Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology

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 endothelin‐1 (ET‐1)‐mediated contraction of vasa and to investigate whether threshold concentrations of ET‐1 alters the sensitivity to constrictors. Arterial vasa were dissected from the walls of porcine thoracic aorta and mounted in a tension myograph. ET‐1 and ET B ‐selective agonist, sarafotoxin 6c (S6c), produced concentration‐dependent contraction. ET A receptor antagonist, BQ123 (10 μ M ), caused a biphasic rightward shift of ET‐1 response curves. ET B receptor antagonist, BQ788 (1 μ M ), produced a rightward shift of response curves to ET‐1 and S6c of 5‐ and 80 fold respectively. ET‐1 responses were abolished in Ca 2+ ‐free PSS but unaffected by selective depletion of intracellular Ca 2+ stores. Nifedipine (10 μ M ), an L‐type Ca 2+ channel blocker, attenuated ET‐1 responses by 44%. Inhibition of receptor‐operated Ca 2+ channels or non‐selective cation entry using SKF 96365 (30 μ M ) and Ni 2+ (1 m M ) respectively, attenuated ET‐1 contractions by 60%. ET‐1 (1–3 n M ) enhanced responses to noradrenaline (NA) (4 fold) but not to thromboxane A 2 ‐mimetic, whilst K + (10–20 m M ) sensitized vasa to both types of constrictor. Therefore, ET‐1‐induced contraction of isolated vasa is mediated by ET A and ET B receptors and involves Ca 2+ influx through L‐type and non‐L‐type Ca 2+ channels. Furthermore elevation of basal tone of vasa vasorum alters the profile of contractile reactivity. These results suggest that ET‐1 may be an important regulator of vasa vasorum reactivity.British Journal of Pharmacology (1999) 128 , 1229–1234; doi: 10.1038/sj.bjp.0702930