Foster K A, Hock C E, Reibel D K
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
J Mol Cell Cardiol. 1991 Jan;23(1):91-101. doi: 10.1016/0022-2828(91)90042-k.
Inotropic responsiveness to alpha- and beta-adrenergic agents was examined in pressure-overload hypertrophied rat hearts. Pressure overload was induced in rats by abdominal aortic constriction. Three weeks post-constriction, hearts were isolated and perfused with buffer containing various concentrations of (1) calcium (2) isoproterenol (3) forskolin, or (4) phenylephrine. The change in rate of left ventricular pressure development (delta + dP/dt) with increasing perfusate calcium concentrations was comparable in hypertrophied hearts of aortic-constricted rats (AC) and hearts of sham-operated rats (SO). However, with isoproterenol or forskolin stimulation, inotropic responsiveness (delta + dP/dt) was 50% lower in hypertrophied hearts of AC. This was associated with significantly lower tissue cAMP levels. Beta-adrenoceptor number and affinity were unchanged in the hypertrophied myocardium. Maximum inotropic responsiveness to phenylephrine was also lower in hypertrophied hearts and was associated with reduced alpha-adrenoceptor numbers. The data suggest that altered inotropic responsiveness to alpha-adrenergic stimulation may, in part, be due to reduced cardiac alpha-adrenoceptor density. However, post-receptor mechanisms including alterations in cAMP metabolism may contribute to the reduced responsiveness to beta-adrenergic stimulation in hypertrophied hearts of AC.
在压力超负荷肥大的大鼠心脏中研究了对α和β肾上腺素能药物的变力反应性。通过腹主动脉缩窄在大鼠中诱导压力超负荷。缩窄三周后，分离心脏并用含有不同浓度的（1）钙、（2）异丙肾上腺素、（3）福斯可林或（4）去氧肾上腺素的缓冲液灌注。随着灌注液钙浓度增加，主动脉缩窄大鼠（AC）的肥大心脏和假手术大鼠（SO）的心脏中左心室压力发展速率（δ + dP/dt）的变化相当。然而，在异丙肾上腺素或福斯可林刺激下，AC肥大心脏中的变力反应性（δ + dP/dt）降低了50%。这与组织cAMP水平显著降低有关。肥大心肌中的β肾上腺素能受体数量和亲和力未发生变化。肥大心脏中对去氧肾上腺素的最大变力反应性也较低，并且与α肾上腺素能受体数量减少有关。数据表明，对α肾上腺素能刺激的变力反应性改变可能部分归因于心脏α肾上腺素能受体密度降低。然而，包括cAMP代谢改变在内的受体后机制可能导致AC肥大心脏中对β肾上腺素能刺激的反应性降低。
