Effects of nine different gastrointestinal polypeptides on vascular smooth muscle in vitro

Nine polypeptides of gastrointestinal origin were tested for their possible effect on vascular smooth muscle of the rat portal vein. The substances tested were bombesin, caerulein, glucagon, insulin, pentagastrin, secretin, somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Cumulative dose-response relations of integrated mechanical activity (mean tension) were obtained with maximal concentrations of the various peptides of 1-10 microgram/ml. Within this concentration range, only substance P and VIP showed clearcut effects; substance P causing contraction and VIP relaxation. The dose of substance P needed to produce contraction was high (ED50 greater than 1 microM) so that the physiological importance of this response is doubtful. On the other hand, ED50 for the relaxing effect of VIP was about 15 nM, which is in accordance with concentrations reported to produce significant vasodilatation in vivo. The results support the view that vascular effects which have been reported to occur in response to the other 7 peptides are mainly of indirect origin and not mediated via direct action on vascular smooth muscle.