Specific Inhibition of Acid Proteases from Brain, Kidney, Skeletal Muscle, and Insectivorous Plants by Diazoacetyl-DL-norleucine Methyl Ester and by Pepstatin*

1974 ◽  
Keyword(s):  
Skeletal Muscle ◽  
Methyl Ester ◽  
Specific Inhibition ◽  
Insectivorous Plants

Timing of Administration of Dexamethasone or the Nitric Oxide Synthase Inhibitor, Nitro-l-Arginine Methyl Ester, is Critical for Effective Treatment of Ischaemia-Reperfusion Injury to Rat Skeletal Muscle

1997 ◽  
Vol 93 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Baimeng Zhang ◽  
Kenneth R. Knight ◽  
Bruce Dowsing ◽  
Elizabeth Guida ◽  
Long H. Phan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Inducible Nos

1. The effects of the nitric oxide synthase (NOS) inhibitors, NG-nitro-l-arginine-methyl ester (l-NAME), nitroiminoethyl-l-ornithine and S-methylisothiourea on skeletal muscle survival following 2 h of tourniquet ischaemia and 24 h of reperfusion were compared with those of the antiinflammatory steroid, dexamethasone. 2. Administration of each of the NOS inhibitors or dexamethasone 30 min before reperfusion reduced the degree of skeletal muscle necrosis 24 h after reperfusion. 3. The influence of timing of drug administration was investigated. l-NAME administered 30 min before reperfusion, at 3 h after reperfusion, but not thereafter, significantly improved muscle survival compared with saline-treated controls. Dexamethasone administered 30 min before, or at 3 or 8 h after reperfusion, but not at 16 h, significantly improved muscle survival, but neither agent had protective effects when administered before ischaemia. 4. After 8 h of reperfusion of ischaemic skeletal muscle, cell-free homogenates contained Ca2+-independent (inducible) NOS activity which was reduced in dexamethasone-treated (2.5 mg/kg) rats. Furthermore, inducible NOS mRNA levels, as detected by reverse transcriptase-PCR, were increased after 8 h of reperfusion in saline, but not in dexamethasone-treated rats. 5. These data suggest a significant deleterious effect of endogenous NO which may be restricted to the first 3 h of the reperfusion phase of ischaemia-reperfusion injury, and raise the possibility of effective treatment of incipient reperfusion injury, even after several hours of reperfusion.

Specific inhibition of cardiac and skeletal muscle sarcoplasmic reticulum Ca2+ pumps by H-89

1997 ◽  
Vol 54 (9) ◽  
pp. 991-998 ◽  
Author(s):  
Philippe Lahouratate ◽  
Jacqueline Guibert ◽  
Jean-Claude Camelin ◽  
Isabelle Bertrand
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Specific Inhibition

scholarly journals Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide

2003 ◽  
Vol 94 (3) ◽  
pp. 935-940 ◽  
Author(s):  
John B. Buckwalter ◽  
Valerie C. Curtis ◽  
Zoran Valic ◽  
Stephen B. Ruble ◽  
Philip S. Clifford
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Methyl Ester ◽  
Vascular Remodeling ◽  
Treated Group ◽  
No Synthase ◽  
No Production ◽  
Ischemic Limb ◽  
Time Flow

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution ( N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly ( P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially ( P < 0.05) shorter in thel-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.

Ischemic tolerance in skeletal muscle: role of nitric oxide

1998 ◽  
Vol 275 (1) ◽  
pp. H94-H99 ◽  
Author(s):  
S. Pudupakkam ◽  
K. A. Harris ◽  
W. G. Jamieson ◽  
G. DeRose ◽  
J. A. Scott ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Methyl Ester ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Event ◽  
Reperfusion Period ◽  
Male Wistar Rats ◽  
Edl Muscle

We tested the hypothesis that ischemic preconditioning (PC) of skeletal muscle provided tolerance to a subsequent ischemic event 24 h later, and that such protection was due to nitric oxide (NO). Male Wistar rats, anesthetized with halothane, were randomly assigned to groups: ischemic (no PC; n = 11), PC ( n = 11), PC + N-nitro-l-arginine methyl ester (l-NAME; 100 μmol/l; n = 5), PC + N-nitro-d-arginine methyl ester (100 μmol/l; n= 4), PC + aminoguanidine (AMG; 100 μmol/l; n = 4), ischemic +l-NAME ( n= 4), or ischemic + AMG ( n = 4). PC consisted of 5× 10 min of ischemia and reperfusion, and, 24 h later, 2 h of ischemia were induced by a tourniquet applied to the limb. With the use of intravital microscopy, the number of perfused capillaries ( N pc) in the extensor digitorum longus (EDL) muscle was measured over a 90-min reperfusion period. The ratio of ethidium bromide- to bisbenzimide-labeled nuclei was used to estimate tissue injury. PC preserved N pc(23.6 ± 2.5) following 2 h of ischemia compared with sham muscles (11.5 ± 5.1), significantly elevating inducible NO synthase (iNOS) activity (81% increase), but did not afford protection to the parenchyma.l-NAME and AMG prevented ischemia-reperfusion-induced reduction in N pc in muscles without PC. However, after 90 min of reperfusion,l-NAME ( N pc = 15.0 ± 1.7), but not AMG ( N pc = 22.8 ± 3.1), significantly reduced the microvascular protection afforded by PC. We conclude that PC of the EDL muscle resulted, 24 h later, in protection to microvascular perfusion only, and that such protection was due to NO from sources other than iNOS.

Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α

2000 ◽  
Vol 279 (6) ◽  
pp. R2156-R2163 ◽  
Author(s):  
Giuseppe Alloatti ◽  
Claudia Penna ◽  
Filippo Mariano ◽  
Giovanni Camussi
Keyword(s):  
Skeletal Muscle ◽  
Methyl Ester ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
No Production ◽  
Force Frequency ◽  
Muscle Contractility ◽  
Tnf Α ◽  
Frequency Relationship

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-α (TNF-α) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-α (5–10 ng/ml) reduced contractility at every stimulation frequency (1–200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-α was suggested by the protective effect of N G-nitro-l-arginine methyl ester (l-NAME; 1 mM), but not of N G-nitro-d-arginine methyl ester (d-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 μM). TNF-α increased the production of PAF and NO. Similar to TNF-α, both S-nitroso- N-acetylpenicillamine (0.5–1 μM), an NO-generating compound, and PAF (10–20 nM) reduced EDL contractility. l-NAME, but not d-NAME, blocked the negative effect of PAF. Blockade of phospholipase A2, which is required for PAF synthesis, significantly reduced the effects of TNF-α. WEB-2170 inhibited NO synthesis induced by TNF-α and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-α and that NO production is downstream to the synthesis of PAF.

Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise

2000 ◽  
Vol 88 (4) ◽  
pp. 1192-1198 ◽  
Author(s):  
Timothy P. Gavin ◽  
David A. Spector ◽  
Harrieth Wagner ◽  
Ellen C. Breen ◽  
Peter D. Wagner
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Methyl Ester ◽  
Acute Exercise ◽  
Transforming Growth Factor ◽  
No Production ◽  
Vegf Mrna ◽  
Exercise Induced ◽  
Response To Exercise

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-β1 (TGF-β1) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF-β1 gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups ( n = 6 each): 1) saline + rest, 2) saline + exercise, 3) 30 mg/kg N ω-nitro-l-arginine methyl ester (l-NAME, a known NOS inhibitor) + rest, 4) 30 mg/kgl-NAME + exercise, 5) 300 mg/kg l-NAME + rest, 6) 300 mg/kg l-NAME + exercise, 7) 300 mg/kg N ω-nitro-d-arginine methyl ester (d-NAME, inactive enantiomer of l-NAME) + rest, and 8) 300 mg/kg d-NAME + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10° incline. VEGF, TGF-β1, and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF-β1 mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated ∼50% by 30 and 300 mg/kgl-NAME; the TGF-β1 mRNA increase was unaffected by 300 mg/kg l-NAME. In addition, 300 mg/kgd-NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg l-NAME had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life.

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