Abstract (EN):
The present investigation was undertaken to see whether a long-term inhibition of adenosine receptors - leading to hypertension - interferes with alpha(2)-adrenoceptor-mediated modulation of noradrenaline release. Rat tail arteries were removed from normal and from hypertensive animals obtained by chronic treatment with intraperitoneally infused DPSPX (1,3,dipropyl-8-sulphophenylxanthine) or orally administered L-NAME (N-G-Nitro-L-arginine methyl ester). To study prejunctional effects, the influence of UK-14,304 (5-bromo-6(imidazoline-2-ylamino)-quinoxaline) and yohimbine on the overflow of tritium evoked by electrical stimulation (100 V; 1 Hz; 2 ms; 5 min) from tissues preloaded with H-3-noradrenaline was analysed. To study postjunctional effects, concentration-response curves to UK-14,304 were determined. In DPSPX-treated rats there was an enhancement of the prejunctional effects of UK-14,304: its EC(30%) was reduced from 381 (250; 579) to 85 (73; 99) nmol.l(-1) (n = 5; P < 0.05) and its maximal effect - expressed as percent reduction of tritium overflow-increased from 45 +/- 5% to 61 +/- 5% (n = 6; P < 0.05). In L-NAME-treated rats there was no change in either of these two parameters. At the postjunctional level, there was no change in the sensitivity to UK-14,304 in tissues from either DPSPX- or L-NAME-treated rats. Yohimbine (10-1000 nmol.l(-1)) caused a concentration-dependent increase of tritium overflow evoked by electrical stimulation in both control and hypertensive animals (either DPSPX- or L-NAME-treated). The EC(50%)-pre-antagonist values (concentration of the antagonist that increases the evoked overflow by 50%) were not significantly different in the three situations. We conclude that long-term administration of DPSPX increases the sensitivity to the prejunctional effects of UK-14,304 without changing that to its postjunctional effects, showing a specific interaction between alpha-adrenoceptors and adenosine receptors at a prejunctional level. The question arises whether there is any link between that alteration and the development of the hypertensive state.
Language:
English
Type (Professor's evaluation):
Scientific
No. of pages:
4