular tone by influencing an autoregulation-independent component of RVR. However, the basic capability to adjust RVR (autoregulation-responsive component) in response to changes in AP is essentially autonomous from EDNO activity.

Antagonistic effect of theophylline on the adenosine-induced decreased in renin release

1984 ◽  
Vol 247 (2) ◽  
pp. F246-F251 ◽  
Author(s):  
W. S. Spielman
Keyword(s):  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Renal Cortex ◽  
Fractional Excretion ◽  
Antagonistic Effect ◽  
Renin Release ◽  
Detectable Effect ◽  
Fractional Sodium Excretion ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs

The action of theophylline on the adenosine-induced decrease in renin release was studied in anesthetized dogs. Adenosine inhibited renin release, decreased GFR and fractional sodium excretion, and decreased the concentration of angiotensin II in the renal lymph. Theophylline (5 mumol/min intrarenally) had no significant effect on GFR or RBF yet produced a significant increase in the release of renin and the fractional excretion of sodium. The intrarenal infusion of adenosine (3 X 10(-7) mol/min) during theophylline infusion produced no effect on GFR or RBF, but fractional sodium excretion and renin release were significantly decreased. Adenosine was infused at a lower dose (3 X 10(-8) mol/min) during theophylline (5 X 10(-6) mol/min) infusion in a second group of dogs. With the exception of fractional sodium excretion, all effects of adenosine were effectively antagonized by theophylline. Theophylline at 5 X 10(-6) mol/min, which stimulates renin release and effectively antagonizes the renal effects of adenosine, had no detectable effect on cAMP measured in renal cortex. Furthermore, no change in cortical cAMP was observed until theophylline was increased 50-fold over the dose effective in antagonizing adenosine. These findings demonstrate that theophylline, at concentrations having no effect on cortical cAMP, antagonizes the effect of adenosine on renin release. The results are also consistent with the view that theophylline stimulates renin release by a mechanism other than its action on cAMP.

Effect of intrarenal renin inhibition on renal hemodynamics and excretory function

1990 ◽  
Vol 259 (1) ◽  
pp. R7-R14 ◽  
Author(s):  
K. M. Verburg ◽  
J. R. Kadam ◽  
G. A. Young ◽  
S. H. Rosenberg ◽  
H. D. Kleinert
Keyword(s):  
Recovery Period ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Electrolyte Excretion ◽  
Angiotensin System ◽  
Excretory Function ◽  
Fractional Excretion Of Sodium ◽  
Renin Inhibition

This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin-angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of atrial natriuretic peptide in volume-expansion natriuresis

1986 ◽  
Vol 251 (2) ◽  
pp. R310-R313 ◽  
Author(s):  
T. R. Schwab ◽  
B. S. Edwards ◽  
D. M. Heublein ◽  
J. C. Burnett
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Urinary Sodium ◽  
Right Atrial ◽  
Fractional Excretion Of Sodium

Studies were performed to investigate the role of circulating atrial natriuretic peptide (ANP) in acute volume-expansion natriuresis. Sham-operated (SHAM, n = 6) and right atrial appendectomized (ATRX, n = 12) anesthetized rats underwent acute volume expansion with isoncotic albumin. After equilibration and control periods, volume expansion increased urine flow rate, urinary sodium excretion, fractional excretion of sodium, and circulating ANP. Absolute increases in urine flow rate (delta 46 +/- 4 SHAM; delta 25 +/- 5 microliter/min ATRX), urinary sodium excretion (delta 9.48 +/- 1.01 SHAM; delta 4.77 +/- 1.03 mueq/min ATRX), fractional excretion of sodium (delta 3.16 +/- 0.53 SHAM; delta 1.65 +/- 0.32% ATRX), and ANP (delta 303.3 +/- 35.9 SHAM; delta 156.6 +/- 26.0 pg/ml ATRX) were significantly reduced by right atrial appendectomy. No significant differences in mean arterial pressure, central venous pressure, or glomerular filtration rate during volume expansion were observed between groups. These studies support the hypothesis that right atrial appendectomy in the rat attenuates acute volume expansion-induced increases in circulating ANP and urinary sodium excretion and that the natriuresis of acute volume expansion is mediated in part by an increase in circulating ANP.

scholarly journals Interactions between nitric oxide and renal nerves on pressure-diuresis and natriuresis.

1998 ◽  
Vol 9 (9) ◽  
pp. 1588-1595
Author(s):  
M I Madrid ◽  
M G Salom ◽  
J Tornel ◽  
E López ◽  
F J Fenoy
Keyword(s):  
Nitric Oxide ◽  
Renal Denervation ◽  
Fractional Excretion ◽  
Renal Nerves ◽  
High Dose ◽  
Lower Baseline ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
High Doses ◽  
Pressure Natriuresis

The present study examined the effect of renal denervation on the impairment of the pressure-diuresis response produced by nitric oxide synthesis blockade. The experiments were performed in Inactin-anesthetized Munich-Wistar rats. The animals with innervated kidneys had lower baseline values of renal blood flow, GFR, sodium excretion (UNaV), and urine flow (V) than rats with denervated kidneys. Also, renal denervation shifted pressure-diuresis and natriuresis toward lower pressures. A low dose of N(omega)-nitro-L-arginine methyl esther (NAME, 3.7 nmol/kg per min) reduced UNaV and the fractional excretion of sodium (FENa) and blunted pressure-natriuresis only in rats with innervated kidneys, whereas it had no effects in rats with denervated kidneys. A medium dose of NAME (37 nmol/kg per min) lowered FENa only in rats with innervated kidneys. The administration of NAME (37 nmol/kg per min) blunted pressure-diuresis and natriuresis in kidneys with or without the renal nerves, but the effect was more pronounced in rats with innervated kidneys. A high dose of NAME (3.7 micromol + 185 nmol/kg per min) increased UNaV and FENa only in rats with innervated kidneys, whereas it reduced GFR, V, UnaV, and FENa in rats with denervated kidneys. However, pressure-natriuresis and diuresis were blunted by this high dose of NAME independently of the presence or absence of renal nerves. These results demonstrate that renal nerves potentiate the renal effects of low doses of NAME on renal function and pressure-diuresis and natriuresis. However, high doses of NAME abolish pressure-diuresis independently of renal nerves, and the natriuretic effect of NAME in innervated kidneys may be attributed to reflex inhibition of sympathetic tone due to the rise in arterial pressure.

Renal interstitial hydrostatic pressure and PGE2 in pressure natriuresis

1991 ◽  
Vol 260 (5) ◽  
pp. F643-F649 ◽  
Author(s):  
J. M. Gonzalez-Campoy ◽  
C. Long ◽  
D. Roberts ◽  
T. J. Berndt ◽  
J. C. Romero ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Blood Flows ◽  
Renal Perfusion Pressure ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis ◽  
Indomethacin Treatment

The present study tested the hypothesis that the presence of renal prostaglandin E2 (PGE2) is necessary for full natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during increased renal perfusion pressure (RPP). In control untreated pentobarbital-anesthetized dogs (n = 7), fractional excretion of sodium (FENa) was 1.17 +/- 0.48, 1.07 +/- 0.24, and 2.69 +/- 0.57% at RPP of 90, 122, and 148 mmHg, respectively. These changes in FENa were associated with effective renal blood flows (ERBF) of 1.43 +/- 0.20, 1.49 +/- 0.23, and 1.99 +/- 0.40 ml.min-1.g kidney wt-1, respectively. Similarly, glomerular filtration rate (GFR) was 0.53 +/- 0.10, 0.71 +/- 0.10, and 0.72 +/- 0.14 ml.min-1.g kidney wt-1, respectively. Treatment with indomethacin, a cyclooxygenase inhibitor, significantly lowered FENa to 0.45 +/- 0.13, 0.77 +/- 0.21, and 1.19 +/- 0.59% at RPP of 91, 121, and 146 mmHg, respectively. Additionally, indomethacin treatment lowered ERBF (0.51 +/- 0.15, 0.52 +/- 0.10, and 0.85 +/- 0.21 ml.min-1.g kidney wt-1) and GFR (0.28 +/- 0.09, 0.34 +/- 0.09, and 0.47 +/- 0.09 ml.min-1.g kidney wt-1) at low, middle, and high RPP, respectively. PGE2 replacement (n = 6) into renal artery at 0.01 microgram.min-1.kg body wt-1 returned FENa, ERBF, and GFR to control levels over the same range of RPP, whereas prostacyclin (PGI2) infusion (n = 7) at the same dose did not. RIHP was 4.2 +/- 1.2, 4.2 + 0.5, and 7.5 +/- 1.7 mmHg with increasing RPP in control untreated group and increased to similar levels with indomethacin treatment and during PGE2 or PGI2 replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of renal perfusion pressure on renal interstitial hydrostatic pressure in rats

1989 ◽  
Vol 256 (1) ◽  
pp. F165-F170 ◽  
Author(s):  
A. A. Khraibi ◽  
J. A. Haas ◽  
F. G. Knox
Keyword(s):  
Hydrostatic Pressure ◽  
Flow Rate ◽  
Sodium Excretion ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Urine Flow ◽  
Polyethylene Matrix ◽  
Renal Perfusion Pressure ◽  
Fractional Excretion Of Sodium

The purpose of this study was to investigate the hypothesis that changes in renal perfusion pressure may be transmitted to the renal interstitium and cause alterations in renal interstitial hydrostatic pressure and sodium excretion. A method that utilizes a chronically implanted polyethylene matrix that allows for direct continuous measurement of renal interstitial hydrostatic pressure, and agrees well with subcapsular measurement in rats, was developed. Renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate were 3.0 +/- 0.3 mmHg, 0.35 +/- 0.13%, and 19.44 +/- 3.00 microliter/min, respectively, when renal perfusion pressure was 101 +/- 0.8 mmHg. When renal perfusion pressure was increased to 123 +/- 0.9 mmHg renal interstitial hydrostatic pressure, fractional excretion of sodium, and urine flow rate increased significantly to 5.8 +/- 0.6 mmHg, 1.29 +/- 0.29%, and 50.76 +/- 8.83 microliter/min, respectively, in anesthetized male Sprague-Dawley rats. These changes occur despite a well-autoregulated glomerular filtration rate and renal blood flow. In conclusion, increasing renal perfusion pressure caused a significant increase in renal interstitial hydrostatic pressure as measured directly by the implanted polyethylene matrix method and was associated with a significant increase in sodium excretion.

scholarly journals Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat.

1993 ◽  
Vol 4 (4) ◽  
pp. 1046-1053 ◽  
Author(s):  
T Takenaka ◽  
K D Mitchell ◽  
L G Navar
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Urine Flow ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonist ◽  
Synthesis Inhibition ◽  
Excretory Function ◽  
Suprarenal Aorta ◽  
Control Versus

This study was performed to evaluate the contribution of angiotensin II to the effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and excretory function in rats. Intravenous infusion of N omega-nitro-L-arginine (NLA; 20 micrograms/100 g.min) increased renal arterial pressure (RAP) from 128 +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P < 0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/- 1 to 135 +/- 2 mm Hg; P < 0.05) and decreased RBF by 42 +/- 3% (P < 0.05). However, NLA did not decrease GFR in the losartan-treated rats. As in the control rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2 (control) versus 127 +/- 2 mm Hg (NLA+CL)). NO synthesis inhibition decreased urine flow and sodium excretion (P < 0.05, in both cases). However, during blockade of AT1 receptors, NLA infusion failed to decrease urine flow and sodium excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm Hg (NLA+CL)).(ABSTRACT TRUNCATED AT 250 WORDS)

Renoprotective effects of nitric oxide in angiotensin II-induced hypertension in the rat

1998 ◽  
Vol 274 (5) ◽  
pp. F876-F882 ◽  
Author(s):  
So Yeon Chin ◽  
Chi-Tarng Wang ◽  
Dewan S. A. Majid ◽  
L. Gabriel Navar
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Absolute Increase ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium

Experiments were performed in anesthetized male Sprague-Dawley rats to determine whether increased nitric oxide (NO) activity during the development of hypertension exerts a protective effect on renal cortical blood flow (CBF) and medullary blood flow (MBF). The effects of acute NO synthase inhibition on renal function and on CBF and MBF, measured by laser-Doppler flow probes, were evaluated in control and ANG II-infused hypertensive rats, prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days. In normotensive rats ( n = 8), intravenous infusion of N ω-nitro-l-arginine (NLA; 20 μg ⋅ 100 g−1 ⋅ min−1) decreased CBF by 21 ± 4% and MBF by 49 ± 8% and increased blood pressure from 118 ± 1 to 140 ± 2 mmHg. In ANG II-infused rats ( n = 7), CBF and MBF decreased by 46 ± 5% and 25 ± 6%, respectively, during infusion of NLA. Arterial pressure increased from 160 ± 5 to 197 ± 7 mmHg, which was a greater absolute increase than in normotensive controls. Basal renal blood flow (RBF), estimated from p-aminohippurate clearance and hematocrit, was similar in both the control (6.0 ± 0.5 ml ⋅ min−1 ⋅ g−1) and hypertensive (6.0 ± 0.6 ml ⋅ min−1 ⋅ g−1) rats. However, NLA-induced reductions in RBF averaged 60 ± 5% in the hypertensive rats, compared with 31 ± 9% observed in control rats. GFR in control (0.97 ± 0.03 ml ⋅ min−1 ⋅ g−1) and hypertensive rats (0.78 ± 0.12 ml ⋅ min−1 ⋅ g−1) decreased to a similar extent during the first 30-min period of NLA infusion. GFR returned toward control levels in control rats; in contrast, GFR remained significantly decreased in the ANG II-infused rats (0.58 ± 0.11 ml ⋅ min−1 ⋅ g−1). Basal urinary sodium excretion (0.2 ± 0.08 μeq ⋅ min−1 ⋅ g−1), fractional excretion of sodium (0.3 ± 0.13%), and urine flow (4.9 ± 0.39 μl ⋅ min−1 ⋅ g−1) in hypertensive rats did not increase significantly after NLA treatment as occurred in normotensive controls. These data suggest that a compensatory increase in nitric oxide activity partially counteracts the vasoconstrictor influence of elevated ANG II levels to regulate renal hemodynamics and maintain cortical perfusion in the renal circulation.

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