Abstract P268: Extracellular Vesicles from Wistar Kyoto and Spontaneously Hypertensive Rats Have Differential Vasodilatory Effects on Resistance Arteries

Abstract

Extracellular vesicles (EVs) have been described as novel bio-markers and bio-activators in vascular dysfunction in HTN. However, the exact mechanism how EVs affect vascular function is not known. We hypothesized that hypertensive and normotensive EVs have differential vasodilatory effects on resistance arteries. To examine the effects of EVs on acetylcholine (ACh)-mediated vasodilation, we freshly isolated 3 rd /4 th order mesenteric arteries and circulating EVs from 6 and 12-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Arteries were cannulated on a pressure myograph and pressurized to 80 mmHg. EVs (~6x10 7 EV/mL) from hypertensive and normotensive 6 and 12 week old rats were added to the vessel lumen and circulating bath solutions and equilibrated for 10 min. We also added EVs after delipidation with Chloroformmethanol. Inner diameter was measured as cumulative concentrations of ACh were applied to the bath following a preconstruction with 10 μM phenylephrine (PE). No significant difference in ACh vasodilation was observed in arteries from WKY and SHR rats, although SHR arteries were more vasoconstrictive to PE. Interestingly, EVs from WKY had an anti-vasodilatory effect on WKY arteries, whereas EVs from SHR had no effect compared to control condition without EVs. This differential effect was not observed in arteries from SHR rats treated with WKY or SHR EVs. The anti-vasodilatory effect on WKY arteries was also achieved by infusing either delipidated EVs from 12 week-old SHR, or intact EVs from 6 week old SHR rats that have not yet developed hypertension. Together, these data suggest that EVs from normotensive WKY rats and pre-hypertensive SHR rats have anti-vasodilatory effects on healthy resistance arteries. Additionally, the anti-vasodilatory effect of pre-hypertensive SHR EVs is dependent on intact vesicles, but not that of WKY EVs. The effect of normotension on EV cargo might be more important to vasodilatory response than EV species source. This data supports the functional role of EVs in vascular regulation in HTN. Further studies are needed to delineate the effector cargo of these functional EVs.