0166: Changes in resistance arteries expression of extracellular nucleotides signaling partners during arterial hypertension

Cardiovascular diseases are the leading cause of mortality in industrialized countries and their prevalence increases with aging populations. Small arteries constitute the main site of peripheral vascular resistance and play a key role in the regulation of blood pressure. Vascular tone is exacerbated in hypertension (HBP) and accompanied by a hypertrophy of the arterial wall. Although signaling by extracellular nucleotides is important in vascular homeostasis its contribution to vascular pathologies affecting small arteries remains poorly understood. We evaluated here the expression pattern of nucleotides signaling pathway in resistance arteries vs aorta in mice. Genes of interest including P2 receptors, ectonucleotidases (CD39, CD73) and hemi channels (connexins, pannexins) were investigated by quantitative RT-PCR. Their expression in resistance arteries was assessed in Angiotensin II-treated mice, spontaneously hypertensive rats (SHR) and, since HBP is related to age, in 24-month old mice. Our results showed that several genes are more expressed in aorta (P2ry2 and connexin 43) while others are expressed specifically (P2rx1, connexin 37) or preferentially (P2ry6) in small arteries. The latest might be involved in pathologies affecting the small arteries. With HBP, we observed a decreased connexin 37 and 40 expression level in Angiotensin II-treated mice and in SHR respectively and both decreased with aging. Interestingly, CD39 (tone regulator) decreased in the two models of HBP and with aging. Such decrease in nucleotidase activity may enhance P2 receptors activation and increase vascular contractility/tone. This is especially true considering P2Y6 (tone promoter) that increased with aging. Further studies may allow us to evaluate the contribution of these mediators in the development of small arteries defect in aging associated or not with HBP. Signaling by extracellular nucleotides may constitute new therapeutic targets in the treatment of HBP