scholarly journals Nitric oxide blunts myogenic autoregulation in rat renal but not skeletal muscle circulation via tubuloglomerular feedback

2005 ◽  
Vol 569 (3) ◽  
pp. 959-974 ◽  
Author(s):  
Armin Just ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Tubuloglomerular Feedback ◽  
Muscle Circulation

Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action

Diabetes ◽  
1997 ◽  
Vol 46 (11) ◽  
pp. 1691-1700 ◽  
Author(s):  
S. Kapur ◽  
S. Bedard ◽  
B. Marcotte ◽  
C. H. Cote ◽  
A. Marette
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Insulin Action ◽  
Oxide Synthase

Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells

1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Ionic Composition ◽  
Juxtaglomerular Apparatus ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Rapid Reduction ◽  
No Release

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

2006 ◽  
Vol 291 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
Zhengrong Guan ◽  
Glenda Gobé ◽  
Desley Willgoss ◽  
Zoltán H. Endre
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Endothelial Nitric Oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U) or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 μM furosemide. Autoregulation was enhanced by Nω-nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

The effect of the nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells

Nitric Oxide ◽  
2009 ◽  
Vol 21 (2) ◽  
pp. 126-131 ◽  
Author(s):  
Darren C. Henstridge ◽  
Brian G. Drew ◽  
Melissa F. Formosa ◽  
Alaina K. Natoli ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Sodium Nitroprusside ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Nitric Oxide Donor

scholarly journals Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

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