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Basic Clin Pharmacol Toxicol ; 109(4): 253-60, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21518261

RESUMO

In this study, we evaluated the effect of α(2) -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 α(2) -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 E(max) values for adrenaline overflow were similar between strains, but the E(max) values for noradrenaline overflow were significantly lower in SHR. The EC(50) 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 α(2A)- and α(2B)-adrenoceptor subtypes had the highest mRNA expression levels; the α(2C)-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 α(2) -adrenoceptor inhibitory function is conserved, accompanied by reduced noradrenaline release and unchanged adrenaline release.


Assuntos
Medula Suprarrenal/metabolismo , Epinefrina/metabolismo , Hipertensão/metabolismo , Norepinefrina/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Medula Suprarrenal/efeitos dos fármacos , Animais , Iodeto de Dimetilfenilpiperazina/farmacologia , Hipertensão/patologia , Masculino , Medetomidina/farmacologia , Antagonistas Nicotínicos/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Adrenérgicos alfa 2/efeitos dos fármacos
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