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.
Guimarães
S
S
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Albino-Teixeira
A
A
Paiva
M Q
MQ
D000818:Animals; D001158:Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013623:Tail / Q000098:blood supply; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D014970:Xanthines; D010643:Phenoxybenzamine; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D007545:Isoproterenol; D009638:Norepinephrine