Pulmonary vascular effects of vasoactive intestinal peptide in conscious newborn lambs

Vasoactive intestinal peptide (VIP) may be a neurotransmitter in a peptidergic nervous system and is found in nerves in pulmonary blood vessels. Information regarding its pulmonary vascular effects is limited. We therefore studied VIP's effect on pulmonary vascular tone in the immature lung. Normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around the right and left pulmonary arteries were used. VIP was injected into one pulmonary artery only, and direct effects of this peptide on the pulmonary vessels were determined by comparing the flow changes in the injected vs. the uninjected lung. VIP was a powerful pulmonary vasodilator with a threshold of 0.3 microgram/kg. It also was a systemic vasodilator (after 1 microgram/kg, aortic pressure fell 27% and cardiac output increased 29%, both P less than 0.01), with a threshold of 0.1 microgram/kg. Pretreatment with propranolol (1 mg/kg iv) did not abolish pulmonary or systemic vasodilation after VIP. On the other hand, pretreatment with indomethacin (3 mg/kg per day for 3 days) abolished VIP-induced pulmonary vasodilation but probably did not affect systemic vasodilation. We conclude that VIP is a powerful pulmonary vasodilator in the newborn lamb and that this dilation can be blocked by the cyclooxygenase inhibitor indomethacin. VIP is also a powerful systemic vasodilator in the newborn lamb but this effect is not blocked by either propranolol or indomethacin.