摘要:

It is not clear how mitochondrial energy production is regulated in intact tissue when energy consumption suddenly changes. Whereas mitochondrial [NADH] ([NADH] sub m) may regulate cellular respiration rate and energetic state, it is not clear how [NADH]mitself is controlled during increased work in vivo. We have varied work and [Ca2+] in intact cardiac muscle while assessing [NADH]musing fluorescence spectroscopy. When increased work was accompanied by increasing average [Ca2+]c(by increasing [Ca2+]oor pacing frequency), [NADH]minitially fell and subsequently recovered to a new steady state level. Upon reduction of work, [NADH]movershot and then returned to control levels. In contrast, when work was increased without increasing average [Ca2+]c(by increasing sarcomere length), [NADH]mfell similarly, but no recovery or overshoot was observed. This Ca2+-dependent recovery and overshoot may be attributed to Ca sup 2+-dependent stimulation of mitochondrial dehydrogenases. We conclude that the immediate initial increase in respiration rate upon elevation of work is not activated by increased [NADH]m(since [NADH]mrapidly fell) or by [Ca2+]c(since work could also be increased at constant [Ca2+]c). However, during sustained high work, a Ca2+-dependent mechanism causes slow recovery of [NADH] sub m toward control values. This demonstrates a Ca2+-dependent feed-forward control mechanism of cellular energetics in cardiac muscle during increased work. (Circ Res. 1997;80:82-87.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

.05). Examination of myocardium from 1- and 3-month-old canines revealed that related differential changes to the spatiotemporal distribution of intercellular junctions occurred during postnatal maturation of the dog heart, suggesting that the process was not rodent specific. It is concluded that this progressive change in the organization and pattern of association between gap junctions and cell adhesion junctions is likely to be an important factor in maturation of electromechanical function within the mammalian heart. (Circ Res. 1997;80:88-94.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

.05). In myocytes superfused with bicarbonate-free buffer subjected to acid loading by NH4Cl pulsing, pH recovery (as measured by acid flux) was significantly stimulated by 3 micro mol/L LysoPC, indicative of NHE activation. Our study shows that cardiac injury produced by low concentrations of LysoPC can be effectively attenuated by NHE inhibition. The results also suggest that the beneficial effects of NHE inhibitors on the ischemic myocardium may be, at least partially, mediated by inhibiting the deleterious effects of LysoPC. (Circ Res. 1997;80:95-102.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Swelling-induced Cl sup - current (ICl.swell) is present in most cardiac tissues, but the unitary channel underlying ICl.swell is unknown. We used the cell-attached patch-clamp technique to assess the properties of single channels underlying ICl.swell and the basally active Cl sup - current (ICl.b) in rabbit atrial myocytes. Under isotonic conditions, single outwardly rectifying Cl sup - channels (ORCCs) with a slope conductance of 28 +/- 1 pS at the reversal potential were observed in 21 (5.7%) of 367 patches. Unconditional kinetic analysis revealed at least three open and four closed-channel states. Hypotonic superfusion-induced swelling resulted in the appearance of active channels in 41 (15.5%) of 265 patches without channel activity under isotonic conditions and caused a second active channel to appear in 3 of 14 patches showing a single channel under isotonic conditions. Overall, channels were seen in 54 of 336 patches under hypotonic conditions (16.1%, P<.001 versus isotonic conditions). The current-voltage relations, reversal potential-[Cl sup -]orelations, open probability, and kinetics of swelling-induced channels were indistinguishable from those of ORCCs under isotonic conditions. Unitary ORCCs, ICl.b, and ICl.swell were strongly and similarly inhibited by tamoxifen. Swelling-induced increases in macroscopic Cl sup - current were attributable to an increase in the number of active ORCCs with no significant effects on single-channel amplitude or open probability. Estimated macroscopic currents based on cell surface area, patch dimensions, single-channel ORCC current amplitude, open probability, and density were consistent with measured values of ICl.b and ICl.swell. We conclude that ORCCs underlie volume-regulated basal and swelling-induced Cl sup - currents in isolated rabbit atrial myocytes. (Circ Res. 1997;80:103-113.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists on baseline and atrial stretch-induced immunoreactive ANP (IR-ANP) and immunoreactive N-terminal ANP (IR-NT-ANP) release in vivo by using BQ-123 (ETAreceptor antagonist), bosentan (ETAand ETBreceptor antagonist), and losartan (AT1receptor antagonist). Intravenous administration of BQ-123 had no significant effect on baseline hemodynamics in conscious rats, whereas bosentan (10 mg/kg) and losartan (10 mg/kg) decreased slightly (4 to 7 mm Hg, P<.05 to .001) the mean arterial pressure. Both the ETAreceptor antagonist BQ-123 and ETA/ETBreceptor antagonist bosentan decreased plasma ANP and NT-ANP responses to volume load (P<.05 to .001), whereas the AT1receptor antagonist losartan had no significant effect on this response. The relative increase in plasma IR-ANP corresponding to a 3 mm Hg increase in right atrial pressure was 2.7-fold in the vehicle-treated group. BQ-123 (0.3 and 1.0 mg/kg) decreased this response 2.5- and 2.1-fold (P<.05); bosentan (3 and 10 mg/kg), 1.7-fold (P<.001) and 1.9-fold (P<.05); and bosentan (10 mg/kg)+losartan (10 mg/kg), 1.6-fold (P<.001). The responses in plasma IR-NT-ANP decreased simultaneously. These results indicate that combined inhibition of ETA/B and AT1receptors almost completely blocks ANP response to acute volume load. Therefore, our study shows that endogenous paracrine and/or autocrine factors liberated in response to atrial wall stretch rather than myocyte stretch itself are responsible for the activation of ANP peptide secretion in response to acute volume load. Our results also show that ETAreceptors are more important in the regulation of mechanical stretch-induced changes in cardiac hormone secretion than AT1receptors. (Circ Res. 1997;80:114-123.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A multicellular ventricular fiber model was used to determine mechanisms of slowed conduction and conduction failure during acute ischemia. We simulated the three major pathophysiological component conditions of acute ischemia: elevated [K sup +]o, acidosis, and anoxia. Elevated [K sup +]owas the major determinant of conduction, causing supernormal conduction, depressed conduction, and conduction block as [K sup +]owas gradually increased from 4.5 to 14.4 mmol/L. Only elevated [K sup +]ocaused conduction failure when varied within the range reported for acute ischemia. Before block, depressed upstrokes consisted of two distinct components: the first to the fast Na sup + current (INa) and the second to the L-type Ca sup 2+ current (ICa(L)). Even in highly depressed conduction, excitability was maintained by INa, with conduction block occurring at 95% INainactivation. However, because ICa(L) supported the later phase of the depressed upstroke, ICa(L) enhanced conduction and delayed block by increasing the electrotonic source current. At [K sup +]o=18 mmol/L, slow action potentials generated by ICa(L) were obtained with 10% ICa(L) augmentation. However, in the presence of acidosis and anoxia, significantly larger (120%) ICa(L) augmentation was required. The depressant effect was due mostly to anoxic activation of outward ATP-sensitive K sup + current, which counteracts inward ICa(L) and, by lowering the action potential amplitude, decreases the electrotonic current available to depolarize downstream cells. The simulations highlight the interactive nature of electrophysiological ischemic changes during propagation and demonstrate that both membrane changes and load factors (by downstream fiber) must be considered. (Circ Res. 1997;80:124-138.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH2-terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10 sup -9 mol/L and maximal activation at 10 sup -6 mol/L. Ang II activated JNK through the AT1receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca2+. Although the addition of either Ca2+ ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca2+ ionophore and phorbol ester markedly activated JNK. Slight expressions of the c-jun gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c-jun gene as well as the c-fos gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II-induced cardiac hypertrophy. (Circ Res. 1997;80:139-146.)

ISSN:0009-7330    

出版商:OVID    

年代:1997

数据来源: OVID