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PubMed2001

Effects of volatile anesthetics on ryanodine-treated ferret cardiac muscle.

The volatile anesthetics halothane, isoflurane, and sevoflurane depress myocardial contractility by decreasing transsarcolemmal Ca2+ influx, Ca2+ release from the sarcoplasmic reticulum, Ca2+ sensitivity of the contractile proteins, and cross-bridge performance. The aim of this study is to assess and compare the effects of halothane, isoflurane, and sevoflurane on contractility in conditions in which sarcoplasmic reticulum Ca2+ release is abolished by pretreatment with ryanodine. Ferret right ventricular papillary muscles were exposed to ryanodine at 10(-6) M and then to incremental concentrations of halothane, isoflurane, or sevoflurane. In the presence of ryanodine, each anesthetic decreased isometric and isotonic contractility in a reversible, concentration-dependent manner with no differences between anesthetics and with little or no effect on time variables. It is likely that differences between anesthetic effects on contraction amplitude in isometric and isotonic twitches reside in their effects on the sarcoplasmic reticulum.

Anesthetics, Inhalation↗
PubMed1992

Effects of vasoconstrictors on isolated rabbit coronary arteries exposed to isotonic iohexol. Potassium chloride-, histamine-, endothelin-, and prostaglandin-F2 alpha-induced contractions on arteries exposed to iohexol without and with osmotic additions (sodium chloride or glucose).

RATIONALE AND OBJECTIVES: A major effect of contrast media (CM) on coronary vessels is vasodilatation, but occasionally, both ionic and nonionic media may cause coronary artery spasm. The influence of CM on the actions of vasoactive substances is not well known. To investigate the effects on rabbit coronary arteries of an iso-osmolar nonionic CM, iohexol (140 mg I/mL) the vasoconstrictors potassium chloride (KCl), histamine, endothelin, and prostaglandin-F2 alpha (PGF2 alpha) were used. The effects of iohexol with 30 to 150 mM sodium chloride (NaCl) or with 25-50 g/L glucose also were investigated. METHODS: Coronary artery segments were mounted between two L-shaped prongs in tissue baths with buffer solution. Before each investigation, buffer was exchanged with iohexol solution. Increasing concentrations of a vasoconstrictor were added, and the constriction of the vessels was recorded. RESULTS: Iohexol caused a comparatively small inhibition of the contractile effects of histamine and endothelin. This meant little reduction in maximal contraction (Emax), and the concentration of constrictory substance resulting in half maximal contraction (EC50) compared with buffer solution. Iohexol also caused a small reduction in Emax of KCl, but EC50 was significantly lower. Adding NaCl or glucose to iohexol decreased Emax and increased EC50. Iohexol inhibited most of the contractile effect of PGF2 alpha, but adding NaCl increased Emax slightly. CONCLUSIONS: The effects caused by a nonionic CM on coronary arteries cannot be attributed to osmolality alone. The CM influenced the effects of vasoconstrictors to differing degrees, but the inhibition of the CM per se was usually small.

Animals↗
PubMedDate not supplied

Cerebral arterial smooth muscle contraction by thromboxane A2.

The contractile effects of thromboxane A2 (TxA2), a labile arachidonic acid metabolite, were studied in arterial smooth muscle strips. TxA2 was generated upon the addition of 255 nM prostaglandin cyclic endoperoxide H2 to human platelet particles in the muscle bath. Using the isometric contaction produced by 40 mM K+ in isotonic saline as the reference contraction, bovine middle cerebral artery strips contracted to 153 +/- 14% of the reference response while bovine coronary and porcine coronary, renal and common carotid strips contracted to 47 +/- 3, 26 +/- 5, 43 +/- 2 and 2 +/- 1% of reference, respectively. The cerebral artery response to the TxA2 generating system was as great as the maximum response to prostaglandin F2alpha and two times the maximum response to 5-hydroxytryptamine. Because TxA2 is formed by brain tissue and released from aggregating platelets, it may be important in the pathogenesis of spasm associated with injured brain tissue or pathologic changes leading to platelet aggregation.

Animals↗
PubMed1992

The time course of thyroid-hormone-induced changes in the isotonic and isometric properties of rat soleus muscle.

Rat thyroidectomy resulted in changes in a number of parameters used to characterise the mechanical and histochemical status of skeletal muscle. Thus thyroidectomy resulted in a prolongation of soleus slow-twitch muscle isometric contraction time and half-relaxation time with a reduced maximum velocity of shortening and maximum rate of development of tetanic tension but no significant change in twitch: tetanus ratio i.e. the ratio of twitch force/unit area to tetanic force/unit area. In addition the percentage of IIA fibres was reduced and the percentage of type I fibres increased. Triiodothyronine, administered to hypothyroid rats, brought about a speeding of these parameters again with no change in twitch: tetanus ratio. There was an increase in the percentage of IIA fibres with a concomitant reduction in the percentage of type I fibres. These changes were induced over 18 days and resulted in isotonic and isometric properties almost identical to those of soleus muscles from chronically hyperthyroid rats; speeding could be detected as early as 2 days after triiodothyronine had been given. Consideration is given to the possibility that changes in myosin isoforms and/or the kinetics of changes in intracellular calcium concentration in activation and relaxation could account for the time course of the observed changes.

Animals↗
PubMed1989

Effects of intracellular ruthenium red on excitation-contraction coupling in intact frog skeletal muscle fibres.

1. Ruthenium Red (RR) blocks sarcoplasmic reticulum (SR) Ca2+ release in disrupted muscle preparations and this block has been used as a marker for the physiological Ca2+ release pathway. To investigate whether RR can also affect SR Ca2+ release in living muscle, optical signals reflecting Ca2+ release have been measured in intact single frog twitch fibres microinjected with RR. 2. The total myoplasmic concentration of RR, [RRT], was obtained from measurements of RR-related absorbance and apparent diffusion constant, Dapp, of RR in myoplasm was estimated. The value of Dapp was about 1/30 of that expected and can be explained if the majority of RR (approximately 97%) was bound in myoplasm and free [RR] was only 1/30 of [RRT]. 3. Sarcoplasmic reticulum Ca2+ release following action potential stimulation was assessed from a Ca2+-related change in intrinsic birefringence. The birefringence signal was blocked in the presence of RR and the degree of block was clearly dependent upon [RRT]. At 16 degrees C the estimated [RRT] for half-block of the birefringence signal was 23 +/- 4 microM (+/- S.E. of mean; n = 3), and for half-block of the Ca2+ release process itself was 72 +/- 14 microM. The estimated free [RR] for half-block is then 0.8 +/- 0.1 and 2.4 +/- 0.5 microM, respectively. In the cold (6-8 degrees C), the half-blocking concentration of RR, referred to [RRT], appeared to be about 3-fold smaller than that observed at 16 degrees C. 4. The values estimated for the free [RR] which caused half-block of Ca2+ release in intact muscle fibres are in the range reported for RR's action in disrupted preparations, thus supporting the conclusion that the RR-blockable channel observed in disrupted muscle is the physiologically important Ca2+ release channel. 5. Intramembrane charge movements in skeletal muscle are thought to underlie the dependence of SR Ca2+ release on transverse tubular membrane potential. Charge movements were measured in RR-injected fibres at 4-6 degrees C using a three-microelectrode, middle-of-the-fibre voltage-clamp technique. Injected fibres did not survive well in solutions made hypertonic to prevent fibre movement and allow measurement of suprathreshold charge; therefore charge movements below contraction threshold were studied in isotonic solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Low potency of Ca antagonists in smooth muscle from different levels of the respiratory tract.

Respiratory smooth muscle at different levels of the respiratory tract was isolated from rabbit, rat and guinea-pig and incubated with the Ca antagonists, verapamil, D-600, felodipine, and nifedipine. There was no effect of the Ca antagonists when added on top of an already developed contraction. When added before the contractile agent at high concentrations (10-100 microM) the Ca antagonists reduced the contractions. Lanthanum (2 mM) was considerably more effective to prevent contractions than the Ca antagonists. Preparations from the trachea and bronchus responded in all animals, whereas the third generation bronchus from rat and guinea-pig failed to contract and that from rabbit showed very weak contractions. The failure to contract was not specific for the agonist, as depolarization with isotonic potassium solution (124 mM) did not evoke contractions either. Microscopic investigation showed well-developed smooth muscle in the trachea and main bronchus of the rat, whereas the muscle of the third generation bronchus was inhomogenous with scattered groups of muscle cells.

Animals↗
PubMed1993

Maximum shortening speed of motor units of various types in cat lumbrical muscles.

1. Isotonic shortening of cat superficial lumbrical muscles was studied during maximal tetanic contractions of single motor units of identified types. For each motor unit, the maximal speed of contraction, Vmax, was determined by extrapolating to zero the hyperbolic relation between applied tension and speed of shortening. 2. The maximal speeds of shortening of motor units formed a continuum with the highest velocities observed for the fast fatigable motor units and the lowest for the slow motor units. 3. On average, the maximum speed of shortening increased with the tetanic tension developed by the motor units. 4. In motor units with isometric twitch contraction times less than 35 ms, these times showed a significant inverse correlation with Vmax. Progressively longer contraction times were associated with rather small changes in Vmax. 5. The implications of these findings on the speed of muscle shortening during motor-unit recruitment are discussed.

Animals↗
PubMed2005

Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes.

AIMS: To study the effects of progesterone on contractile activity of smooth muscle strips and on ion currents and intracellular Ca2+ ([Ca2+]i) intensity in single colonic myocytes in guinea pig proximal colons. METHODS: Strips and single cells were dissected from female guinea pig proximal colon. Contraction of strips through an isotonic transducer was assessed and the responsible currents to progesterone were recorded with EPC-9 amplifier in nystatin perforated whole-cell configuration. Detection of [Ca2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. RESULTS: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 microM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (K(Ca)) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% +/- 13% (n = 9, p < 0.01), and to 143% +/- 12% (n = 8, p < 0.01) when perfused with 10 mcM onapristone. Progesterone reduced L-Ca2+ currents to 67% +/- 6% (n = 7, p < 0.01) and had no effect with 5 microM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% +/- 12% (n = 8, p < 0.01). CONCLUSION: Progesterone decreases the contraction of colonic smooth muscles by enhancing K(Ca) currents and reducing Ca2+ influx.

Animals↗
PubMed1967

The significance of adenosine cyclic 3',5'-monophosphate for the contraction of smooth muscle.

1. The influence of adenosine cyclic 3',5'-monophosphate (3',5'-AMP) and of drugs believed to increase or decrease its concentration in the tissues has been determined on the response of vascular and uterine smooth muscles to catecholamines. Generally, drugs believed to increase tissue content of 3',5'-AMP potentiated the responses and those believed to decrease it depressed them.2. The cardiovascular responses of dogs (with major vessels occluded in the chest) to carotid occlusion were potentiated by infusions of theophylline and sodium fluoride. Infusion of theophylline also potentiated the response of the occluded abdominal vessels to noradrenaline.3. Intravenous infusions of theophylline and sodium fluoride potentiated pressor responses to catecholamines in the pithed rat. Infusions of iminazole depressed the responses in two animals and was without effect in two others.4. In spinal cats intravenous infusions of theophylline potentiated pressor responses to catecholamines, but sodium fluoride was without effect.5. Contractions of the isolated rat aortic strip to noradrenaline were always potentiated by sodium fluoride and by theophylline, and depressed by iminazole, when they were recorded isometrically. Theophylline always potentiated the contractions, when they were recorded isotonically but sodium fluoride was mostly, and iminazole always, ineffective.6. 3',5'-AMP in concentrations from 0.1 to 20 mug/ml. potentiated the responses of the isolated rat aortic strip to noradrenaline in thirty-eight experiments out of hundred. Concentrations from 10 to 500 mug/ml. sometimes depressed contractions recorded isometrically. In five experiments, exposure to low concentrations for 3 hr increased the resting tension of the preparation.7. Responses to noradrenaline of uteri from oestradiol-treated rabbits were potentiated by vasopressin and by sodium fluoride, but not by theophylline or iminazole. In progesterone-treated animals the responses were unaffected by vasopressin and sodium fluoride, but potentiated by theophylline and depressed by iminazole. 3',5'-AMP was without effect on the uterine responses.8. It is concluded that the results support the view that an increase in the tissue content of 3',5'-AMP potentiates the contraction of vascular and uterine smooth muscle in response to catecholamine. This view is supported by the observation that the nucleotide itself can potentiate the responses of the rat aortic strip to noradrenaline.

Adenine Nucleotides↗
PubMed1997

Characterization of the contraction to 5-HT in the canine colon longitudinal muscle.

1. Although conscious dogs have often been used for colonic motility studies with 5-hydroxytryptamine (5-HT), the effects of 5-HT on the isolated colon have not been thoroughly characterized yet. The current study was undertaken to characterize the response to 5-HT of the canine isolated colon longitudinal muscle. 2. Longitudinal strips of canine midcolon deprived of (sub)mucosa were prepared for isotonic measurement. 5-HT induced contractions from 3 nM onwards, which were not affected by selective inhibition of 5-HT re-uptake, monoamine oxidase or blockade of alpha-adrenoceptors. Tetrodotoxin (0.3 microM) did not affect the responses to 5-HT, suggesting that smooth muscle 5-HT receptors are involved. The selective 5-HT4 receptor antagonist SB 204070 (10 nM) slightly enhanced contractions to 5-HT and therefore it was included in the organ bath solution in all further experiments. The 5-HT1 and 5-HT2 receptor antagonist methysergide (0.1 microM) depressed the curve to 5-HT, but the selective 5-HT3 receptor antagonist granisetron (0.3 microM) had no effect. 3. Besides 5-HT, alpha-methyl-5-HT (alpha-Me-5-HT), 5-methoxytryptamine (5-MeOT), 2-methyl-5-HT (2-Me-5-HT) and 5-carboxamidotryptamine (5-CT) also induced contractions, with the following rank order of potency (pEC50 values in parentheses): 5-HT (6.9) = alpha-methyl-5-HT (6.9) > 2-Me-5-HT (5.8) = 5-MeOT (5.7) = 5-CT (5.6), indicative of 5-HT2 receptor involvement, alpha-Me-5-HT produced a bell-shaped curve, which was not affected by alpha-adrenoceptor blockade. 5-HT, 5-MeOT, 2-Me-5-HT and 5-CT produced a monophasic concentration-response curve, consistent with an interaction with a single receptor site. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and tryptamine only induced contractions at a concentration exceeding 1 microM. 4. The selective 5-HT2B receptor antagonist SB 204741 (0.3 microM) did not affect the curve to 5-HT. Ketanserin, cisapride and spiroxatrine behaved as competitive antagonists with pKb values of, respectively, 8.4, 8.1 and 6.7. Spiroxatrine (1 microM) shifted the curve to 5-MeOT rightward yielding an apparent pA2 of 7.1. Other antagonists at 5-HT2A receptors also surmountably inhibited the contractions to 5-HT (apparent pA2 value in parentheses): mesulergine (8.2), cinanserin (8.2), yohimbine (6.2) and mianserin (8.6). However, as well as a rightward shift, methiothepin (8.3), pizotifen (8.6) and spiperone (8.8) also caused a depression of the curve, indicative of "pseudo-irreversible' antagonism. Taken together, the above mentioned affinity estimates most closely corresponded to literature affinity values for 5-HT2A receptors. 5. It was concluded that 5-HT induces contractions of the canine midcolon longitudinal muscle primarily by stimulation of smooth muscle 5-HT2A receptors. The presence of inhibitory 5-HT4 receptors cannot be ruled out.

Animals↗
PubMed1977

Mechanical properties of taenia coli smooth muscle in spontaneous contraction.

The following mechanical tests have been performed on spontaneously contracting taenia coli: isometric step stretch, isotonic step loading, and length-tension. Passive stress-strain tests have also been done. Information on spontaneous contraction was more readily obtained in isometric tests. In length-tension tests, each isometric contraction was analyzed on a phase plane which is a representation of muscle stress, sigma(t), versus the rate of change of stress, sigma(t). The curve in the phase plane provided parameters for describing spontaneous contraction as a function of muscle length, L. The maximum active stress in a cycle of spontaneous contraction, S(L)max, and the maximum rate of increasing active stress, [S(L)]max, were shown to depend on L in the same way. Both parameters attain a maximum value (upper bound) at the same muscle length, Lmax. When L less than Lmax, the minimum stress in a spontaneous contraction, sigma(l)min, is negligible. If L greater than Lmax, sigma(L)min increases nonlinearly and is equal to the passive stress, tau(L), in an epinephrine-relaxed muscle. The results show that the ratio of [S(L)]max to S(L)max, eta(L), is constant for a physiological range of muscle length. This suggests that eta(L) may be used as an index of contractility for taenia coli.

Animals↗
PubMed1994

[The level of cyclic nucleotides during spontaneous smooth-muscle contractions in the guinea pig].

The relationships between isotonic tension and changes in cAMP and cGMP levels was studied in isolated preparations of the guinea-pig taenia coli and myometrium during spontaneous contractions. No significant changes in cyclic nucleotide levels were detected at any stage of the spontaneous contraction-relaxation cycle. The finding suggests that these changes play no significant role in the regulation of spontaneous contractions of the taenia coli and myometrium. However, other data obtained suggests the possibility of combined actions of the cGMP and phosphatidylinositols in control of smooth muscle motility during muscarine stimulation.

Animals↗
PubMed1985

Continuum rheology of muscle contraction and its application to cardiac contractility.

A set of constitutive equations is proposed to describe the mechanics of contraction of skeletal and heart muscle. Fiber tension is assumed to depend on the degree of chemical activation, the stretch ratio, and the rate of stretching of the fibers. The time rate of change of activation is governed by a differential equation. The proposed constitutive equations are used to model the time courses of isotonic and isometric twitches during contraction and relaxation phases of the muscle response to stimulation. Various contractility indices of the left ventricle are considered next by using the proposed constitutive equations. The present analysis introduces a new interpretation of the index of contractility (dP/dt)/P used in cardiac literature. It is shown that this index may not be related at all to the maximum speed of shortening and that it may be dependent on both preload and afterload. The development of pressure during isovolumetric contraction of the left ventricle is shown to be governed by a differential equation describing the time rate of change of tension during isometric contraction of myocardium fibers.

Animals↗
PubMed1984

[Cationic regulation of myocardial contraction and relaxation when contraction frequency is increased].

During augmentation of frequency of contractions or Ca2+ perfusate concentration the velocity of isotonic relaxation increased much more than the velocity or amplitude of contraction. The phenomenon of predominant activation of relaxation ( PPAR ) was less prominent at decreased Ca2+ concentration acidosis (pH 6,85), under action of calmodulin inhibitor, trifluoperazine, or replacement of Ca2+ ions by Sr2+. Diminution of Na2+ concentration to 25 mM was followed by apparent signs of cellular Ca2+--overload and elimination of PPAR . The results coincide with the suggestion that PPAR is caused by activation of calmodulin-dependent Ca2+ removal from the myoplasma and myofibrils.

Animals↗
PubMedDate not supplied

Antagonism produced by hypertonic nutrient solutions on the depressive effect of carbofuran on isolated guinea pig atria.

The action of hyperosmotic nutrient solutions on the depressive effects of carbofuran was studied on spontaneously contracting guinea pig atria. The force and frequency of contraction were recorded using an isotonic lever. Carbofuran 33.0 micrograms ml-1 produced a gradual depressive effect. The time for stabilization of the depressive effect was 6.0 +/- 2.3 min. After the depressive effect of carbofuran was established, NaCl, mannitol, or urea were introduced into the organ bath to increase the osmolarity of the nutrient solution to about 100 mosmol kg-1 of water. This resulted in a reversal of the contraction force and frequency to the initial levels. The addition of the osmotic agents at the same concentrations before the addition of 33.0 micrograms ml-1 carbofuran avoided its depressive effect on guinea pig atria.

Animals↗
PubMed1988

Atrial natriuretic peptide secretion in response to volume expansion and contraction in normal man.

The plasma concentrations of ANP in response to isotonic saline-induced volume expansion and furosemide-induced volume contraction in 12 healthy men were measured by radioimmunoassay. The total ANP content was calculated by multiplying the circulating plasma volume (CPV) with the plasma ANP concentration, assuming that most of the ANP remained in the blood vessels. In addition, extracellular fluid volume (ECFV) was measured. After overnight dehydration, plasma ANP concentration significantly increased after isotonic saline was infused, but the urinary ANP concentration did not change essentially. After furosemide-induced volume concentration, plasma ANP concentrations significantly decreased, but the urinary ANP concentrations did not change essentially. As the CVP and ECFV changed, the total plasma ANP also changed. The correlation between these effects was highly significant (r = 0.84 and 0.67, N = 11, respectively). The chromatogram obtained from the plasma in the dehydrated state showed that the area of the high molecular weight ANP peak was relatively large compared with the total area of all ANP peaks. This area of the high molecular weight ANP peaks decreased after saline infusion. In the urine, only the alpha-ANP peak was noted and no high molecular weight ANP peak appeared in the chromatogram. These results indicate that amount and type of ANP secretion may change depending on circulating plasma volume.

Adult↗
PubMed1975

Voluntary skeletal muscles: a unifying theory on the relationship of their electrical and mechanical activities.

Experiments designed to examine the relationship between electrical and mechanical events in voluntarily contracting human muscle were performed. Experiments reported in the literature, as well as our own, were categorized according to technique into one of four types: (1) isometric-isotonic, (2) isometric-anisotonic,(3) anisometric-isotonic or (4) anisometric-anisotonic. A general relationship between the absolute value of the surface electromyogram (the absolute value of E and the force (F) generated by the contraction is proposed. This is the integral of the absolute value of E dt = k-1integralF dx i-2integralF dt, where k-1 and k-2 are constants. In the isometric-isotonic condition, this equation reduces to a linear relation between the average electromyogram and the force of contraction. A quadratic relation exists in the isometric-anisotonic, constantly increasing contraction, between the integrated electromyogram and the force of contraction. Also, this equation predicts linear relations for anisometric-isotonic contractions, and quadratic relations for an accelerated rate of contraction, between the average electromyogram and force of contraction. Both the data reported in the literature and our data provide confirmatory evidence for the unifying theory offered in this paper.

Adult↗
PubMed2002

Smooth muscle 5-HT2A receptors mediating contraction of porcine isolated proximal stomach strips.

1. The aim of this study was to characterize the 5-HT receptors involved in the 5-HT-induced contraction of longitudinal muscle (LM) strips of porcine proximal stomach. This was done in a classical organ bath set-up for isotonic measurement. 2. The concentration-contraction curve to 5-HT was not modified by 5-HT(3) and 5-HT(4) receptor antagonism. Methysergide, ketanserin and mesulergine antagonized the curve to 5-HT. Concomitantly, increasing concentrations of ketanserin and mesulergine progressively revealed a biphasic nature of the 5-HT curve. Ketanserin antagonized the low-affinity receptor while it did not modify the high-affinity receptor. 3. Tetrodotoxin did not influence the concentration-contraction curve to 5-HT neither in the absence nor presence of ketanserin, indicating that nerves are not involved. 4. Ketanserin competitively antagonized the monophasic concentration-response curve to alpha-Methyl-5-HT, yielding a Schild slope that was not significantly different from unity. After constraining the Schild slope to unity, a pK(B) estimate of 8.23+/-0.90 was obtained. This affinity estimate of ketanserin closely approximates previously reported affinities at 5-HT(2A) receptors. 5. In the presence of ketanserin (0.1 microM; exposing the high-affinity receptor), a wide range of 5-HT receptor antagonists covering all 5-HT receptors known, was tested. Only methysergide and ritanserin inhibited the response to 5-HT, thus expressing affinity for the high-affinity receptor. This did not reveal the identity of the receptor involved. 6 It can be concluded that 5-HT induces pig proximal stomach (LM) contraction via 5-HT(2A) receptors located on smooth muscle. A ketanserin-insensitive phase of contractions could not be characterized between the actually known classes of 5-HT receptors with the pharmacological tools that were used.

Animals↗