Adrenaline and the Development of Spontaneous Hypertension in Rats

Abstract

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.

Studies on the anti‐vasoconstrictor activity of BRL 34915 in spontaneously hypertensive rats; a comparison with nifedipine

“…This suggests that increased cardiac output contributes little to the blood pressure response during brief periods of electrical activation of the spinal sympathetic outflow, at least in the absence of the adrenal medullae. Secondly, on the question of a role for the adrenal medullae, although both Yamaguchi & Kopin (1979) and Borkowski & Quinn (1985) have shown that adrenal-demedullation of rats several weeks beforehand, produced a modest reduction in the size of frequency-dependent pressor responses after pithing, the latter authors reported that a major proportion of this inhibition was attributable to a loss of adrenaline-mediated facilitation of sympathetic neurotransmission via excitation of prejunctional #2-adrenoceptors. The contribution of adrenaline to frequency-dependent pressor responses via this facilitatory mechanism may well have been blocked in the present experiments by our use of the f2-adrenoceptor selective antagonist, ICI 118,551.…”

Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension

“…They are also an important component of the HPA axis as part of the body's response to stress, acting upon the adrenal medulla to regulate the biosynthesis and secretion of the catecholamine epinephrine, a neurotransmitter/neurohormone that is physiologically significant in the sympathetic control of blood pressure and cardiovascular activity (Borkowski & Quinn 1984, Wong 2006. Its synthesis and release is regulated by the HPA and SA axes during the neuroendocrine response to stress (Axelrod 1976, Wong 2006.…”

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

“…Hypertension and left ventricular hypertrophy were absent only in sympathectomized SHR that were subjected to adrenal demedullation [15,16]. Studies have also shown that the development of hypertension is attenuated in young SHR subjected to adrenal demedullation [17,18] and that the development of hypertension is restored by chronic adrenaline supplementation [19]. However, we have previously shown that in SHR before (6 weeks of age) and during the development of high blood pressure (12 and 22 weeks of age) not only are adrenal catecholamine content and synthesis reduced but also that adrenaline plasma levels are similar compared with those found in the normotensive control Wistar Kyoto (WKY) rats [20].…”