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.

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.

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.

Role of renal interstitial hydrostatic pressure in natriuresis of systemic nitric oxide inhibition

1993 ◽  
Vol 264 (3) ◽  
pp. F411-F414 ◽  
Author(s):  
J. A. Haas ◽  
A. A. Khraibi ◽  
M. A. Perrella ◽  
F. G. Knox
Keyword(s):  
Nitric Oxide ◽  
Hydrostatic Pressure ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Significant Rise ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Suprarenal Aorta ◽  
Fractional Excretion Of Sodium

Systemic inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 micrograms.kg-1 x min-1 continuous infusion) increased RPP (delta+ 14 +/- 1 mmHg), RIHP (delta+ 3.6 +/- 0.7 mmHg), and fractional excretion of sodium (FENa; delta 2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FENa did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FENa was not significantly increased (delta+ 0.68 +/- 0.36%, not significant), despite a significant rise in RPP (delta+ 18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FENa. Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FENa. These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA.

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.

Renal vascular and excretory responses to prostaglandin endoperoxides in the dog

1979 ◽  
Vol 236 (3) ◽  
pp. H427-H433
Author(s):  
J. A. Oliver ◽  
R. R. Sciacca ◽  
P. J. Cannon
Keyword(s):  
Blood Flow ◽  
Renal Artery ◽  
Renal Blood Flow ◽  
Biologically Active ◽  
Direct Effects ◽  
Cortical Areas ◽  
Anesthetized Dogs ◽  
Renal Vascular ◽  
Higher Doses

To determine whether the prostaglandin endoperoxides PGG2 and PGH2 have direct effects in the kidney, PGG2 and PGH2 were administered into the renal artery of anesthetized dogs and their effects were compared to those of PGE2. Like PGE2, PGG2 and PGH2 induced a dose-related renal vasodilation. A 50% increase in the renal blood flow was observed with 0.05 microgram/kg body wt of PGE2 and with four- and sixfold higher doses of PGH2 and PGG2, respectively. Infusion of all three compounds at doses inducing a 50% increase in the renal blood flow resulted in 1) increases in blood flow to all cortical areas, with the greatest increase occurring in the juxtamedullary area, 2) diuresis with no change in the glomerular filtration rate, and 3) natriuresis and kaliuresis. In vitro incubation of PGH2, a maneuver known to result in its conversion to other prostaglandins, had no influence on its renal effects. The data indicate that PGH2 and PGG2 are biologically active when infused into the renal artery of the anesthetized dog and suggest that the endoperoxides exert their effects after bioconversion to other prostaglandins.

Renal vascular response to amino acids: effect of pancreatectomy

1990 ◽  
Vol 258 (5) ◽  
pp. F1154-F1163 ◽  
Author(s):  
A. J. Premen ◽  
D. A. Powell ◽  
R. G. Carroll ◽  
D. E. Dobbins
Keyword(s):  
Amino Acids ◽  
Blood Flow ◽  
Filtration Rate ◽  
Plasma Glucagon ◽  
Vascular Response ◽  
Incremental Change ◽  
Renal Hemodynamic ◽  
Anesthetized Dogs ◽  
Arterial Plasma ◽  
Renal Vascular

We ascertained the importance of glucagon in modulating the renal hemodynamic response to amino acid (AA) infusion in anesthetized dogs. In controls (n = 6), AAs (L-serine, alanine, and proline; 0.051 mmol.kg-1.min-1 iv) elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by 35 and 34%, respectively, while elevating arterial plasma glucagon-like immunoreactivity (AGLI) by 96 pmol/l. In control pancreatectomized (PX) dogs (n = 6), all parameters remained at control values over 2 h. In PX dogs, AAs (n = 6) failed to reproduce the renal hemodynamic and AGLI responses elicited by AAs in controls. In PX dogs infused with AAs, replacement of AGLI (n = 6) to an incremental plasma level of 111 pmol/l, a level no different than that produced by AAs in controls, elevated RBF and GFR by 25 and 26.5%, respectively. These hemodynamic responses were 71 and 78%, respectively, of the total responses elicited by AAs in controls. In PX dogs infused with glucagon alone (0.86 pmol.kg-1.min-1; n = 6), an incremental change in AGLI of 112 pmol/l was accompanied by only small increases in RBF and GFR (9%). These data suggest the importance of glucagon in modulating the renal hyperemia and hyperfiltration ascribed to AA infusion in anesthetized dogs.

Direct renal interstitial volume expansion causes exaggerated natriuresis in SHR

1991 ◽  
Vol 261 (4) ◽  
pp. F567-F570 ◽  
Author(s):  
A. A. Khraibi
Keyword(s):  
Volume Expansion ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Renal Interstitium ◽  
Time Control ◽  
Arterial Blood ◽  
Interstitial Volume ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto ◽  
Second Period

In Okamoto spontaneously hypertensive rats (SHR), elevated arterial blood pressure is not transmitted to the renal interstitium, and therefore pressure natriuretic and diuretic responses are attenuated. The objective of this study was to determine the effect of increasing renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion (DRIVE) on natriuresis and diuresis of SHR and Wistar-Kyoto rats (WKY). Unilateral nephrectomy and implantation of two polyethylene (PE) matrices were performed 3-4 wk before the acute experiment. Four groups of rats, two experimental and two time control, were used. A control clearance period was taken in all groups. In experimental groups and at the beginning and middle of the second period DRIVE was accomplished by bolus injection of a solution of 2.5% human albumin in saline directly into interstitium through one of the PE matrices. In time-control groups saline was infused in renal interstitium at the beginning of the second period. The second PE matrix was used to continuously measure RIHP in all groups. In experimental groups, DRIVE produced a significant increase in RIHP from 3.8 +/- 0.4 to 5.7 +/- 0.8 mmHg (P less than 0.05) in SHR and 4.3 +/- 0.4 to 7.1 +/- 0.5 mmHg (P less than 0.05) in WKY. In both groups the significant increase in RIHP was associated with significant increases in urinary sodium excretion (UNaV), fractional excretion of sodium (FENa), and urine flow rate (V).(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide as a regulator of adrenal blood flow

1993 ◽  
Vol 264 (2) ◽  
pp. H464-H469 ◽  
Author(s):  
M. J. Breslow ◽  
J. R. Tobin ◽  
D. S. Bredt ◽  
C. D. Ferris ◽  
S. H. Snyder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Neural Control ◽  
Splanchnic Nerve ◽  
No Synthase ◽  
Catecholamine Secretion ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor ◽  
Splanchnic Nerve Stimulation

To determine whether nitric oxide (NO) is involved in adrenal medullary vasodilation during splanchnic nerve stimulation (NS)-induced catecholamine secretion, blood flow (Q) and secretory responses were measured in pentobarbital-anesthetized dogs before and after administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (40 mg/kg iv over 5 min, followed by 40 mg.kg-1.h-1) reduced NO synthase activity of medullary and cortical homogenates from 5.2 +/- 0.3 to 0.7 +/- 0.1 pmol.min-1.mg protein-1 and from 1.2 +/- 0.2 pmol.min-1.mg protein-1 to undetectable levels, respectively. L-NAME reduced resting medullary and cortical Q by 42 and 60%, respectively. NS before L-NAME increased medullary Q from 181 +/- 16 to 937 +/- 159 ml.min-1.100 g-1 and epinephrine secretion from 1.9 +/- 0.8 to 781 +/- 331 ng/min. NS after L-NAME had no effect on medullary Q (103 +/- 14 vs. 188 +/- 34 ml.min-1.100 g-1), while epinephrine secretion increased to the same extent as in control animals (1.9 +/- 0.7 vs. 576 +/- 250 ng/min). L-NAME also unmasked NS-induced cortical vasoconstriction; cortical Q decreased from 96 +/- 8 to 50 +/- 5 ml.min-1.100 g-1. Administration of hexamethonium (30 mg/kg iv), a nicotinic receptor antagonist, reduced NS-induced epinephrine secretion by 90%. These data suggest independent neural control of medullary Q and catecholamine secretion, the former by NO and the latter by acetylcholine.

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.

20-HETE-mediated vasoconstriction by hemoglobin-O2 carrier in Sprague-Dawley but not Wistar rats

2005 ◽  
Vol 98 (3) ◽  
pp. 772-779 ◽  
Author(s):  
Andrew D. Baines ◽  
Patrick Ho
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Wistar Rats ◽  
Filtration Rate ◽  
Blood Substitutes ◽  
Sprague Dawley ◽  
Ringer Lactate ◽  
Sd Rats ◽  
Renal Vascular

Hypothetically either decreased nitric oxide (NO) or increased O2 could initiate 20-HETE-mediated vasoconstriction associated with hemoglobin-based blood substitutes (HBOC). To test this hypothesis, we infused Tm-Hb, an HBOC with low O2 affinity, into isoflurane-anesthetized Wistar (W) and Sprague-Dawley (SD) rats after exchanging 20% of their blood with Ringer lactate. For comparison we infused an equal amount of BSA or BSA with NG-nitro-l-arginine methyl ester (BSA+NAME). Tm-Hb increased blood pressure (BP) and renal vascular resistance (RVR) equally in W and SD rats. Renal blood flow (RBF; Doppler ultrasound) decreased. BSA decreased RVR and raised glomerular filtration rate. BSA+NAME raised BP, RVR, and GFR. HET0016, an inhibitor of 20-HETE production, blunted BP and RVR responses to Tm-Hb and BSA+NAME in SD but not W rats. Arterial O2 content with BSA was lower than with Tm-Hb but O2 delivery was 60% higher with BSA because of higher RBF. BSA raised Po2 (Oxylite) in cortex and medulla and reduced RVR. Tm-Hb decreased Po2 and increased RVR. Switching rats from breathing air to 100% O2 raised intrarenal Po2 two- to threefold and increased BP and RVR. HET0016 did not alter hyperoxic responses. In conclusion, 20-HETE contributes to vasoconstriction by Tm-Hb in SD but not in W rats, and increased 20-HETE activity results primarily from decreased NO.

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