Wexler B C
Br J Exp Pathol. 1985 Apr;66(2):143-54.
Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.
选用成年雌雄正常血压的斯普拉格-道利（S-D）大鼠和自发性高血压大鼠（SHR），每日三次注射普萘洛尔，持续3周。注射终止后，无一动物出现戒断症状。7天后，给动物注射一剂异丙肾上腺素，这会在未治疗的动物中导致大面积心肌梗死和50 - 60%的死亡率。普萘洛尔预处理仅在SHR中产生明显的镇静和降压作用。尽管有7天的普萘洛尔撤药期，但很少有动物死亡，心肌损伤也很轻微。然而，血压水平降至休克样水平，血液中肌酸磷酸激酶（CPK）和乳酸脱氢酶（LDH）水平呈动态升高，出现明显的高甘油三酯血症，血浆皮质酮升至超正常水平。显微镜下，普萘洛尔预处理动物的心脏几乎没有坏死迹象，但SHR心脏出现大量心房和心室血栓。提示在大鼠中，普萘洛尔治疗通过激素和代谢变化介导产生积极的心肌保护作用，且普萘洛尔撤药不会导致对儿茶酚胺的超敏反应。事实上，普萘洛尔的β受体阻断作用在撤药后仍能在一段时间内保持有效。
