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

Authors


Author for correspondence: Maria A. Vieira-Coelho, Faculty of Medicine, Institute of Pharmacology and Therapeutics, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal (fax +351 225516343, e-mail mavc@med.up.pt).

Abstract

Abstract:  In this study, we evaluated the effect of α2-adrenoceptor activation on catecholamine release from the adrenal medulla of pre-hypertensive (6-week-old) and hypertensive (16-week-old) spontaneously hypertensive rats (SHR) and of age-matched normotensive control Wistar Kyoto (WKY) rats. Catecholamine overflow from isolated adrenal medullae was evoked by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) in the absence and presence of the α2-adrenoceptor agonist medetomidine (MED). The spontaneous outflow of adrenaline was similar between age-matched SHR and WKY rats. However, the spontaneous outflow of noradrenaline was significantly lower in SHR compared with age-matched WKY rats. DMPP (0.1–3 mM) increased the outflow of noradrenaline and adrenaline in a concentration-dependent manner. The Emax values for adrenaline overflow were similar between strains, but the Emax values for noradrenaline overflow were significantly lower in SHR. The EC50 values for noradrenaline and adrenaline overflow were significantly higher in SHR compared with age-matched WKY rats. MED (0.1–300 nM) reduced the DMPP-evoked overflow (DMPP 500 μM) of noradrenaline and adrenaline in a concentration-dependent manner and was capable of totally inhibiting this effect. The inhibitory action of MED was similar between age-matched SHR and WKY rats. In the adrenals, the α2A- and α2B-adrenoceptor subtypes had the highest mRNA expression levels; the α2C-adrenoceptor subtype had the lowest mRNA expression levels. The mRNA levels for the three subtypes were similar between strains. In conclusion, in SHR during the development of hypertension, adrenal α2-adrenoceptor inhibitory function is conserved, accompanied by reduced noradrenaline release and unchanged adrenaline release.

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