Brown R A, Jefferson L, Sudan N, Lloyd T C, Ren J
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cell Mol Biol (Noisy-le-grand). 1999 Jun;45(4):453-65.
Acetaldehyde (ACA), the major metabolite of ethanol, exerts both stimulatory and depressive actions on myocardial tissue. We have recently shown that ACA depresses myocardial contraction, cardiac myocyte shortening and intracellular Ca2+ transients in normal rat heart. The purpose of the present study was to determine the influence of hypertension on ACA-induced myocardial actions. Mechanical properties of left ventricular papillary muscles and ventricular myocytes isolated from both 25-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were evaluated using force-transducer and video edge-detection, respectively. Papillary muscles and cardiac myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include: peak tension development (PTD), peak twitch amplitude (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening (RT90/TR90) and maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) depressed PTD without affecting other mechanical indices in both WKY and SHR myocardium, with maximal inhibition of 64 and 69%, respectively. SHR myocytes exhibited increased cell dimension, baseline PTA and resting intracellular Ca2+ levels, compared to WKY counterparts. ACA (0.03-30 mM) depressed PTA without affecting TPT, TR90 and +/-dL/dt. The maximal inhibitions were 31 and 36% in WKY and SHR groups, respectively. Interestingly, ACA exerted a biphasic effect on FFI, displaying potentiation at lower doses (<3 mM) and inhibition at higher doses (>3 mM). The maximal increase in FFI changes were 19 and 22% at 0.3 mM and the maximal decreases were 37 and 29% at 30 mM ACA, in WKY and SHR myocytes, respectively. Neither resting intracellular Ca2+ levels (FFI) nor fluorescence decay time (FDT) were affected by ACA. The increase in FFI was attenuated by propranolol (1 microM), whereas the decrease in FFI was reversed by BayK 8644 (1 microM). These results suggest that hypertension does not appear to alter ACA-induced myocardial depression. The mechanism underlying ACA-induced myocardial actions may involve increased beta-adrenergic activity at low doses and reduced Ca2+ entry and/or release at high doses.
乙醛（ACA）是乙醇的主要代谢产物，对心肌组织具有刺激和抑制作用。我们最近发现，ACA可抑制正常大鼠心脏的心肌收缩、心肌细胞缩短和细胞内Ca2+瞬变。本研究的目的是确定高血压对ACA诱导的心肌作用的影响。分别使用力传感器和视频边缘检测技术评估从25周龄的正常血压Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）分离的左心室乳头肌和心室肌细胞的力学特性。乳头肌和心肌细胞以0.5 Hz的频率进行电刺激以使其收缩。分析的收缩特性包括：峰值张力发展（PTD）､峰值抽搐幅度（PTA）､达到PTD/PTA的时间（TPT/TPS）､达到90%松弛/再延长的时间（RT90/TR90）以及收缩/缩短和松弛/再延长的最大速度（+/-VT/+/-dL/dt）。细胞内Ca2+瞬变以fura-2荧光强度（FFI）变化来测量。ACA（1 - 30 mM）抑制了WKY和SHR心肌中的PTD，但不影响其他力学指标，最大抑制率分别为64%和69%。与WKY心肌细胞相比，SHR心肌细胞的细胞尺寸、基线PTA和静息细胞内Ca2+水平增加。ACA（0.03 - 30 mM）抑制了PTA，但不影响TPT、TR90和+/-dL/dt。WKY组和SHR组的最大抑制率分别为31%和36%。有趣的是，ACA对FFI有双相作用，在较低剂量（<3 mM）时表现为增强，在较高剂量（>3 mM）时表现为抑制。在WKY和SHR心肌细胞中，在0.3 mM时FFI变化的最大增加分别为19%和22%，在30 mM ACA时最大减少分别为37%和29%。静息细胞内Ca2+水平（FFI）和荧光衰减时间（FDT）均不受ACA影响。普萘洛尔（1 microM）减弱了FFI的增加，而BayK 8644（1 microM）逆转了FFI的减少。这些结果表明，高血压似乎并未改变ACA诱导的心肌抑制作用。ACA诱导心肌作用的机制可能涉及低剂量时β-肾上腺素能活性增加以及高剂量时Ca2+内流和/或释放减少。
