Regulation of Vascular Tone in Resistance and Conduit Vessels of Trained Rats: Effects of 20-HETE

PURPOSE: Regular physical activity induces a range of adaptations that modulate vascular tone. Although the roles of several mediators in exercise-induced vascular changes have been established, the effect of the vasoconstrictive 20-hydroxyeicosatetraenoic acid (20-HETE) has not been examined. We investigated the effect of 20-HETE on vascular tone in resistance and conduit arteries after exercise training and its potential impact on systemic blood pressure. METHODS: Wistar rats were assigned to control or exercise (swimming, 1h/day, 5days week, 8-weeks) groups. Mean arterial pressure (MAP) was measured before and after acute inhibition of 20-HETE synthesis with HET0016. In thoracic aorta and gastrocnemius resistance arteries, the direct effect of 20-HETE and its modulation of responses to phenylephrine, vasopressin, and angiotensin II were assessed using organ bath and wire myograph. Vascular 20-HETE and CYP4A expression were quantified by ELISA and Western blot. RESULTS: Baseline MAP was similar between groups, but the fall in pressure produced by acute 20-HETE synthesis inhibition was significantly attenuated in trained rats. In gastrocnemius resistance arteries, blockade of endogenous 20-HETE produced a vasodilation that was markedly reduced by exercise, whereas the thoracic aorta response was unchanged. Endogenous 20-HETE contributed to vasopressin and angiotensin II induced contraction in both vessel types; in resistance arteries this contribution's dependence on training was clearest for vasopressin. CYP4A expression and 20-HETE content were significantly reduced in gastrocnemius resistance vessels of trained rats. CONCLUSIONS: This is the first study to demonstrate that regular swimming exercise reduces the contribution of 20-HETE to vascular tone and MAP, most prominently in skeletal muscle resistance arteries, through downregulation of vascular CYP4A expression and 20-HETE production.