2,2′‐Nitrophenylisatogen potentiates P2X1 receptor mediated vascular contraction and blood pressure elevation

Abstract

AbstractThe objective of this research was to examine the effects of chemical compounds with possible P2 receptor modulating effects and to characterize the potentiating effects of 2,2′‐nitrophenylisatogen (NPI) on P2X1 receptors in vitro and in vivo. Chemical compounds were tested in an in vitro pharmacological assay using vascular segments from the rat mesenteric artery stimulated by P2 receptor‐specific agonists. Contractions were expressed as a percentage of 60 mM K+‐induced contractions. Blood pressure was evaluated in pithed rats. NPI (30 μM) added 15 min before addition of the P2X1 receptor‐specific agonist αβ‐MeATP increased the maximum vasoconstriction from 23% to 49% (an increase of 113%). Furthermore, NPI prevented the desensitization of repeated αβ‐MeATP contractions. Related compounds were examined, and 2‐(3‐methoxy‐phenyl)‐1‐oxy‐indol‐3‐one (MPI) had similar effects as NPI, but several others lacked effect. NPI had no effect on ADPβS (P2Y1) or acetylcholine‐mediated vasodilatation, nor on UTP (P2Y2/4), UDP (P2Y6), or noradrenaline‐mediated contractions. In pithed rats, the blood pressure response to 50 nmol/kg‐infusion of αβ‐MeATP was increased from 50±6 to 63±5 mmHg (P<0.05), but had no effect on basal blood pressure or on the cardiovascular response to preganglionic nerve stimulation. In conclusion, NPI and MPI potentiates P2X1 receptor vascular contractions in vitro and (NPI) blood pressure effects in vivo. It is possible that the effect is mediated by an inhibition of P2X1 receptor desensitization. Drug Dev. Res. 59:82–87, 2003. © 2003 Wiley‐Liss, Inc.