Borkowski K R, Quinn P
J Auton Pharmacol. 1985 Jun;5(2):89-100. doi: 10.1111/j.1474-8673.1985.tb00109.x.
The effects of chronic alterations in plasma adrenaline levels, on the development of a raised blood pressure in young spontaneously hypertensive (SHR) rats, have been investigated. Bilateral adrenal demedullation (at 4 weeks) significantly reduced plasma adrenaline levels and attenuated the development of hypertension. Pressor responses to phenylephrine (0.3-10 micrograms, i.v.), measured in the pithed animals 11 weeks after demedullation, were unaffected although neurogenic pressor responses were significantly reduced. Subcutaneous implants of procaterol and salbutamol (0.005 and 0.165 mumol/kg, respectively) restored hypertension development in demedullated rats and significantly enhanced neurogenic pressor responses, while responses to i.v. phenylephrine remained unaltered, in the pithed rats. Implants of adrenaline (0.165 and 0.5 mumol/kg, s.c.) also restored hypertension development. However, pressor responses to phenylephrine were reduced and neurogenic responses only slightly enhanced when compared to those obtained in untreated pithed demedullated rats. The pro-hypertensive effect of adrenaline (0.5 mumol/kg, s.c.) was abolished by treatment with the beta 2-adrenoreceptor selective antagonist ICI 118551 (25 mg/kg/day, p.o.). In the subsequently pithed rats, neurogenic pressor responses were slightly reduced when compared to those in animals treated with adrenaline alone. In control demedullated rats, ICI 118551 had no effect on blood pressure nor on the neurogenic and phenylephrine-induced pressor responses. However, in sham-operated animals, ICI 118551 attenuated the development of hypertension and significantly reduced neurogenic pressor responses in the subsequently pithed rats. Responses to phenylephrine remained unaltered. The results support the suggestion that a beta 2-adrenoreceptor-mediated facilitation of sympathetic neurotransmission may be involved in mediating the pro-hypertensive effects of circulating adrenaline in the SHR rat.
研究了血浆肾上腺素水平的长期改变对年轻自发性高血压（SHR）大鼠血压升高发展的影响。双侧肾上腺髓质切除术（4周时）显著降低了血浆肾上腺素水平，并减弱了高血压的发展。去髓质11周后，在脊髓横断动物中测量的对去氧肾上腺素（0.3 - 10微克，静脉注射）的升压反应未受影响，尽管神经源性升压反应显著降低。皮下植入丙卡特罗和沙丁胺醇（分别为0.005和0.165微摩尔/千克）恢复了去髓质大鼠的高血压发展，并显著增强了神经源性升压反应，而在脊髓横断大鼠中，对静脉注射去氧肾上腺素的反应保持不变。肾上腺素（0.165和0.5微摩尔/千克，皮下注射）植入物也恢复了高血压发展。然而，与未处理的脊髓横断去髓质大鼠相比，对去氧肾上腺素的升压反应降低，神经源性反应仅略有增强。肾上腺素（0.5微摩尔/千克，皮下注射）的升压作用被β2 - 肾上腺素能受体选择性拮抗剂ICI 118551（25毫克/千克/天，口服）治疗所消除。在随后脊髓横断的大鼠中，与仅用肾上腺素治疗的动物相比，神经源性升压反应略有降低。在对照去髓质大鼠中，ICI 118551对血压以及神经源性和去氧肾上腺素诱导的升压反应均无影响。然而，在假手术动物中，ICI 118551减弱了高血压的发展，并显著降低了随后脊髓横断大鼠的神经源性升压反应。对去氧肾上腺素的反应保持不变。结果支持这样的观点，即β2 - 肾上腺素能受体介导的交感神经传递促进作用可能参与介导SHR大鼠循环肾上腺素的升压作用。
