Effects of glyceryl trinitrate, nitroprusside and nitric oxide on arterial, venous and capillary functions in cat skeletal muscle in vivo

1994 ◽  
Vol 152 (1) ◽  
pp. 93-105 ◽  
Author(s):  
U. EKELUND
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Glyceryl Trinitrate

In Vivo Spin Trapping of Glyceryl Trinitrate–Derived Nitric Oxide in Rabbit Blood Vessels and Organs

Circulation ◽  
1995 ◽  
Vol 92 (7) ◽  
pp. 1876-1882 ◽  
Author(s):  
Alexander Mülsch ◽  
Peter Mordvintcev ◽  
Eberhard Bassenge ◽  
Frank Jung ◽  
Bernd Clement ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Blood Vessels ◽  
Spin Trapping ◽  
Rabbit Blood

Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle

2007 ◽  
Vol 293 (4) ◽  
pp. E1062-E1068 ◽  
Author(s):  
Vitor A. Lira ◽  
Quinlyn A. Soltow ◽  
Jodi H. D. Long ◽  
Jenna L. Betters ◽  
Jeff E. Sellman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Glucose Transporter ◽  
No Donor ◽  
Ampk Signaling ◽  
L6 Myotubes ◽  
Glut4 Expression ◽  
Compound C ◽  
Cgmp Analog

Nitric oxide (NO) and 5′-AMP-activated protein kinase (AMPK) are involved in glucose transport and mitochondrial biogenesis in skeletal muscle. Here, we examined whether NO regulates the expression of the major glucose transporter in muscle (GLUT4) and whether it influences AMPK-induced upregulation of GLUT4. At low levels, the NO donor S-nitroso- N-penicillamine (SNAP, 1 and 10 μM) significantly increased GLUT4 mRNA (∼3-fold; P < 0.05) in L6 myotubes, and cotreatment with the AMPK inhibitor compound C ablated this effect. The cGMP analog 8-bromo-cGMP (8-Br-cGMP, 2 mM) increased GLUT4 mRNA by ∼50% ( P < 0.05). GLUT4 protein expression was elevated 40% by 2 days treatment with 8-Br-cGMP, whereas 6 days treatment with 10 μM SNAP increased GLUT4 expression by 65%. Cotreatment of cultures with the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one prevented the SNAP-induced increase in GLUT4 protein. SNAP (10 μM) also induced significant phosphorylation of α-AMPK and acetyl-CoA carboxylase and translocation of phosphorylated α-AMPK to the nucleus. Furthermore, L6 myotubes exposed to 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 16 h presented an approximately ninefold increase in GLUT4 mRNA, whereas cotreatment with the non-isoform-specific NOS inhibitor NG-nitro-l-arginine methyl ester, prevented ∼70% of this effect. In vivo, GLUT4 mRNA was increased 1.8-fold in the rat plantaris muscle 12 h after AICAR injection, and this induction was reduced by ∼50% in animals cotreated with the neuronal and inducible nitric oxide synthases selective inhibitor 1-(2-trifluoromethyl-phenyl)-imidazole. We conclude that, in skeletal muscle, NO increases GLUT4 expression via a cGMP- and AMPK-dependent mechanism. The data are consistent with a role for NO in the regulation of AMPK, possibly via control of cellular activity of AMPK kinases and/or AMPK phosphatases.

scholarly journals Opposite Reactivity of Meningeal versus Cortical Microvessels to the Nitric Oxide Donor Glyceryl Trinitrate Evaluated In Vivo with Two-Photon Imaging

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89699 ◽  
Author(s):  
Evgeny Pryazhnikov ◽  
Mikhail Kislin ◽  
Marina Tibeykina ◽  
Dmytro Toptunov ◽  
Anna Ptukha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Nitric Oxide Donor ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin

2003 ◽  
Vol 285 (1) ◽  
pp. E123-E129 ◽  
Author(s):  
M. A. Vincent ◽  
E. J. Barrett ◽  
J. R. Lindner ◽  
M. G. Clark ◽  
S. Rattigan
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Glucose Disposal ◽  
Total Blood ◽  
Artery Flow ◽  
Microvascular Recruitment ◽  
Total Blood Flow

We examined the effects of inhibiting nitric oxide synthase with Nω-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU·min-1·kg-1) significantly increased hindlimb total blood flow (0.69 ± 0.02 to 1.22 ± 0.11 ml/min, P < 0.05), glucose uptake (0.27 ± 0.05 to 0.95 ± 0.08 μmol/min, P < 0.05), 1-MX uptake (5.0 ± 0.5 to 8.5 ± 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 ± 1.6 to 15.0 ± 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% ( P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Endothelium-Dependent Modulation of Responses to Endothelin-1 in Human Veins

1993 ◽  
Vol 84 (4) ◽  
pp. 427-433 ◽  
Author(s):  
William G. Haynes ◽  
David J. Webb
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Low Dose ◽  
Nitric Oxide Production ◽  
Irreversible Inhibitor ◽  
Endothelin 1 ◽  
Oxide Production ◽  
Dorsal Hand ◽  
Dorsal Hand Vein

1. We have investigated whether local vascular production of nitric oxide or prostacyclin regulates venoconstriction induced by the endothelium-derived peptide, endothelin-1, in vivo in man. 2. Six healthy subjects received local dorsal hand vein infusion of endothelin-1 for 60 min alone or, on two separate occasions, co-infused with the donator of nitric oxide, glyceryl trinitrate, or the vasodilator prostaglandin, prostacyclin. In further studies, endothelin-l was co-infused with an inhibitor of nitric oxide production, NG-monomethyl-L-arginine, or after oral administration of the irreversible inhibitor of prostaglandin production, acetylsalicylic acid (aspirin). 3. At a low dose (5 pmol/min), endothelin-1 alone caused slowly developing and long-lasting venoconstriction (maximal constriction: 66 ± 4%). Although glyceryl trinitrate partially prevented endothelin-1-induced venoconstriction (maximum: 33 ± 5%), inhibition of nitric oxide production did not affect endothelin-1-induced venoconstriction (maximum: 55 ± 4%). 4. Prostacyclin was more effective at blocking the venoconstriction in response to endothelin-1 than glyceryl trinitrate (maximum: 12 ± 3%), and there was substantial potentiation of endothelin-1-induced venoconstriction after pretreatment with aspirin (maximum: 90 ± 3%). 5. Despite the capacity of nitric oxide to attenuate responses to endothelin-1, NG-monomethyl-L-arginine did not potentiate endothelin-1-induced venoconstriction, suggesting little or no stimulated production of nitric oxide in human veins. However, the potentiation of responses to endothelin-1 by aspirin indicates that endothelial production of prostacyclin attenuates responses to endothelin-1 in human veins in vivo.

Effect of in vivo nitrate tolerance on hypersensitivity to NO donors after NO-synthase blockade

2002 ◽  
Vol 80 (11) ◽  
pp. 1106-1118 ◽  
Author(s):  
Jodan D Ratz ◽  
Michael A Adams ◽  
Brian M Bennett
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Nitrate Tolerance ◽  
Metabolite Formation ◽  
No Donor ◽  
No Donors ◽  
Nos Inhibitors ◽  
Pressure Lowering ◽  
Oxide Synthase

Animals treated with nitric oxide synthase (NOS) inhibitors exhibit marked hypersensitivity to the blood pressure lowering effects of exogenous nitric oxide (NO) donors. We used this model as a sensitive index to evaluate the relative importance of reduced biotransformation of glyceryl trinitrate (GTN) to NO in the development of nitrate tolerance. NOS-blockade hypertension using NG-nitro-L-arginine methyl ester (L-NAME) caused a marked enhancement of the mean arterial pressure (MAP) decrease mediated by GTN in nontolerant rats. However, even large doses of GTN were unable to change the MAP in GTN-tolerant, NOS-blockade hypertensive animals. In contrast, the MAP responses to the spontaneous NO donor sodium nitroprusside (SNP) were completely unaltered in either tolerant rats or tolerant NOS-blockade hypertensive animals, indicating that NO-dependent vasodilatory mechanisms remain intact despite the development of GTN tolerance. The MAP-lowering effects of GTN in NOS-blockade hypertensive animals were restored 48 h after cessation of chronic GTN exposure. These alterations in the pharmacodynamic response to GTN during tolerance development and reversal were associated with parallel changes in the pattern of GTN metabolite formation, suggesting that the activity of one or more enzymes involved in nitrate metabolism was altered as a consequence of chronic GTN exposure. These findings suggest that the vasodilation resulting from the vascular biotransformation of GTN to NO (or a closely related species) is severely compromised in nitrate-tolerant animals, and that although other mechanisms may contribute to the vascular changes observed following the development of GTN tolerance, decreased GTN bioactivation is likely the most important.Key words: biotransformation, glyceryl trinitrate, hypertension, nitric oxide, tolerance.

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