Evidence for specific regional patterns of responses to different vasoconstrictors and vasodilators in sheep isolated pulmonary arteries and veins.

1. Responses of large (5-7 mm in diameter) and medium sized (3-4 mm in diameter) branches of sheep isolated intrapulmonary arteries and veins and three groups of small pulmonary arteries (200, 500 and 1000 microns diameter) to the vasoconstrictors endothelin-1, 5-hydroxytryptamine (5-HT), noradrenaline and the thromboxane A2 mimetic, U46619, were examined. Also, relaxation responses to the endothelium-dependent vasodilators, acetylcholine (ACh), bradykinin and ionomycin and the endothelium-independent vasodilator, sodium nitroprusside (SNP), were studied to determine their predominant site of action within the pulmonary vasculature. 2. Endothelin-1 was the most potent vasoconstrictor tested in all vessels. The maximum response to endothelin-1, expressed as a percentage of the maximum contraction to KC1 depolarization, did not differ significantly between the different vessels. By contrast, pulmonary arteries greater than 200 microns in diameter failed to contract to U46619, whereas U46619 was a potent constrictor of large and medium-sized veins. 3. 5-HT caused similar contractions in all arteries > 200 microns in diameter, but the maximum response was significantly diminished in smaller arteries. By contrast, the maximum response to noradrenaline was progressively attenuated with decreasing arterial diameter. Both 5-HT and noradrenaline caused poor contractions in veins. Pulmonary veins were less sensitive to 5-HT than arteries and at low concentrations 5-HT caused relaxation. No change in sensitivity to noradrenaline was noted between the arteries and veins. 4. Relaxation responses to bradykinin and ionomycin decreased progressively along the pulmonary vascular tree and were nearly absent in large veins. Also, ACh was a poor relaxing agent of large and medium-sized arteries and failed to mediate any relaxation response in other vessel segments. Surprisingly the smallest arteries examined (approximately 200 microns in diameter) failed to relax to ionomycin, bradykinin and SNP. However, both the sensitivity and maximum relaxation to SNP were similar in all other arterial and venous segments. 5. In conclusion, marked regional differences in reactivity to both vasoconstrictors and vasodilators occur in arterial and venous segments of the sheep isolated pulmonary vasculature. Such specialization may have important implications for the regulation of resistance in this low tone vascular bed.