To test the potential for vasoactive neuropeptide receptors to affect capillary resistance, we have begun to study the plausibility that pericytes might be equipped to respond to a representative peptide vasoconstrictor and a representative peptide vasodilator. Pericytes cultured from the bovine retinal vasculature specifically bind the angiotensin II (Ang II) antagonist saralasin (1 nM125I-saralasin bound at 2.2 ± 0.41 fmol/mg protein) and 125I-vasoactive intestinal peptide (VIP; Kd of 0.5 nM with a population of 30 fmol/mg protein). Incubation with 100 µM Ang II induced minimal cAMP synthesis, while VIP (1 µM, 10 µM) did not induce any change in cAMP concentration. Ang II (10 µM and 100 µM) caused contraction of pericytes cultured on an elastic silicone surface. Circulating or locally produced vasoactive neuropeptides might affect pericyte contractile tone via several intracellular pathways, moderated by indirect effects of these peptides through endothelial stimulation, with the net effect on local blood flow resulting from the effects on arteries and veins as well as capillaries.