VASCULAR MODULATION FOR NUCLEOTIDE RECEPTORS (P2Y) AFTER TLR4 ACTIVATION

BARBEIRO H. V.(1), BARBEIRO D. F.(1), GUIDO M. C.(1), SORIANO F. G.(1)

(1)Emergências Clínicas - LIM 51, FMUSP, São Paulo, SP, Brasil.

Abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of a lot of diseases. Thus, the purpose of this study is to evaluate the modulation by ATP in the vascular reactivity and the superoxide quantification in isolated rats aorta after LPS injection. LPS (10mg/kg i.p.) was injected in Wistar rats 8h and 16h before the experiment, the control group received saline solution and were anesthetized with chloral hydrate 10% i.p.  The average arterial pressure (femoral) was evaluated. For the quantification of mRNA and nitrate, aortas had been homogenized in liquid nitrogen.  In the study of vascular reactivity in vitro and for O2- we used thoracic aorta clean and unbroken. Statistical analysis was made by ANOVA.  The MAP (Mean Arterial Pressure) reduced in 8h and 16h.  mRNA for iNOS and TLR4 increased in 8h; no difference was observed in 16h. Nitrate and O2- increased in 16h, ATP presence reduced O2- in 16h. This reduction is predominantly for P2Y receptors; therefore in the presence of P2Y antagonist (Reactive Blue) the ATP practically does not reduced this quantification. In the presence of P2X antagonist (PPADS) the reduction was of 34,57%.  It was observed, in the vascular reactivity, difference in the maximum relaxation to ATP when we compare 16h with control. Purinergic substances reduce O2- in septic aorta, mainly via P2Y receptors. This action may modulate (in vivo) O2-, indirectly NO, iNOS and also arterial pressure.

KEY WORDS: Vascular reactivity, Superoxide

FINANCIAL SUPPORT:  FAPESP, FFM, HCFMUSP

CORRESPONDENCE TO:

Hermes Vieira Barbeiro, LIM 51, Faculdade de Medicina, Universidade de São Paulo - USP, CEP 01246-903, São Paulo, SP. Email: barbeiro@emercli.fm.usp.br