Vigue B, Ghaleh B, Giudicelli J F, Berdeaux A
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, France.
Fundam Clin Pharmacol. 1993;7(9):513-21. doi: 10.1111/j.1472-8206.1993.tb00255.x.
The aim of this study was to determine the relative roles of alpha 1-and alpha 2-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise in conscious dogs. The responses of left circumflex coronary artery diameter and blood flow were investigated at rest and during graded treadmill exercise (5, 10 and 12 km/h) in six chronically instrumented dogs during control conditions (saline) and after administration of propranolol (1 mg/kg) either alone or in combination with either prazosin (50 micrograms/kg), or idazoxan (300 micrograms/kg), or the association of prazosin+idazoxan (same doses). In control conditions, graded treadmill exercise resulted in a progressive increase in coronary artery diameter (+3.8 +/- 0.6% from 3479 +/- 80 microns) and in a decrease in coronary vascular resistance (-46.0 +/- 4.5% from 8.49 +/- 1.51 mmHg/cm/s). Propranolol significantly constricted large (-4.4 +/- 0.6% from 3486 +/- 87 microns) and limited dilation of small coronary arteries during exercise. These coronary effects of propranolol remained unchanged following additional alpha 2-adrenoceptor blockade by idazoxan but were abolished following alpha 1-adrenoceptor blockade by prazosin, given either alone or combined with idazoxan. Thus, alpha 1- but not alpha 2-adrenoceptors are responsible for propranolol-induced constriction of large coronary arteries and limitation of small coronary arteries dilation during exercise in conscious dogs.
本研究的目的是确定在清醒犬运动使交感神经张力增加时,α1和α2肾上腺素能受体在大的心外膜冠状动脉和小的阻力冠状动脉水平上的相对作用。在六只长期植入仪器的犬中,于对照条件下(生理盐水)以及单独给予普萘洛尔(1mg/kg)或与哌唑嗪(50μg/kg)、或咪唑克生(300μg/kg)、或哌唑嗪+咪唑克生联合用药(相同剂量)后,分别在静息状态和分级跑步机运动(5、10和12km/h)期间,研究左旋冠状动脉直径和血流的反应。在对照条件下,分级跑步机运动导致冠状动脉直径逐渐增加(从3479±80μm增加3.8±0.6%),冠状动脉血管阻力降低(从8.49±1.51mmHg/cm/s降低46.0±4.5%)。普萘洛尔显著收缩大冠状动脉(从3486±87μm收缩4.4±0.6%),并限制运动期间小冠状动脉的扩张。在给予咪唑克生额外阻断α2肾上腺素能受体后,普萘洛尔的这些冠状动脉效应保持不变,但在单独给予哌唑嗪或与咪唑克生联合给予哌唑嗪阻断α1肾上腺素能受体后,这些效应被消除。因此,在清醒犬运动期间,α1而非α2肾上腺素能受体负责普萘洛尔诱导的大冠状动脉收缩和小冠状动脉扩张受限。