Antonaccio M J, High J, DeForrest J M, Sybertz E
J Pharmacol Exp Ther. 1986 Jul;238(1):378-87.
Twelve beta adrenoceptor antagonists were examined for their effects on mean blood pressure (MBP), heart rate (HR), plasma renin activity (PRA) and sympathetic nerve function in spontaneously hypertensive rats (SHR). The selected drugs included cardioselective agents (acebutolol, atenolol and metoprolol), agents with intrinsic sympathomimetic activity (oxprenolol, acebutolol, alprenolol and pindolol) and agents with local anesthetic activity (propranolol, oxprenolol, acebutolol, alprenolol and labetalol). All 12 beta adrenoceptor antagonists, administered once daily for 4 days (30 mg/kg p.o.), significantly decreased MBP of SHR. This reduction in MBP was dissociable from both reductions in HR as well as peripheral beta adrenoceptor blockade. In addition, the onset of MBP reduction was slower than the onset of beta adrenoceptor blockade and became greater with duration of treatment. PRA activity was significantly and markedly reduced by both bunolol and metoprolol shortly after dosing at a time when HR was significantly reduced but MBP was not. Conversely, at a time when MBP was significantly reduced by both bunolol and metoprolol, PRA and HR were found to be normal. The changes in HR and PRA were correlated with peripheral beta adrenoceptor blockade but changes in MBP were not. Bunolol, metoprolol and propranolol had no consistent inhibitory effect on pressor responses to nerve stimulation in pithed SHR, although positive chronotropic responses to norepinephrine, tyramine, dimethylphenylpiperazinium and angiotensin I and II were significantly and markedly reduced. It is concluded that beta adrenoceptor antagonists, as a class, reduce MBP of conscious SHR, provided that sufficient time is allowed for this observation to occur. Furthermore, the reduction in MBP caused by beta adrenoceptor antagonists is unrelated to acute beta adrenoceptor blockade, changes in HR, reductions in PRA or inhibition of sympathetic nerve function. Finally, cardioselectivity, intrinsic sympathomimetric activity and local anesthetic activity are not required for the antihypertensive activity of these agents.
研究了12种β肾上腺素能受体拮抗剂对自发性高血压大鼠（SHR）平均血压（MBP）、心率（HR）、血浆肾素活性（PRA）和交感神经功能的影响。所选药物包括心脏选择性药物（醋丁洛尔、阿替洛尔和美托洛尔）、具有内在拟交感活性的药物（氧烯洛尔、醋丁洛尔、阿普洛尔和吲哚洛尔）以及具有局部麻醉活性的药物（普萘洛尔、氧烯洛尔、醋丁洛尔、阿普洛尔和拉贝洛尔）。所有12种β肾上腺素能受体拮抗剂每日口服给药1次，连续给药4天（30mg/kg），均能显著降低SHR的MBP。MBP的降低与HR的降低以及外周β肾上腺素能受体阻滞均无关。此外，MBP降低的起效时间比β肾上腺素能受体阻滞的起效时间慢，且随着治疗时间的延长而增大。在给药后不久，布诺洛尔和美托洛尔在显著降低HR但未降低MBP时，能显著且明显降低PRA活性。相反，当布诺洛尔和美托洛尔均显著降低MBP时，PRA和HR均正常。HR和PRA的变化与外周β肾上腺素能受体阻滞相关，但MBP的变化与之无关。布诺洛尔、美托洛尔和普萘洛尔对去脑SHR对神经刺激的升压反应没有一致的抑制作用，尽管对去甲肾上腺素、酪胺、二甲基苯基哌嗪鎓以及血管紧张素I和II的正性变时反应均显著且明显降低。得出结论，只要有足够时间进行观察，β肾上腺素能受体拮抗剂作为一类药物可降低清醒SHR的MBP。此外，β肾上腺素能受体拮抗剂引起的MBP降低与急性β肾上腺素能受体阻滞、HR变化、PRA降低或交感神经功能抑制无关。最后，这些药物的降压活性不需要心脏选择性、内在拟交感活性和局部麻醉活性。
