Endothelium-dependent vascular responses in 1,3-dipropyl-8-sulphophenylxanthine (DPSPX) hypertensive rats.
The study was undertaken to test the endothelium-mediated vascular responses in rats rendered hypertensive by chronic administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX). The relaxant effect of carbachol (an endothelium-dependent relaxing drug) and of sodium nitroprusside (an endothelium-independent relaxing drug) as well as the potentiation of the contractile effect of noradrenaline by NG-nitro-L-arginine methyl ester (L-NAME) were compared in aortic rings from normotensive and DPSPX-hypertensive rats. Carbachol and sodium nitroprusside caused concentration-dependent relaxations in aortic rings precontracted by 1 microM noradrenaline. The relaxant effect being of carbachol was significantly reduced in tissues of DPSPX-hypertensive rats: the maximal relaxant effect being 86 +/- 3% and 64 +/- 4% (of the pre-existing tone) in normal and hypertensive rats, respectively, while there were no significant differences in the relaxant effect of sodium nitroprusside. L-NAME (100 microM) significantly reduced the EC50 values of noradrenaline (3.71 +/- 0.28 times, n = 8 and 2.96 +/- 0.27 times, n = 7, in normal and hypertensive rats, respectively) and significantly enhanced the maximal contractile effect of noradrenaline (46 +/- 8%, n = 8 and 35 +/- 6%, n = 7, in normal and hypertensive rats respectively): the factors of reduction of EC50 values and the percentages of enhancement of the maximal contractile effect in the aorta of normal and hypertensive rats were not significantly different. The results obtained provide evidence of functional impairment of the endothelium in DPSPX-hypertensive rats.
Paiva
M Q
MQ
Institute of Pharmacology and Therapeutics, Façulty of Medicine, Porto, Portugal.
Santos
M J
MJ
Albino-Teixeira
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; D009599:Nitroprusside; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D002217:Carbachol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine