Inhibition of neurogenic vasodilation and plasma extravasation by substance P antagonists, somatostatin and [D-Met2, Pro5]enkephalinamide.

The substance P (SP) analogues [D-Pro2, D-Phe7, D-Trp9]SP and [D-Pro2, D-Trp7,9]SP, which have been reported to be SP antagonists, inhibited the vasodilation and plasma extravasation induced by antidromic stimulation of the saphenous nerve or by i.a. infusion of SP. Somatostatin inhibited the vasodilatation and plasma extravasation induced by saphenous nerve stimulation, but had no effect on the vascular responses to i.a. infused SP. The opiate agonist [D-Met2, Pro5]enkephalinamide inhibited the vasodilation evoked by antidromic nerve stimulation in a naloxone reversible manner, but did not change the effect of i.a. infusion of SP. Calcitonin and caerulein had no effect on neurogenic vasodilatation. These results further support the concepts that neurogenic vasodilatation and plasma extravasation are mediated by SP, and that somatostatin and opiates inhibit the release of SP from peripheral sensory nerve endings.