Endothelin-1 inhibits the vasodilation induced by substance P in isolated porcine ophthalmic artery.

The vasoconstrictor effect of endothelin-1 is long-lasting and slow in onset, suggesting that this peptide may be involved with long-term vascular responses. Substance P, a quick-acting, vasodilatory tachykinin present in sensory nerves, may be released by trigeminal fibres and thereby participate in the regulation of vascular tone in the head. Given the potential role of vasoregulatory peptides in the ocular-forehead circulation in the pathophysiology of vascular headaches, the interactions between substance P and endothelin-1 over time were studied in isolated porcine ophthalmic artery. Substance P-induced relaxation of precontracted artery segments was significantly diminished by endothelin-1, despite the fact that endothelin-1 itself had no further significant contractile effect on these arteries. It is also noteworthy that the observed reduction of substance P-induced relaxation occurred much more rapidly than the onset of endothelin-1-induced contraction in relaxed porcine ophthalmic artery. The results suggest an inhibitory synergism between endothelin-1 and substance P in this vascular bed.