Probenecid Protects Vascular Contractile Of Thoracic Aorta In Rats Under Hypotonic Condition By Blocking Pannexin-1

Probenecid is a drug proved to act on pannexin‐1(Panx1). This study investigated the involvement of probenecid in the vascular contractile, especially when Panx1 opens under hypotonicity. We first showed the expression of Panx1 on the aortic smooth muscle cell in rats via reverse transcription polymerase chain reaction (RT‐PCR) and immunohistochemistry (Fig. 1). Then the effect of hypotonic condition (201mOsm/L) on vascular contractile of male Sprague‐Dawley rat thoracic aorta with endothelia denuded was measured, with or without adding probenecid. Finally, after incubated in the hypotonic solution with or without probenecid, the efflux adenosine triphosphate (ATP) of smooth muscle was measured. We found that under hypotonic condition, vascular contractile was greatly impaired, while probenecid markedly protected contractility of vascular smooth muscle in hypotonic stress (Fig. 2, * p <0.05, ** p <0.01). And the protection is positively related to concentration of probenecid (Fig. 3, ** p <0.01). Measurement of ATP release showed great increase when aortic rings incubating in hypotonic solution for 15 minutes (Fig. 4, * p <0.05), which was eliminated if probenecid was added in the solution with concentration of 1mM. These results indicated that probenecid protected the vascular contractile, probably via inhibiting Panx‐1 and blocking the efflux of intracellular ATP. This work was supported by grants from the Department of Science and Technology of Zhejiang Province, China (2011C23105).