Hypertension and enhanced beta-adrenoceptor-mediated facilitation of noradrenaline release produced by chronic blockade of adenosine receptors.

1. The study was undertaken to compare the beta-adrenoceptor-mediated facilitation of noradrenaline release in the tail artery of vehicle-treated rats and of rats rendered hypertensive by chronic administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX). Artery rings were loaded with [3H]-noradrenaline, and five periods of electrical stimulation (1 Hz for 2 min) were applied. To eliminate the influence of prejunctional alpha 2-adrenoceptors, the tissues were pre-exposed to 1 microM phenoxybenzamine. 2. Isoprenaline caused a concentration-dependent increase of tritium overflow elicited by electrical stimulation. It was more effective in arteries from DPSPX-treated than in those from vehicle-treated rats; isoprenaline (27.8 nM) increased by 30% tritium overflow in vessels from vehicle-treated rats whereas isoprenaline (7.0 nM) produced a 30% increase in vessels from DPSPX-treated animals. Furthermore, the maximal effect of isoprenaline was a 32.6% increase in control rats but a 48.6% increase in DPSPX-treated rats. 3. These results show that the sympathetic nerve endings of the rat tail artery are endowed with prejunctional beta-adrenoceptors which mediate facilitation of noradrenaline release elicited by electrical stimulation. They also suggest that adenosine receptors and beta-adrenoceptors interact at the prejunctional level and that impairment of this 'talk' may lead to the development of a hypertensive state.