Long-term administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX) alters alpha 2-adrenoceptor-mediated effects at the pre- but not at the postjunctional level.
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 (NG-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 3H-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 Ec30% 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Guimarães
S
S
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Paiva
M Q
MQ
Moura
D
D
Vaz-da-Silva
M J
MJ
Albino-Teixeira
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D000068438:Brimonidine Tartrate; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009451:Neuroeffector Junction / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000098:blood supply; D014970:Xanthines / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D018047:Receptors, Purinergic P1; D014970:Xanthines; D000068438:Brimonidine Tartrate; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester