ADRENALINE AND THE DEVELOPMENT OF SPONTANEOUS HYPERTENSION IN RATS

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Abstract
The effects of chronic alterations in plasma adrenaline [epinephrine] levels, on the development of a raised blood pressure in young spontaneously hypertensive (SHR) rats, were investigated. Bilateral adrenal demedullation (at 4 wk) significantly reduced plasma adrenaline levels and attenuated the development of hypertension. Pressor responses to phenylephrine (0.3-10 .mu.g, i.v.), measured in the pithed animals (11 wk after demedullation, were unaffected although neurogenic pressor responses were significantly reduced. S.c. implants of procaterol and salbutamol (0.005 and 0.165 .mu.mol/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 .mu.mol/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 .mu.mol/kg, s.c.) was abolished by treatment with the .beta.2-adrenoreceptor selective antagonist ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] (25 mg/kg per 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. 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.