Green M A, Egle J L
Toxicol Appl Pharmacol. 1983 Jun 15;69(1):29-36. doi: 10.1016/0041-008x(83)90115-1.
These experiments were undertaken to study the effect of the interaction of the antihypertensive agent guanethidine and two aldehydes possessing sympathomimetic activity on the blood pressure of spontaneously hypertensive rats (SHR). Acetaldehyde, when administered iv to acutely guanethidine-pretreated (15 mg/kg) SHRs under urethane anesthesia, caused a potentiated pressor response in the dose range of 3 to 40 mg/kg. When administered iv to chronically guanethidine-pretreated SHRs, a pressor response was noted at low doses and a depressor response at high doses. Acrolein (0.05 to 0.5 mg/kg) produced a pressor response at low doses and a depressor response at high doses in both acutely and chronically guanethidine-pretreated SHRs. Pressor responses, particularly to acetaldehyde, may be due to an enlarged tyramine-releasable pool, hyperreactivity of alpha adrenergic receptors of SHRs, or guanethidine inhibition of norepinephrine reuptake. Depressor responses to high doses of aldehydes may be attributed to vagal stimulation or direct vasodilation. It is concluded that there is a significant interaction between the aldehydes and guanethidine which may have implications for someone undergoing treatment with guanethidine for hypertension while being exposed to acetaldehyde and related compounds from ethanol and tobacco smoke.
进行这些实验是为了研究抗高血压药物胍乙啶与两种具有拟交感神经活性的醛相互作用对自发性高血压大鼠(SHR)血压的影响。在氨基甲酸乙酯麻醉下,给急性用胍乙啶预处理(15毫克/千克)的SHR静脉注射乙醛,在3至40毫克/千克的剂量范围内会引起升压反应增强。给慢性用胍乙啶预处理的SHR静脉注射时,低剂量时出现升压反应,高剂量时出现降压反应。在急性和慢性用胍乙啶预处理的SHR中,丙烯醛(0.05至0.5毫克/千克)在低剂量时产生升压反应,在高剂量时产生降压反应。升压反应,尤其是对乙醛的反应,可能是由于可释放酪胺的池扩大、SHR的α肾上腺素能受体反应性过高或胍乙啶对去甲肾上腺素再摄取的抑制。对高剂量醛的降压反应可能归因于迷走神经刺激或直接血管舒张。得出的结论是,醛与胍乙啶之间存在显著的相互作用,这可能对正在接受胍乙啶治疗高血压同时又接触来自乙醇和烟草烟雾中的乙醛及相关化合物的人有影响。