Hieble J P, McCafferty J P, Roesler J M, Pendleton R G, Gessner G, Carey R, Sarau H M, Goldstein M
J Cardiovasc Pharmacol. 1983 Sep-Oct;5(5):889-97. doi: 10.1097/00005344-198309000-00029.
SK&F 64139 (7,8-dichloro-1,2,3,4-tetrahydroisoquinoline) produces a dose-related antihypertensive effect in rats treated with desoxycorticosterone acetate and administered saline in their drinking water (DOCA-salt rats), lowering both systolic and diastolic blood pressure by 40 mm Hg after an oral dose of 25 mg/kg in a conscious animal. This antihypertensive effect can also be observed after intravenous infusion in an anesthetized DOCA rat. The fall in blood pressure is accompanied by bradycardia, which can be blocked by the combination of propranolol plus vagotomy, and a decrease in peripheral vascular resistance. In contrast to the results in the DOCA rat, only minimal effects on blood pressure were produced in normotensive rats. Although SK&F 64139 is a potent inhibitor of phenylethanolamine N-methyltransferase (PNMT), the time course of blood pressure reduction is not consistent with PNMT inhibition as a mechanism for its antihypertensive action. SK&F 64139 decreases the turnover rate of cardiac norepinephrine in DOCA-salt rats, suggesting that its antihypertensive effect may results from a centrally mediated inhibition of sympathetic outflow to the periphery.
SK&F 64139（7,8 - 二氯 - 1,2,3,4 - 四氢异喹啉）在给予醋酸去氧皮质酮并饮用盐水的大鼠（DOCA - 盐大鼠）中产生剂量相关的降压作用，在清醒动物口服25mg/kg剂量后，收缩压和舒张压均降低40mmHg。在麻醉的DOCA大鼠中静脉输注后也可观察到这种降压作用。血压下降伴随着心动过缓，普萘洛尔加迷走神经切断术的联合应用可阻断这种心动过缓，同时外周血管阻力降低。与DOCA大鼠的结果相反，SK&F 64139对正常血压大鼠的血压仅有极小的影响。尽管SK&F 64139是苯乙醇胺N - 甲基转移酶（PNMT）的强效抑制剂，但其血压降低的时间进程与作为降压作用机制的PNMT抑制作用不一致。SK&F 64139降低了DOCA - 盐大鼠心脏去甲肾上腺素的周转速率，提示其降压作用可能源于中枢介导的对交感神经向外周输出的抑制。
