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1.
Modulation of tea and tea polyphenols on benzo(a)pyrene-induced DNA damage in Chang liver cells 总被引:4,自引:0,他引:4
The protective effects of three tea extracts (green tea, GTE; oolong tea, OTE; and black tea, BTE) and five tea polyphenols (epicatechin, EC; epicatechin gallate, ECG; epigallocatechin, EGC; epigallocatechin gallate, EGCG; and theaflavins, THFs) on benzo[a]pyrene (B[a]P)-induced DNA damage in Chang liver cells were evaluated using the comet assay. B[a]P-induced DNA damage in Chang liver cells was significantly (p < 0.05) inhibited by GTE and OTE at a concentration of 10 microg/ml and by BTE at 25 microg/ml. At a concentration of 100 microg/ml, the % tail DNA was reduced from 33% (B[a]P treated only) to 10, 9, 13%, by GTE, OTE and BTE, respectively. EC and ECG did not cause DNA damage in cells according to the results of the comet assay; however, EGC, EGCG and theaflavins caused DNA damage in cells at a concentration of 100 microM. The results indicated that EC and ECG had protective effects against B[a]P-induced DNA damage in cells at a concentration of 10-100 microM. Although EGC, EGCG and the theaflavins caused DNA damage at a high concentration, but they had protective effects against B[a]P-induced DNA damage in cells at a low concentration of 10-50 microM. The results also showed that the DNA damage in cells induced by EGC, EGCG, and the theaflavins was due to the generation of superoxide during incubation with cells at a higher concentration. Therefore, tea catechins and THFs play an important role in enabling tea extracts to inhibit DNA damage in Chang liver cells. 相似文献
2.
Pinz I Tian R Belke D Swanson E Dillmann W Ingwall JS 《The Journal of biological chemistry》2011,286(12):10163-10168
The sarcoplasmic reticulum calcium ATPase (SERCA) plays a central role in regulating intracellular Ca(2+) homeostasis and myocardial contractility. Several studies show that improving Ca(2+) handling in hypertrophied rodent hearts by increasing SERCA activity results in enhanced contractile function. This suggests that SERCA is a potential target for gene therapy in cardiac hypertrophy and failure. However, it raises the issue of increased energy cost resulting from a higher ATPase activity. In this study, we determined whether SERCA overexpression alters the energy cost of increasing myocardial contraction in mouse hearts with pressure-overload hypertrophy using (31)P NMR spectroscopy. We isolated and perfused mouse hearts from wild-type (WT) and transgenic (TG) mice overexpressing the cardiac isoform of SERCA (SERCA2a) 8 weeks after ascending aortic constriction (left ventricular hypertrophy (LVH)) or sham operation. We found that overexpressing SERCA2a enhances myocardial contraction and relaxation in normal mouse hearts during inotropic stimulation with isoproterenol. Energy consumption was proportionate to the increase in contractile function. Thus, increasing SERCA2a expression in the normal heart allows an enhanced inotropic response with no compromise in energy supply and demand. However, this advantage was not sustained in LVH hearts in which the energetic status was compromised. Although the overexpression of SERCA2a prevented the down-regulation of SERCA protein in LVH hearts, TG-LVH hearts showed no increase in inotropic response when compared with WT-LVH hearts. Our results suggest that energy supply may be a limiting factor for the benefit of SERCA overexpression in hypertrophied hearts. Thus, strategies combining energetic support with increasing SERCA activity may improve the therapeutic effectiveness for heart failure. 相似文献
3.
Neuropeptide Y (NPY) reduces myocardial perfusion and inhibits the force of contraction of the isolated perfused rabbit heart 总被引:11,自引:0,他引:11
Isolated rabbit hearts, perfused under constant pressure (Langendorff technique) were used to study the effect of neuropeptide Y (NPY) on heart rate, force of heart contraction and rate of myocardial perfusion. No significant net change in heart rate was noted. A dose-dependent negative inotropic effect was consistently demonstrated which was characterised by slow onset and was often preceded by a transient positive inotropic response. Addition of small doses of NPY resulted in a prompt reduction in flow of the perfusate through the coronary vasculature. Since NPY is present locally in cardiac nerves, these effects may have physiological importance. 相似文献
4.
Preparative isolation and purification of theaflavins and catechins by high-speed countercurrent chromatography 总被引:1,自引:0,他引:1
Wang K Liu Z Huang JA Dong X Song L Pan Y liu F 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,867(2):282-286
High-speed countercurrent chromatography (HSCCC) has been applied for the separation of theaflavins and catechins. The HSCCC run was carried out with a two-phase solvent system composed of hexane-ethyl acetate-methanol-water-acetic acid (1:5:1:5:0.25, v/v) by eluting the lower aqueous phase at 2 ml/min at 700 rpm. The results indicated that pure theaflavin, theaflavins-3-gallate, theaflavins-3'-gallate and theaflavin-3,3'-digallate could be obtained from crude theaflavins sample and black tea. The structures of the isolated compounds were positively confirmed by (1)H NMR and (13)C NMR, MS analysis, HPLC data and TLC data. Meanwhile, catechins including epigallocatechin gallate, gallocatechin gallate, epicatechin gallate and epigallocatechin were isolated from the aqueous extract of green tea by using the same solvent system. This study developed a modified method combined with enrichment theaflavins method by using HSCCC for separation of four individual theaflavins, especially for better separation of theaflavins monogallates. 相似文献
5.
There is evidence that one or more metabolites of arachidonic acid can produce positive inotropic effects and may also be implicated in the enhanced alpha 1-adrenoceptor responses in hearts from diabetic rats. We therefore carried out a study to investigate the possibility that arachidonic acid metabolites could be involved in the altered cardiac alpha 1-effect of norepinephrine (in the presence of propranolol) in chronic streptozotocin-diabetic rats. Our results have shown that in the presence of the cyclooxygenase inhibitor indomethacin or the thromboxane synthetase inhibitor imidazole, the norepinephrine-stimulated positive inotropic effect and the formation of inositol 1,4,5-trisphosphate were significantly increased in control hearts but were unaltered in hearts from diabetic rats. The addition of the prostacyclin synthetase inhibitor tranylcypromine reduced the norepinephrine-stimulated positive inotropic effect and inositol 1,4,5-trisphosphate formation only in diabetic hearts and had no effect in the controls. The nature and physiological significance of the enhanced positive inotropic effect and inositol 1,4,5-trisphosphate formation in the control heart with the addition of indomethacin and imidazole are still unclear. The effect of tranylcypromine may indicate the participation of prostacyclin in mediating the enhanced alpha 1-inotropic effect of norepinephrine in the chronic diabetic heart. 相似文献
6.
Peroxidase-mediated oxidation of catechins 总被引:1,自引:0,他引:1
Theaflavins and thearubigins are major pigments in black tea, and they are produced by oxidation and polymerization of flavan-3-ols (catechins) during tea fermentation. In the course of studies on the mechanism of black tea polyphenol formation, we have systematically studied peroxidase-mediated oxidation of tea catechins. Individual catechins, appropriate pairs of catechins, and the combination of selected catechins and theaflavins have been used as substrates of peroxidase. Different dimers, trimers and a tetramer are formed. This work has led to the characterization of some of the new trimers in black tea by LC/ESI-MS/MS. The proposed mechanisms for the peroxidase-mediated reaction are discussed. 相似文献
7.
Antimicrobial Activities of Tocklai Vegetative Tea Clones 总被引:1,自引:0,他引:1
D. Thakur S. C. Das S. Sabhapondit P. Tamuly D. K. Deka 《Indian journal of microbiology》2011,51(4):450-455
Thirty-one Tocklai vegetative (TV) tea clones contained caffeine and total catechin 44.39 and 227.55 mg/g dry weight of leaves,
respectively. The (−)-epigallocatechin gallate (EGCG) was the most abundant (109.60 mg/g) followed by -(−)-epigallocatechin
(EGC, 44.54 mg/g), (−)-epicatechin gallate (ECG, 41.74 mg/g), (−)-epicatechin (EC, 27.42 mg/g) and +catechin (4.25 mg/g).
Total catechins were highest in TV 20 (509.7 mg/g) and lowest in TV 6 (71.7 mg/g). The tea clones that contain high level
of total catechin exhibited the strongest antimicrobial activity. Among caffeine and flavanol compounds, theaflavins (TF)
present in black tea possess a similar antimicrobial potency as EC present in fresh leaves, and that the conversion of catechins
to TF during fermentation in making black tea tends to alter their antimicrobial activities. The bioactive molecules other
than catechins present in tea leaves may also contribute towards antimicrobial activity. 相似文献
8.
Fumio Okada Tadakazu Takeo Shoji Okada Osamu Tamemasa 《Bioscience, biotechnology, and biochemistry》2013,77(5):791-794
Theaflavins, the oxidized products formed from tea leaf catechins during black tea fermentation, showed an antiviral activity on TMV. From the survey of the interactions of theaflavins with RNA and its related substances, it was presumed that theaflavins disturbed the replication cycle of TMV through binding to TMV-RNA. 相似文献
9.
M Karazyn D F Horrobin M S Manku S C Cunnane R A Karmali A I Ally R O Morgan K C Nicolaou W E Barnette 《Life sciences》1978,22(23):2079-2085
Prostacyclin when added to medium perfusing rat and rabbit hearts caused an increase in perfusion pressure at concentrations from 1 pg/ml ? 1 ng/ml (2.8 × 10?12 ? 2.8 × 10?9M) and a decrease at higher concentrations. Rhythm disturbances were observed with low prostacyclin concentrations in 6 of 10 rat hearts and 2 of 5 rabbit hearts studied. Increased heart rates were seen in the isolated rat hearts but not in the rabbit hearts. Force of contraction of isolated rat hearts was increased with increasing prostacyclin concentrations up to 100 pg/ml. Higher concentrations decreased contractile force. No inotropic effects were seen with rabbit hearts. 相似文献
10.
Paulus WJ Bronzwaer JG 《American journal of physiology. Heart and circulatory physiology》2004,287(1):H8-13
Beneficial actions of nitric oxide (NO) in failing myocardium have frequently been overshadowed by poorly documented negative inotropic effects mainly derived from in vitro cardiac preparations. NO's beneficial actions include control of myocardial energetics and improvement of left ventricular (LV) diastolic distensibility. In isolated cardiomyocytes, administration of NO increases their diastolic cell length consistent with a rightward shift of the passive length-tension relation. This shift is explained by cGMP-induced phosphorylation of troponin I, which prevents calcium-independent diastolic cross-bridge cycling and concomitant diastolic stiffening of the myocardium. Similar improvements in diastolic stiffness have been observed in isolated guinea pig hearts, in pacing-induced heart failure dogs, and in patients with dilated cardiomyopathy or aortic stenosis and have been shown to result in higher LV preload reserve and stroke work. NO also controls myocardial energetics through its effects on mitochondrial respiration, oxygen consumption, and substrate utilization. The effects of NO on diastolic LV performance appear to be synergistic with its effects on myocardial energetics through prevention of myocardial energy wastage induced by LV contraction against late-systolic reflected arterial pressure waves and through prevention of diastolic LV stiffening, which is essential for the maintenance of adequate subendocardial coronary perfusion. A drop in these concerted actions of NO on diastolic LV distensibility and on myocardial energetics could well be instrumental for the relentless deterioration of failing myocardium. 相似文献
11.
Theaflavins and thearubigins are major pigments in black tea, and it is generally accepted that they are produced by oxidation of flavan-3-ols (catechins) during tea fermentation. In the course of studies on the oxidation mechanism of tea polyphenols, especially the formation of thearubigins, a method combining the enzymatic synthesis and LC/ESI-MS/MS analysis was developed to search for new higher molecular weight polymers from black tea. Three new dibenzotropolones, theadibenzotropolone A, B, and C, together with one new tribenzotropolone, theatribenzotropolone A, were formed by the reaction of theaflavins and tea catechins with horseradish peroxidase in the presence of H(2)O(2). The structures of these new benzotropolone derivatives were elucidated on the basis of MS and 2D NMR spectroscopic analyses. The existence of these compounds in black tea was characterized by LC/ESI-MS/MS. Theadibenzotropolone A and B were the first benzotropolone-type trimers of catechins found in the black tea extract. The observation that galloyl ester groups of theaflavins can be oxidized to form di- or tri-benzotropolone skeletons strongly implied that this type of oxidation is an important pathway to extend the molecular size of thearubigins. 相似文献
12.
Tea polyphenols are strong antioxidants and are believed to have beneficial health effects. However, the blood and tissue levels of these compounds are not well characterized because of a lack of suitable analytical methods for the biological resolution of these compounds. Previously, we developed methods for the analysis of three green tea catechins. Now we report an improved method for the measurement of the levels of the different catechins and theaflavins in biological fluids and tissues. The method includes digestion of the plasma, urine, or tissue samples with beta-d-glucuronidase and sulfatase, followed by extraction with ethyl acetate and subsequent separation by reversed-phase high-performance liquid chromatography (HPLC). The polyphenols are identified on the basis of their retention times, spectral analysis, and electrochemical behavior across an array of electrodes. In a single HPLC run, it is possible to determine the major catechins and theaflavins as well as some of the catechin metabolites. The detection limits for catechins and theaflavins are from 5 to 10 ng/ml of saliva, plasma, or urine. 相似文献
13.
M A Clay P Stewart-Richardson D M Tasset J F Williams 《Biochemistry international》1988,17(5):791-800
The effects of ribose on the pre- and post-ischaemic functional performance of the isolated working heart from 24 month old chronically alcoholic animals was investigated. The improved perfusion model permitted the isolated heart to perform work analogous to that of the normal physiological load, in a system where systemic pressure and atrial pressure could be altered over a wide range and oxygen loss from the perfusion fluid was a minimum. There was a remarkable improvement in the performance of isolated hearts taken from alcoholic animals that were perfused with 1.7 mM ribose both before and after a 25.0 min period of global myocardial ischaemia (at 25 degrees C), however ribose treatment did not greatly affect the performance of hearts of isocaloric control aged rats. Chronic alcohol consumption significantly affected heart performance, causing a marked reduction in both cardiac and work output. After ischaemia the work of all hearts was notably decreased; there was no work output in untreated hearts of alcoholic animals, whereas in hearts of alcoholic animals treated with ribose work output was only decreased by 35%. The acute response to ribose by hearts of aged chronically alcoholic animals suggests a role for this compound as a positive inotropic agent and clearly indicates the beneficial potential of ribose for inclusion in cardioplegic solutions or for infusion in alcoholic subjects showing signs of heart failure or chronic heart disease. 相似文献
14.
A Sawamura N Sperelakis J Azuma S Kishimoto 《Canadian journal of physiology and pharmacology》1986,64(5):649-655
The effect of taurine (2-aminoethanesulphonic acid) on myocardial slow action potentials (APs) and accompanying contractions was examined in isolated perfused chick hearts and reaggregated cultured cells. Isoproterenol (ISO), histamine (HIS), or tetraethylammonium (TEA) induced slow APs and contractions in hearts whose fast Na+ channels had been inactivated by elevated K+. Taurine (10 mM) not only failed to induce slow APs, but actually decreased ISO (10(-8) M), HIS (10(-4) M), or TEA (10 mM) induced slow APs and contractions transiently (about 30s-2 min after the addition of taurine). The properties of the slow APs recovered to control levels by 7-13 min after the addition of the taurine; at this time, there was an increase in developed tension of the contraction accompanying the slow APs. These results suggest that the positive inotropic action of taurine is not mediated through an increase in the slow inward Ca2+ current. However, the transient depression of Ca2+-dependent slow APs by taurine probably explains the transient negative inotropic effect of taurine. 相似文献
15.
Oriji GK 《Prostaglandins, leukotrienes, and essential fatty acids》2000,63(6):343-349
Adenosine acts as a cardioprotective agent by producing coronary vasodilation, decreasing heart rate and by antagonizing the cardiostimulatory effect of catecholamines; adenosine also exerts a direct negative inotropic effect. Myocardial ischemia is known to be associated with enhanced levels of adenosine, increased protein kinase C (PKC) activity and prostacyclin (PGI2) release. The present study was conducted to determine if myocardial ischemia alters the cardioprotective effect of adenosine by increasing PKC activity and PGI2 release in the isolated rat heart perfused at 10 ml/min with Krebs-Henseleit buffer (KHB; 95% O2+5% CO2). Adenosine (10 mmol/min) reduced myocardial contractility as indicated by a decrease in contractility (dp/dtmax), heart rate (HR) and coronary perfusion pressure (PP). In hearts subjected to 30 min of ischemia (without perfusion) and then reperfused with KHB, adenosine failed to decrease dp/dtmax, HR or PP. However, during infusion of PKC inhibitor H-7 (1-(5-Isoquinolinesulfonyl)-2-methylpiperazine hydrochloride) (H-7; 6 mmol/min), which commenced 10 min before ischemia and continued throughout reperfusion, adenosine produced a decrease in dp/dtmax, HR and PP, similar to that before ischemia. Infusion of the PKC activator phorbol 12,13-dibutyrate (PDBu; 2 nmol/min) but not an inactive analogue in non-ischemic hearts prevented the adenosine induced decrease in dp/dtmax. During infusion of H-7, PDBu failed to block the direct negative inotropic effect of adenosine in non-ischemic hearts. In addition, pretreatment with H-7 or indomethacin (cyclooxygenase inhibitor) significantly reduced the PGI2 release following ischemia. This data suggest that PKC and PGI2 regulate the direct negative inotropic effect of adenosine, which is abolished during ischemia. 相似文献
16.
Kaygisiz Z Ozden H Erkasap N Koken T Gunduz T Ikizler M Kural T 《Acta physiologica Hungarica》2010,97(4):362-374
Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts. 相似文献
17.
Ischemia–reperfusion injury is a common complication of heart disease that is the leading cause of death worldwide. Here, we plan to elucidate oxytocin cardioprotection effects against ischemia–reperfusion via nitric oxide (NO), reactive oxygen species (ROS), and protein kinase C (PKC) in anesthetized rat preconditioned myocardium. Forty-eight Sprague-Dawley rats were equally divided into eight groups. All animals were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin (OT), L-NAME (LNA, a nitric oxide synthase inhibitor), chelerythrine (CHE, a PKC enzyme inhibitor), and N-acetylcysteine (NAC, a ROS scavenger) were used prior to ischemia. Results showed that mean arterial pressure significantly reduced during the first 10 min of ischemia and reperfusion in IR, LNA, CHE, and NAC groups (p < 0.05). OT prevented mean arterial pressure decline during early phase of ischemia and reperfusion. Cardioprotective effects of OT in infarct size, plasma levels of creatine kinase-MB and lactate dehydrogenase, severity and incidence of ventricular arrhythmias were abolished by L-NAME, chelerythrine, and N-acetylcysteine (p < 0.05). The present study showed that OT pretreatment reduces myocardial infarct size and ventricular arrhythmias, and improves mean arterial pressure via NO production, PKC activation, and ROS balance. These findings provide new insight into therapeutic strategies for ischemic heart disease. 相似文献
18.
Marin RM Franchini KG 《American journal of physiology. Heart and circulatory physiology》2005,289(1):H131-H136
In isolated rat hearts perfused with HEPES and red blood cell-enriched buffers, we examined changes in left ventricular pressure induced by increases in heart rate or infusion of adenosine to investigate whether the negative force-frequency relation and the positive inotropic effect of adenosine are related to an inadequate oxygen supply provided by crystalloid perfusates. Hearts perfused with HEPES buffer at a constant flow demonstrated a negative force-frequency relation, whereas hearts perfused with red blood cell-enriched buffer exhibited a positive force-frequency relation. In contrast, HEPES buffer-perfused hearts showed a concentration-dependent increase in left ventricular systolic pressure [EC50 = 7.0 +/- 1.2 nM, maximal effect (Emax) = 104 +/- 2 and 84 +/- 2 mmHg at 0.1 microM and baseline, respectively] in response to adenosine, whereas hearts perfused with red blood cell-enriched buffer showed no change in left ventricular pressure. The positive inotropic effect of adenosine correlated with the simultaneous reduction in heart rate (r = 0.67, P < 0.01; EC50 = 3.8 +/- 1.4 nM, baseline 228 +/- 21 beats/min to a minimum of 183 +/- 22 beats/min at 0.1 microM) and was abolished in isolated hearts paced to suppress the adenosine-induced bradycardia. In conclusion, these results indicate that the negative force-frequency relation and the positive inotropic effect of adenosine in the isolated rat heart are related to myocardial hypoxia, rather than functional peculiarities of the rat heart. 相似文献
19.
Tan J Maass DL White DJ Horton JW 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(2):R887-R896
This study examined the effects of major burn injury on the cellular distribution of several PKC isoforms in adult rat hearts and examined the hypothesis that PKC plays a regulatory role in cardiomyocyte cytokine secretion. Burn trauma was given over 40% total body surface area in Sprague-Dawley rats. An in vitro model of burn injury included addition of burn serum, 10% by volume, to primary cardiomyocyte cultures (collagen perfusion). In vivo burn injury produced redistribution of PKCdelta, PKCepsilon, and PKCalpha from the cytosol (soluble) to the membrane (particulate) component of the myocardium. This activation of the PKC isoforms was evident 2 h after burn injury and progressively increased over 24 h postburn. Addition of burn serum to isolated myocytes produced similar PKC isoform redistribution from the soluble to the particulate compartment, promoted myocyte Ca2+ and Na+ loading, and promoted robust myocyte secretion of inflammatory cytokines similar to that reported after in vivo burn injury. Pretreating cardiomyocytes with either calphostin or PKCepsilon inhibitory peptide, a potent inhibitor of PKCepsilon, prevented burn serum-related redistribution of the PKCepsilon isoform and prevented burn serum-related cardiomyocyte secretion of TNF-alpha, IL-1beta, IL-6, and IL-10. These data suggest that the PKCepsilon isoform plays a pivotal role in myocardial inflammatory response to injury, altering cardiac function by modulating cardiomyocyte inflammatory cytokine response to injury. 相似文献
20.
Haddad GE Coleman BR Zhao A Blackwell KN 《American journal of physiology. Heart and circulatory physiology》2005,288(2):H695-H704
ANG II plays a major role in development of cardiac hypertrophy through its AT1 receptor subtype, whereas angiotensin-converting enzyme (ACE) inhibitors are effective in reversing effects of ANG II on the heart. The objective of this study was to investigate the role of PKA and PKC in the contractile response of atrial tissue during development and ACE inhibitor-induced regression of eccentric hypertrophy induced by aortocaval shunt. At 1 wk after surgery, sham and shunt rats were divided into captopril-treated and untreated groups for 2 wk. Then isometric contraction was assessed by electrical stimulation of isolated rat left atrial preparations superfused with Tyrode solution in the presence or absence of specific inhibitors KT-5720 (for PKA) and Ro-32-0432 (for PKC) and high Ca2+. Peak tension developed was greater in shunt than in sham hearts. However, when expressed relative to tissue mass, hypertrophied muscle showed weaker contraction than muscle from sham rats. In sham rats, peak tension developed was more affected by PKC than by PKA inhibition, whereas this differential effect was reduced in the hypertrophied heart. Treatment of shunt rats with captopril regressed left atrial hypertrophy by 67% and restored PKC-PKA differential responsiveness toward sham levels. In the hypertrophied left atria, there was an increase in the velocity of contraction and relaxation that was not evident when expressed in specific relative terms. Treatment with ACE inhibitor increased the specific velocity of contraction, as well as its PKC sensitivity, in shunt rats. We conclude that ACE inhibition during eccentric cardiac hypertrophy produces a negative trophic and a positive inotropic effect, mainly through a PKC-dependent mechanism. 相似文献