Effects of medullary α2-adrenoceptor blockade in the rat

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The effect of α2-adrenoceptor blockade in the medulla was studied in pentobarbital anesthetized rats in which arterial blood pressure, heart rate and renal sympathetic nerve activity were analysed. Three series of experiments were performed: (1) i.c. administration of α2-adrenoceptor antagonists with different subtype affinities; (2) i.v. administration of methoxy-idazoxan to study its effects on neuronal activity into the rostral ventral medulla; (3) microinjections of methoxy-idazoxan in rostral ventral medulla and nucleus tractus solitarii. Methoxy-idazoxan (0.1–3 μg kg−1 i.c., n=5), but not saline, rauwolscine, BRL 44408 (2-[2H-(1,3,dihydroisoindol)methyl]-4,5dihydroimidazol) or ARC 239 (2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquilindione) (each at 10–100 μg kg−1 i.c., n=5–5–6–5, respectively), increased mean arterial blood pressure, heart rate and renal nerve activity (+19±6 mm Hg, +72±22 beats min−1, +43±9%) and blocked the sympatho-inhibitory action of clonidine (10 μg kg−1 i.v.). In further experiments, methoxy-idazoxan, BRL 44408 and the highest dose of rauwolscine i.c., reversed the clonidine-induced sympatho-inhibition (order of potency: methoxy-idazoxan>BRL4440>rauwolscine, n=6 each), whereas ARC 239 (n=5) or saline (n=7) did not. Methoxy-idazoxan i.v. (n=7, 10–100 μg kg−1) increased the renal sympathetic nerve and rostral ventral medulla neuronal activity and the heart rate (+36±7%, +66±29% and +18±9 beats min−1) without a significant effect on mean arterial blood pressure. Microinjection of methoxy-idazoxan (1 nmol/40 nl) into the rostral ventral medulla reversed the effect of clonidine microinjected into the same site (2 nmol/40 nl, n=5). In another group of rats (n=8), methoxy-idazoxan increased mean arterial blood pressure, heart rate and renal nerve activity (+16±2 mm Hg, +42±7 beats min−1, +24±5%) and blocked the effect of clonidine i.v. (10 μg kg−1). Bilateral microinjections into the nucleus tractus solitarii (n=5) did not alter mean arterial blood pressure but decreased heart rate and sympathetic nerve activity (−30±16 beats min−1, −20±14%). Our results offer direct in vivo evidence for the main role of the α2A/D-adrenoceptors located in the ventral pressor area. The data show that the sympathy-excitatory effect of α2-adrenoceptor antagonists is due to the blockade of a tonic activation of these α2A/D-adrenoceptors present in the rostral ventral pressor area.