A comparison of the differential effects of vasoactive intestinal peptide and peptide histidine isoleucine on the vascular and capsular smooth muscle of the dog spleen.

1. The actions of the two peptides, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been compared to that of isoprenaline on the smooth muscle systems of the isolated blood-perfused dog spleen. 2. Intra-arterial injections of VIP and PHI caused graded increases in splenic arterial blood flow at constant perfusion pressure indicative of splenic arterial vasodilatation. 3. VIP was significantly more potent than PHI, with their respective molar ED50 values being 9.9 +/- 3.7 and 830 +/- 141 pmol (P less than 0.002). VIP was approximately 10 and 200 times more potent than isoprenaline and PHI respectively. 4. The maximum reduction in splenic arterial vascular resistance was the same (P greater than 0.5) in response to intra-arterial VIP and PHI, although both peptide maxima were significantly less (P less than 0.05, 0.01 respectively) than that obtained with isoprenaline. 5. Small increases in spleen volume accompanied the splenic vasodilator responses to both peptides. They were probably passive in origin, secondary to splenic arterial vasodilatation. 6. The selective beta 2-adrenoceptor antagonist, ICI 118,551, did not antagonize the splenic arterial vasodilator response to VIP or PHI but markedly attenuated the effect of isoprenaline. 7. These observations indicate that VIP and PHI, when either co-released locally or present together in the systemic circulation, may exert a differential action on different components of the circulation.