endothelin alters the reactivity of vasa vasorum mechanisms and implications for conduit vessel physiology and pathophysiology 1 the walls of certain large blood vessels are nourished by the vasa vasorum a network of microvessels that penetrate the adventitia and media of the vessel wall the purpose of this study was to characterize endothelin1 et1mediated contraction of vasa and to investigate whether threshold concentrations of et1 alters the sensitivity to constrictors arterial vasa were dissected from the walls of porcine thoracic aorta and mounted in a tension myograph 2 et1 and etbselective agonist sarafotoxin 6c s6c produced concentrationdependent contraction eta receptor antagonist bq123 10 microm caused a biphasic rightward shift of et1 response curves etb receptor antagonist bq788 1 microm produced a rightward shift of response curves to et1 and s6c of 5 and 80 fold respectively 3 et1 responses were abolished in ca2free pss but unaffected by selective depletion of intracellular ca2 stores nifedipine 10 microm an ltype ca2 channel blocker attenuated et1 responses by 44 inhibition of receptoroperated ca2 channels or nonselective cation entry using skf 96365 30 microm and ni2 1 mm respectively attenuated et1 contractions by 60 4 et1 13 nm enhanced responses to noradrenaline na 4 fold but not to thromboxane a2mimetic whilst k 1020 mm sensitized vasa to both types of constrictor 5 therefore et1induced contraction of isolated vasa is mediated by eta and etb receptors and involves ca2 influx through ltype and nonltype ca2 channels furthermore elevation of basal tone of vasa vasorum alters the profile of contractile reactivity these results suggest that et1 may be an important regulator of vasa vasorum reactivity