scholarly journals Angiotensin II blockade causes acute renal failure in eNOS-deficient mice

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S199-S203 ◽  
Author(s):  
Jürgen Schnermann ◽  
Yuning G Huang ◽  
Josie P Briggs
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Knockout Mice ◽  
Renal Vascular Resistance ◽  
Wild Type ◽  
Arteriolar Tone ◽  
Renal Vascular ◽  
Deficient Mice

Compared with wild-type mice, adult endothelial nitric oxide synthase (eNOS) knockout mice (eight months of age) have increased blood pressure (BP) (126±9 mmHg vs. 100±4 mmHg), and an increased renal vascular resistance (155±16 vs. 65±4 mmHg.min/ml). Renal vascular resistance responses to i.v. administration of noradrenaline were markedly enhanced in eNOS knockout mice. Glomerular filtration rate (GFR) of anaesthetised eNOS -/- mice was 324±57 µl/min gKW, significantly lower than the GFR of 761±126 µl/min.gKW in wild-type mice. AT1-receptor blockade with i.v. candesartan (1—1.5 mg/kg) reduced arterial blood pressure and renal vascular resistance, and increased renal blood flow (RBF) to about the same extent in wild-type and eNOS -/- mice. Candesartan did not alter GFR in wild-type mice (761±126 vs. 720±95 µl/min.gKW), but caused a marked decrease in GFR in eNOS -/- mice (324.5±75.2 vs. 77±18 µl/min.gKW). A similar reduction in GFR of eNOS deficient mice was also caused by angiotensin-converting enzyme (ACE) inhibition. Afferent arteriolar granularity, a measure of renal renin expression, was found to be reduced in eNOS -/- compared with wild-type mice. In chronically eNOS-deficient mice, angiotensin II (Ang II) is critical for maintaining glomerular filtration pressure and GFR, presumably through its effect on efferent arteriolar tone.

Reduced autoregulatory effectiveness in adenosine 1 receptor-deficient mice

2006 ◽  
Vol 290 (4) ◽  
pp. F888-F891 ◽  
Author(s):  
S. Hashimoto ◽  
Y. Huang ◽  
J. Briggs ◽  
J. Schnermann
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Blood Pressure Reduction ◽  
Renal Perfusion ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Wild Type ◽  
Before And After ◽  
Renal Vascular ◽  
Deficient Mice

Adjustments of renal vascular resistance in response to changes in blood pressure are mediated by an interplay between the myocyte-inherent myogenic and the kidney-specific tubuloglomerular feedback (TGF) mechanisms. Using mice with deletion of the A1 adenosine receptor (A1AR) gene, we tested the prediction that the absence of TGF, previously established to result from A1AR deficiency, is associated with a reduction in the efficiency of autoregulation. In anesthetized wild-type (A1AR+/+) and A1AR-deficient mice (A1AR−/−), glomerular filtration rate (GFR) and renal blood flow (RBF) were determined before and after reducing renal perfusion pressure through a suprarenal aortic clamp. In response to a blood pressure reduction by 15.9 ± 1.34 mmHg in A1AR−/− ( n = 9) and by 14.2 ± 0.9 mmHg in A1AR+/+ mice ( n = 8; P = 0.31), GFR fell by 187.9 ± 37 μl/min and by 72.3 ± 10 μl/min in A1AR−/− and A1AR+/+ mice, respectively ( P = 0.013). Similarly, with pressure reductions of 14.8 ± 1.1 and 13.3 ± 1.5 mmHg in A1AR−/− ( n = 9) and wild-type mice ( n = 8), respectively ( P = 0.43), RBF fell by 0.17 ± 0.02 ml/min in A1AR−/− mice and by only 0.08 ± 0.02 ml/min in wild-type animals ( P = 0.0039). Autoregulatory indexes for both GFR and RBF were significantly higher in A1AR−/− compared with A1AR+/+ mice, indicating reduced regulatory responsiveness in the knockout animals. We conclude that autoregulation of renal vascular resistance is less complete in A1AR-deficient mice, an effect that is presumably related to absence of TGF regulation in these animals.

Renal vasodilatation after inhibition of renin or converting enzyme in marmoset

1986 ◽  
Vol 251 (5) ◽  
pp. H897-H902
Author(s):  
D. Neisius ◽  
J. M. Wood ◽  
K. G. Hofbauer
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Enzyme Inhibitor ◽  
Renal Vascular Resistance ◽  
Converting Enzyme ◽  
Renin Inhibition ◽  
Renal Vascular

The relative importance of angiotensin II for the renal vasodilatory response after converting-enzyme inhibition was evaluated by a comparison of the effects of converting-enzyme and renin inhibition on renal vascular resistance. Renal, mesenteric, and hindquarter blood flows were measured with chronically implanted ultrasonic-pulsed Doppler flow probes in conscious, mildly volume-depleted marmosets after administration of a converting-enzyme inhibitor (enalaprilat, 2 mg/kg iv), a synthetic renin inhibitor (CGP 29,287, 1 mg/kg iv), or a renin-inhibitory monoclonal antibody (R-3-36-16, 0.1 mg/kg iv). Enalaprilat reduced blood pressure (-16 +/- 4 mmHg, n = 6) and induced a selective increase in renal blood flow (27 +/- 8%, n = 6). CGP 29,287 and R-3-36-16 induced comparable reductions in blood pressure (-16 +/- 4 mmHg, n = 6 and -20 +/- 4 mmHg, n = 5, respectively) and selective increases in renal blood flow (36 +/- 12%, n = 6 and 34 +/- 16%, n = 4, respectively). The decrease in renal vascular resistance was of similar magnitude for all of the inhibitors (enalaprilat -28 +/- 3%, CGP 29,287 -32 +/- 6%; and R-3-36-16 -33 +/- 7%). These results indicate that the renal vasodilatation induced after converting-enzyme or renin inhibition is mainly due to decreased formation of angiotensin II.

Absence of Adrenergic Mediation of Agonist Response to [Sar1,Ala8]Angiotensin II in Conscious Normotensive and Hypertensive Dogs

1979 ◽  
Vol 57 (1) ◽  
pp. 71-81 ◽  
Author(s):  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Intravenous Infusion ◽  
Direct Action ◽  
Renal Vascular Resistance ◽  
Angiotensin Receptors ◽  
Conscious Dog ◽  
Renal Vascular

1. In the conscious normotensive and two-kidney Goldblatt hypertensive dog a transient agonist response to the intravenous infusion of saralasin (1 μg min−1 kg−1) was manifested by a small increase in blood pressure (6–12 mmHg) and 28–30% increase in renal vascular resistance. 2. These increases in blood pressure and renal vascular resistance were unaffected by administration of either phentolamine or guanethidine. 3. The agonist response in the conscious dog is most likely accounted for by a direct action of saralasin on vascular angiotensin receptors.

scholarly journals Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis

2010 ◽  
Vol 298 (4) ◽  
pp. R1050-R1055 ◽  
Author(s):  
Jazmin M. Perez-Rojas ◽  
Kamal M. Kassem ◽  
William H. Beierwaltes ◽  
Jeffrey L. Garvin ◽  
Marcela Herrera
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Peripheral Resistance ◽  
Extracellular Fluid ◽  
Wild Type ◽  
Water Excretion ◽  
Volume Load ◽  
Renal Vascular

Extracellular fluid volume is highly regulated, at least in part, by peripheral resistance and renal function. Nitric oxide (NO) produced by NO synthase type 3 (NOS 3) in the nonrenal vasculature may promote fluid retention by reducing systemic vascular resistance and arterial pressure. In contrast, NO produced by renal NOS 3 promotes water excretion by reducing renal vascular resistance, increasing glomerular filtration, and inhibiting reabsorption along the nephron. Thus, the net effect of NO from NOS 3 on urinary volume (UV) is unclear. We hypothesized that NO produced by NOS 3 promotes water excretion primarily due to renal tubular effects. We gave conscious wild-type and NOS 3 −/− mice an acute volume load and measured UV, blood pressure, plasma renin concentration (PRC), Na+, vasopressin, and urinary Na+ and creatinine concentrations. To give the acute volume load, we trained mice to drink a large volume of water while in metabolic cages. On the day of the experiment, water was replaced with 1% sucrose, and mice had access to it for 1 h. Volume intake was similar in both groups. Over 3 h, wild-type mice excreted 62 ± 10% of the volume load, but NOS 3 −/− excreted only 42 ± 5% ( P < 0.05). Blood pressure in NOS 3 −/− was 118 ± 3 compared with 110 ± 2 mmHg in wild-type mice ( P < 0.05), but it did not change following volume load in either strain. PRC, vasopressin, and glomerular filtration rate were similar between groups. Urinary Na+ excretion was 49.3 ± 7.0 in wild-type vs. 37.8 ± 6.4 μmol/3 h in NOS 3 −/− mice ( P < 0.05). Bumetanide administration eliminated the difference in volume excretion between wild-type and NOS 3 −/− mice. We conclude that 1) NO produced by NOS 3 promotes water and Na+ excretion and 2) the renal epithelial actions of NO produced by NOS 3 supersede the systemic and renal vascular actions.

Endothelial nitric oxide synthase is predominantly involved in angiotensin II modulation of renal vascular resistance and norepinephrine release

2008 ◽  
Vol 294 (2) ◽  
pp. R421-R428 ◽  
Author(s):  
Johannes Stegbauer ◽  
Yvonne Kuczka ◽  
Oliver Vonend ◽  
Ivo Quack ◽  
Lorenz Sellin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Wild Type ◽  
Norepinephrine Release ◽  
Renal Nerve ◽  
Sympathetic Neurotransmission ◽  
Pressor Responses ◽  
Renal Vascular

Nitric oxide (NO) is mainly generated by endothelial NO synthase (eNOS) or neuronal NOS (nNOS). Recent studies indicate that angiotensin II generates NO release, which modulates renal vascular resistance and sympathetic neurotransmission. Experiments in wild-type [eNOS(+/+) and nNOS(+/+)], eNOS-deficient [eNOS(−/−)], and nNOS-deficient [nNOS(−/−)] mice were performed to determine which NOS isoform is involved. Isolated mice kidneys were perfused with Krebs-Henseleit solution. Endogenous norepinephrine release was measured by HPLC. Angiotensin II dose dependently increased renal vascular resistance in all mice species. EC50 and maximal pressor responses to angiotensin II were greater in eNOS(−/−) than in nNOS(−/−) and smaller in wild-type mice. The nonselective NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME; 0.3 mM) enhanced angiotensin II-induced pressor responses in nNOS(−/−) and wild-type mice but not in eNOS(−/−) mice. In nNOS(+/+) mice, 7-nitroindazole monosodium salt (7-NINA; 0.3 mM), a selective nNOS inhibitor, enhanced angiotensin II-induced pressor responses slightly. Angiotensin II-enhanced renal nerve stimulation induced norepinephrine release in all species. l-NAME (0.3 mM) reduced angiotensin II-mediated facilitation of norepinephrine release in nNOS(−/−) and wild-type mice but not in eNOS(−/−) mice. 7-NINA failed to modulate norepinephrine release in nNOS(+/+) mice. (4-Chlorophrnylthio)guanosine-3′, 5′-cyclic monophosphate (0.1 nM) increased norepinephrine release. mRNA expression of eNOS, nNOS, and inducible NOS did not differ between mice strains. In conclusion, angiotensin II-mediated effects on renal vascular resistance and sympathetic neurotransmission are modulated by NO in mice. These effects are mediated by eNOS and nNOS, but NO derived from eNOS dominates. Only NO derived from eNOS seems to modulate angiotensin II-mediated renal norepinephrine release.

Limb tourniquet and intramuscular clostridial toxin effects on renal function

1962 ◽  
Vol 17 (1) ◽  
pp. 83-86 ◽  
Author(s):  
James F. Nickel ◽  
John A. Gagnon ◽  
Leonard Levine
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Sodium Excretion ◽  
Renal Vascular Resistance ◽  
Arterial Blood ◽  
Hind Limbs ◽  
Renal Changes ◽  
Anesthetized Dogs ◽  
Peripheral Trauma ◽  
Renal Vascular

Eight anesthetized dogs, given Clostridium perfringens type A toxic filtrate into the hind-limb muscles, showed severe spreading edema, hemoconcentration, marked reduction in para-aminohippurate (PAH) and creatinine clearances, and a rise in the renal vascular resistance. In the first 4 hr sodium excretion fell sharply, and mean arterial blood pressure, slightly. In eight similar dogs venous-occlusive pneumatic tourniquets were applied high on both hind limbs for 90 min. Edema was localized and minimal. Hematocrit was unchanged. PAH and creatinine clearances were extremely low in the second 30-min period of the occlusion but had risen somewhat in the last 30-min period. Sodium excretion was greatly reduced. Arterial pressure and vascular resistance rose very significantly. Upon removal of the tourniquets, PAH and creatinine clearances, blood pressure, and renal vascular resistance returned toward normal. Sodium excretion continued to fall. In many respects the renal changes resulting from two different forms of peripheral trauma are similar. Submitted on August 14, 1959

‘Structural Autoregulation’ of the Preglomerular/Postglomerular Resistance Ratio and Hence of Glomerular Filtration Rate in the Clipped (Low Pressure) Kidney in Two-Kidney, One-Clip Renal Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 359s-362s ◽  
Author(s):  
Gunnar Göthberg ◽  
Björn Folkow
Keyword(s):  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Renal Hypertension ◽  
Low Pressure ◽  
Resistance Ratio ◽  
Renal Vascular Resistance ◽  
Kidney Weight ◽  
Renal Vascular ◽  
Filtration Capacity ◽  
Renal Hypertensive Rats

1. The chronically clipped left kidneys of two-kidney, one-clip renal hypertensive rats (duration >4 weeks) showed a 45% decrease in organ weight compared with left kidneys from age-matched normotensive Wistar rats (0.59 ± 0.09 vs 1.12 ± 0.05 g). 2. These ‘low-pressure’ kidneys exhibited at maximal vasodilatation a 40% decrease in total renal vascular resistance per unit kidney weight, a reduction in the preglomerular/postglomerular resistance ratio (filtration curve displaced markedly to the left of the control), though combined with some decrease in maximal glomerular filtration capacity. 3. Thus the vascular bed of chronically clipped low-pressure kidneys displays a ‘downward’ structural autoregulation, which by lowering of the total renal vascular resistance and the preglomerular/postglomerular resistance ratio serves to maintain blood flow and to increase filtration pressure thereby raising the filtration fraction.

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