Li K, Stewart D J, Rouleau J L
Research Center, Centre Hospitalier de l'Université de Sherbrooke, Canada.
Circ Res. 1991 Aug;69(2):301-12. doi: 10.1161/01.res.69.2.301.
The actions of endothelin on the contractile and twitch configuration characteristics of rat and rabbit papillary muscles were evaluated before and after endocardial endothelium removal. In rabbit papillary muscles, endothelin produced a dose-dependent (10(-11) to 10(-7) M) increase in tension (T) (from 2.7 +/- 0.2 to 8.9 +/- 0.7 g/mm2, p less than 0.01), dT/dt, and Vmax (from 1.14 +/- 0.03 to 3.0 +/- 0.13 Lmax/sec, p less than 0.01), a decrease in time to peak tension (from 251 +/- 9 to 216 +/- 7 msec, p less than 0.05), and an increase in time to half relaxation (from 168 +/- 9 to 293 +/- 14 msec, p less than 0.01). Increasing calcium concentration in the bath from 1.25 to 15 mM greatly attenuated these changes. In the presence of propranolol (10(-5) M), endothelin increased all indexes of contractility but to a lesser extent (T = 2.6 +/- 0.3 to 6.5 +/- 0.2 g/mm2, p less than 0.01; Vmax = 1.16 +/- 0.10 to 2.06 +/- 0.10 Lmax/sec, p less than 0.01). Myocardial catecholamine depletion with reserpine had effects similar to those of propranolol. The myocardial contractile and twitch configuration characteristics of endothelin were similar to those of phenylephrine (10(-4) M), a strong stimulator of the phosphatidylinositol pathway and a moderate beta-adrenergic stimulator. The effects of phenylephrine and endothelin were modified in a similar manner by propranolol (10(-5) M). The presence of nicardipine (3 X 10(-7) M) decreased the absolute increase in contractility caused by endothelin but did not alter the percent change or shift the dose-response curve of endothelin. The actions of endothelin in rat papillary muscles studied at physiological calcium concentrations (Ca2+ = 1.25 mM) were less marked than those of rabbit studied at physiological calcium (Ca2+ = 1.25 mM) but similar to those of rabbit studied at high calcium concentrations (Ca2+ = 15 mM). Removing the endocardial endothelial layer of rabbit papillary muscles did not alter the absolute changes in contractility caused by endothelin but shifted the dose-response curve to the left and markedly altered the effects of endothelin on twitch configuration characteristics. Thus, it would appear that endothelin increases contractility and modifies twitch configuration. It does so more at lower rather than higher extracellular calcium concentrations and in a species, such as rabbit, that responds more to interventions that increase intracellular calcium.(ABSTRACT TRUNCATED AT 400 WORDS)
在内皮剥脱前后，评估了内皮素对大鼠和家兔乳头肌收缩及抽搐形态特征的作用。在家兔乳头肌中，内皮素产生剂量依赖性（10⁻¹¹至10⁻⁷M）的张力（T）增加（从2.7±0.2增至8.9±0.7g/mm²，p<0.01）、dT/dt增加以及Vmax增加（从1.14±0.03增至3.0±0.13Lmax/秒，p<0.01），达到峰值张力的时间减少（从251±9减至216±7毫秒，p<0.05），而弛豫至一半的时间增加（从168±9增至293±14毫秒，p<0.01）。将浴槽中钙浓度从1.25mM增至15mM可极大地减弱这些变化。在普萘洛尔（10⁻⁵M）存在的情况下，内皮素增加了所有收缩性指标，但程度较小（T = 2.6±0.3至6.5±0.2g/mm²，p<0.01；Vmax = 1.16±0.10至2.06±0.10Lmax/秒，p<0.01）。利血平使心肌儿茶酚胺耗竭产生的作用与普萘洛尔相似。内皮素的心肌收缩及抽搐形态特征与去氧肾上腺素（10⁻⁴M）相似，去氧肾上腺素是磷脂酰肌醇途径的强刺激剂及中度β-肾上腺素能刺激剂。普萘洛尔（10⁻⁵M）以类似方式改变了去氧肾上腺素和内皮素的作用。尼卡地平（3×10⁻⁷M）的存在减少了内皮素引起的收缩性绝对增加，但未改变百分比变化或使内皮素的剂量-反应曲线发生偏移。在生理钙浓度（Ca²⁺ = 1.25mM）下研究的大鼠乳头肌中，内皮素的作用不如在生理钙（Ca²⁺ = 1.25mM）下研究的家兔明显，但与在高钙浓度（Ca²⁺ = 15mM）下研究的家兔相似。去除家兔乳头肌的心内膜内皮层并未改变内皮素引起的收缩性绝对变化，但使剂量-反应曲线向左移动，并显著改变了内皮素对抽搐形态特征的作用。因此，似乎内皮素增加收缩性并改变抽搐形态。在较低而非较高的细胞外钙浓度下以及在对增加细胞内钙的干预反应更强的物种（如家兔）中，内皮素的作用更明显。（摘要截短于400字）
