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.