Characterization of the relaxant effects of vasoactive intestinal peptide (VIP) and PHI on isolated brain arteries.

We have studied the vasorelaxant properties of vasoactive intestinal peptide (VIP) using helical strips of bovine, porcine and human brain arteries in vitro. The resting tension of the arterial strips was increased during experiments by prostaglandin F2 alpha or KCl so as to increase the magnitude of the relaxant response to VIP. Arteries supplying different regions of the bovine brain responded potently to VIP with ED50 values of 1.8 nM, 2.3 nM, 6.8 nM and 9.0 nM for the middle, anterior and posterior cerebral arteries and the basilar artery, respectively. The porcine basilar artery and branches of the human middle cerebral artery responded to VIP with ED50 values of 4.2 nM and 1.6 nM, respectively. The homologous neuropeptide, PHI, relaxed the bovine middle cerebral and porcine basilar arteries less potently than did VIP, with ED50 values for PHI being 11 nM and 43 nM, respectively. However, PHI elicited in the two arteries a maximal vasodilatory response of similar magnitude as did VIP. The other homologous peptides, human pancreatic growth hormone releasing factor 1-40 [hpGRF 1-40], secretin, and glucagon, and the VIP fragments, VIP 1-12 and VIP 10-28, were completely inactive. In contrast, VIP, which had been oxidized to VIP-(Met17 sulfoxide) or VIP-(Met17 sulfone), retained full activity. These structure-activity relationships for relaxation of brain arteries are consistent with previous studies of other biological responses to VIP.