AIMIn order to elucidate the underlying mechanism of depressed maximal isometric twitch tension normalized by cross sectional area of muscle strip in unloaded soleus.

METHODSThe soleus and extensor digitorum longus (EDL) muscle strips were perfused in vitro and treated by 2,3-Butanedione monoxime (BDM).

RESULTSThe BDM decreased Pt of soleus and EDL in a concentration-dependent manner. The Pt could restored completely to normal level after washing out BDM. The isometric twitch duration was not altered during 1 mmol/L BDM of perfusion, but was shortened at 10 mmol/L dose. The time from maximal to half Pt in EDL was shorter than that in soleus during 10 mmol/L BDM of perfusion. The inhibitory effects of BDM on myosin ATPase activity were higher in EDL than in soleus. The inhibitory extent of BDM on myosin ATPase activity of soleus and EDL was lower than that on Pt.

CONCLUSIONThese results suggest that reduction in cross-bridge function of skeletal muscle may be one of reasons induced a decrease in its Pt. BDM is not a specific inhibitor on myosin ATPase activity and can affect multiple parts of excitation-contraction coupling in skeletal muscle.

Animals ; Diacetyl ; analogs & derivatives ; pharmacology ; Isometric Contraction ; drug effects ; physiology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle, Skeletal ; drug effects ; physiology ; Myosins ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the contraction effect of endothelin-1 (ET-1) on human hepatic stellate cells (HSCs) and the inhibition of salianic-acid B (SA-B) on ET-1, to explore the acting link and the possible mechanism.

METHODSHSC were isolated from human normal liver tissue by enzyme digestion and Nycondenz density gradient centrifugation. The contraction of ET-1 on passage HSCs and the intervention of SA-B with three doses (low-, middle-, and high-) on the contraction were observed by collagen gel contraction. ET-1 and SA-B were directly added to the serum-free medium of HSCs, then calcium ion concentration was detected by laser scanning confocal microscope.

RESULTSCollagen gel contraction experiments showed that ET-1 could induce the contraction of HSC directly (P < 0.01). Three doses of SA-B significantly inhibited the contraction effects of ET-1 on HSCs (all P < 0.01). After adding the ET-1, HSCs morphology changed obviously with the number of cells decreased. However, SA-B inhibited the changes. Laser scanning confocal microscope experiments revealed that ET-1 stimulated the transiently rapid increase of intracellular calcium ion concentration, and the effects was obviously inhibited when SA-B was added.

CONCLUSIONSSA-B could inhibit the contraction of HSCs induced by ET-1, and its mechanism might be related to the lowing of free calcium ion concentration in HSCs. This anti-contraction effect of SA-B is perhaps one of the mechanisms of its anti-fibrosis and anti-portal hypertension effects.

Benzofurans ; pharmacology ; Cells, Cultured ; Endothelin-1 ; antagonists & inhibitors ; Hepatic Stellate Cells ; cytology ; Humans ; Isometric Contraction ; drug effects

OBJECTIVETo investigate the effect of ascorbic acid (VC) on relaxation of ex vivo Bufo gastrocnemius during sustained isometric contraction.

METHODSDynamic tension of the muscle was recorded under constant voltage stimulation within 7.0 min at 2 s intervals. The rest tension and relaxation rate of the muscle was obtained by weighted fitting to the relaxation process of tension <90% of its peak with a mono-exponential model to characterize the muscular relaxation.

RESULTSVC at 2.0 mmol/L alone or in combination with the inhibitors of the antixoidation enzymes (surperoxide dismutase, glutathione peroxidase and catalase) resulted in negligible alterations in the muscular relaxation kinetics. VC combined with the inhibitor of surperoxide dismutase resulted in significantly lowered relaxation rate while increased rest tension, but VC with the inhibitor of either catalase or glutathione peroxidase showed negligible action. VC combined with the inhibitors of all the 3 enzymes also caused significant effect on the muscular relaxation kinetics, which was similar the effect of VC with superoxide dismutase inhibitor.

CONCLUSIONVC at high concentration may result in oxidative toxicity to the biological system rich in transitional metal ion complexes but with low antioxidation capacity by causing superoxide-mediated oxidative damages.

Animals ; Ascorbic Acid ; pharmacology ; Bufonidae ; Electric Stimulation ; In Vitro Techniques ; Isometric Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Muscle, Skeletal ; drug effects ; physiology

This study was designed to determine the effects of ketamine on contractions induced by norepinephrine (NE), K+ or histamine (Hist) and on agonist-induced calcium mobilization, in rabbit thoracic aorta with or without endothelium. Contractile responses to NE, K+ or Hist were markedly attenuated by prior exposure to ketamine. Subsequent addition of ketamine to the rabbit aorta undergoing an isometric contraction induced by NE, K+ or Hist also decreased the contractile responses in a calcium ion concentration-dependent manner. Preincubation with ketamine produced a concentration-dependent inhibition of contractile responses elicited by the addition of calcium ion (1.6 mM) to a Ca(++)-free depolarizing solution. However, the phasic contraction produced by NE with 2mM lanthanum pretreatment, which is release of intracellular calcium, was also inhibited by ketamine. Moreover, the tonic contraction produced by NE after depletion of the agonist-releasable pool of intracellular calcium, which is thought to be due to calcium influx, was depressed by ketamine. These data suggest that ketamine relaxes NE-contracted rings of rabbit thoracic aorta by decreasing calcium entry and by producing an extracellular calcium-independent relaxant effect.
Animal ; Aorta, Thoracic ; Calcium/pharmacology ; Dose-Response Relationship, Drug ; Female ; Histamine/pharmacology ; Isometric Contraction/drug effects ; Ketamine/*pharmacology ; Male ; Muscle Contraction/*drug effects ; Muscle, Smooth, Vascular/*drug effects ; Norepinephrine/pharmacology ; Rabbits ; Support, Non-U.S. Gov't

We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.
Acetylcholine/pharmacology ; Anemia/metabolism ; Anemia/etiology ; Anemia/drug therapy* ; Animal ; Aorta, Thoracic/physiology ; Body Weight ; Erythropoietin/pharmacology* ; Hypertension, Renal/metabolism ; Hypertension, Renal/drug therapy ; Isometric Contraction/drug effects ; Kidney/enzymology ; Kidney Failure, Chronic/metabolism* ; Kidney Failure, Chronic/complications ; Male ; Nitrates/urine ; Nitrates/blood ; Nitric Oxide/metabolism* ; Nitric-Oxide Synthase/metabolism ; Nitrites/urine ; Nitrites/blood ; Nitroprusside/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology ; Vasodilator Agents/pharmacology