Contractility In Guinea Pigs Research Articles

Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms

The purpose of this study was to investigate the mechanisms involved in the excitatory effect induced by genistein in isolated guinea pig left ventricular papillary muscles and to determine relationship of genistein action with the tyrosine kinase pathway and phosphatidylinositol 3-kinase (PI3K) activity, the cyclic adenosine 5′-monophosphate (cAMP) signal system and the sarcoplasmic reticulum Ca 2+ mobilization. Genistein (1–100 μM) significantly increased contraction of left ventricular papillary muscles from male and female guinea pigs in a concentration-dependent manner and its action had no obvious gender differences. Prior treatment with an L-type Ca 2+ channel blocker verapamil hydrochloride, β-adrenoceptor inhibitors propranolol and atenolol, an inhibitor of Na +–Ca 2+ reverse exchanger Kb-r7943 or the blocker of estrogen receptor ICI 182,780 failed to alter the positive inotropic effect induced by genistein in papillary muscles. However, tyrosine phosphatase inhibitor, sodium orthovanadate or a potent phosphotyrosine phosphatase inhibitor bpV (phen) could partly but significantly reduce the stimulatory action of genistein. Interestingly, insulin-like growth factor-1, a known PI3K activator could also decrease the stimulatory action of genistein obviously, but the PI3K inhibitor LY294002 had no significant effect on the stimulatory action of genistein. The excitatory effect of genistein was markedly attenuated not only after treatment with an inhibitor of cAMP synthesis Sq 22536, carbachol or an inhibitor of specific protein kinase A H-89, but also after the inhibition of sarcoplasmic reticulum Ca 2+ mobilization by ruthenium red, ryanodine or the inhibitor of sarcoplasmic reticulum Ca 2+-ATPase thapsigargin. All these results indicate that the excitatory effects of genistein in papillary muscles are due to the inhibition of tyrosine kinase pathway and PI3K activity, thereby locally activating cAMP signal transduction and facilitating intracellular Ca 2+ mobilization, but are not related to the activation of β-adrenoceptor, the Na +–Ca 2+ reverse exchange and the estrogen receptor.

Effects of ceftriaxone sodium on in vitro gallbladder contractility in guinea pigs 1

It has been reported that ceftriaxone may induce the formation of gallstones. Changes of gallbladder motility may play a role in this phenomenon. The present study was designed to analyze the gallbladder contractility of ceftriaxone sodium-treated guinea pigs in response to different agonists. Twenty adult guinea pigs were randomly divided into two groups. Ten guinea pigs were treated with ceftriaxone sodium (100 mg/kg/day) for 10 days, whereas the remaining 10 served as the control group, receiving 1 ml of distilled water during 10 days as placebo. By the end of the experimental period the animals were sacrificed and the gallbladders were removed. The responses to KCl, papaverine, sodium nitroprusside, carbachol, and histamine on gallbladder strips from control and experimental groups were recorded and analyzed. There was no significant difference between the responsiveness to KCl, papaverine, and sodium nitroprusside on tissues isolated from experimental and control groups. Comparison of the two groups revealed that the maximum responses (E(max)) to carbachol and histamine were significantly reduced in the experimental group, without any change in the pD(2) values. These data indicate that, after ceftriaxone sodium therapy, the decreased maximum contractile response to carbachol and histamine may contribute to the formation of gallstones.

Effect of peritonitis on gallbladder smooth muscle contractility in guinea pigs

Background The mechanisms involved in the impaired gallbladder contractile response in peritonitis are unknown. The aim of this study was to determine the effect of peritonitis on the contraction and relaxation responses to different agonists in gallbladder smooth muscle in guinea pig. Materials and methods Peritonitis was induced by cecal ligation and puncture (CLP) in 10 guinea pigs. Another group of 10 guinea pigs underwent a sham operation and acted as controls. Twenty-four hours after the operation, the guinea pigs were killed, and gallbladder strips were placed in organ bath. The contraction responses to KCl, carbachol, and histamine, and relaxation responses to cyclooxygenase inhibitors (indomethacin, nimesulide, and DFU) on KCl-induced contractions were recorded. Results There was no significant difference between the contractile responsiveness to KCl, but maximum contractile responses ( E max) to carbachol and histamine were significantly reduced. Indomethacin, nimesulide, and DFU concentration dependently inhibited on KCl-induced contractions of gallbladder smooth muscle. E max values of indomethacin, nimesulide, and DFU were significantly reduced in the peritonitis group compared with controls ( P < 0.05). The inhibitor effects of nimesulide and DFU were considerably similar, but inhibitor effect of indomethacin was significantly less than that measured for nimesulide and DFU in both control and peritonitis groups ( P < 0.05). Conclusions The contraction responses to carbachol and histamine and relaxation responses to COX inhibitors on gallbladder smooth muscle are significantly decreased by peritonitis. Although the mechanism of the decrease in contraction and relaxation responses in CLP-induced peritonitis is completely unknown, we speculate that impaired smooth muscle responses may be related to an alteration in the regulation of receptor/postreceptor excitation-response coupling and/or through changes on Ca 2+ influx.

Species-dependent effects of increasing hypoxia on functions and energy balance in isolated atria

1. 1. The hypoxia-induced changes of contractile force, frequency and diastolic tension in isolated atria from guinea pig, rat and rabbit were studied together with tissue content of adenine nucleotides, creatine phosphate and lactic acid. 2. 2. Increasing hypoxia induced a progressive reduction of contractility in guinea pig, rat and rabbit atria. Hypoxia also induced a progressive reduction of frequency in rat atria, whereas atrial rate decreased significantly only during drastic hypoxia in guinea pig and rabbit. In spontaneously beating atria, hypoxia increased diastolic tension only in rat. 3. 3. After 30 min of drastic hypoxia, ATP decreased in guinea pig and rabbit but not in rat atria. Creatine phosphate decreased and lactic acid increased in all three species. 4. 4. These data suggest that: (a) hypoxia-induced changes in atrial function and in metabolic content are species-dependent; (b) hypoxia-induced inhibition of atrial activity could represent protection aimed at saving energy.

Nifedipine inhibits cholecystokinin-induced gallbladder contraction

Nifedipine is a calcium channel blocker which results in relaxation of smooth muscle. Although it has been utilized clinically to treat cardiovascular disease, and more recently spastic disorders of the esophagus and colon, its effects on gallbladder contractility have not been clearly defined. We tested the effects of nifedipine on gallbladder contraction stimulated by cholecystokinin (CCK) in a conscious guinea pig model and in healthy human volunteers. Gallbladder contraction was measured in response to repeated injections of CCK before and after intravenous nifedipine given to groups of five guinea pigs in a dose of 100, 200, or 300 μg. Nifedipine virtually abolished spontaneous interdigestive gallbladder contractile activity and decreased resting gallbladder tone. The mean amplitude of gallbladder contraction in response to CCK was decreased by 45, 73, and 67% ( P < 0.01), in response to the nifedipine doses of 100, 200, and 300 μg, respectively. The integrated gallbladder contractile response and the rate of rise of gallbladder pressure in response to CCK were also significantly decreased by nifedipine. In nine healthy human volunteers, gallbladder emptying was measured by radionuclide cholescintigraphy in response to CCK infusion; on another day the study was repeated after oral administration of 10 mg nifedipine. Ejection fraction was significantly decreased by nifedipine from 72 ± 5 to 51 ± 5% ( P < 0.001). These data demonstrate that nifedipine is a potent inhibitor of gallbladder contractility in guinea pigs and man. This may provide the basis for the use of nifedipine clinically in the treatment of biliary colic and also raises questions about the potential effect of longterm nifedipine use on gallstone formation and cholecystitis.

Interaction between doxorubicin and mitomycin C on mortality and myocardial contractility in guinea pig.

The present investigations were carried out in guinea pig to ascertain whether mitomycin C has a direct cardiotoxic effect or interacts with doxorubicin-induced cardiotoxicity. I.p. administration of mitomycin C did not modify the survival rate up to 30 days, whereas the combined administration of doxorubicin and mitomycin C significantly decreased the survival time in comparison to the doxorubicin-treated group. On isolated atria, mitomycin C did not cause significant inhibition of the contractile force or an enhancement of the doxorubicin-induced negative inotropic effect. These results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin.

Adenosine receptors mediating cardiac depression

Several adenosine analogs were evaluated for their effects on rate and contractility in guinea pig isolated atria. Among adenosine agonists, (−)-N-(1-methyl-2-phenylethyl) adenosine (ℓ-phenylisopropyladenosine; ℓ-PIA) and N-cyclohexyladenosine (CHA), decreased rate and force at nanomolar concentrations, whereas 2-chloroadenosine, N, N-dimethyladenosine (N 6-dimetyl-adenosine) and (+)-N-(1-methyl-2-phenylethyl) adenosine (d-phenyl-isopropyladenosine; d-PIA) were less potent cardiac depressants. The degree and order of potency of these agonists suggest that the cardiac depressant effects of adenosine are mediated via A 1-receptors. The cardiac depressant effects of CHA and ℓ-PIA were antagonized by theophylline and 1,3-diethyl-8-phenylxanthine (DPX).

Effects of physical training and thyroxine on rodent cardiac functional and biochemical properties.

The effects of 8 weeks of interval running and of 14 days of thyroxine treatment were studied on selected cardiac functional and biochemical parameters of contraction in both female guinea pigs and rats. Relative to their respective sendentary-control groups, both trained groups demonstrated typical exercise adaptations of resting bradycardia and of increases in skeletal muscle oxidative enzymes and relative heart mass (P less than 0.05). Myosin ATPase, Ca2+ regulated myofibril ATPase, and + dP/dt max were at least two-fold higher in rats compared to guinea pigs (P less than 0.001). Physical training did not augment any of these parameters in either species under the experimental conditions studied. However, biochemical and functional indices of intrinsic cardiac contractility in guinea pigs were increased by injections of thyroxine; whereas, the same treatment regimen was without effect on the rats. These findings suggest that chronic running does not alter the intrinsic cardiac contractility state in either species. Also, exercise doesn't change the thyroid state of the guinea pig to a level sufficient to affect cardiac function.