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 mu m diameter) to the vasoconstrictors endothelin-1, 5-hydroxytryptamine (5 -HT), noradrenaline and the thromboxane A(2) mimetic, U46619, were exa mined. Also, relaxation responses to the endothelium-dependent vasodil ators, acetylcholine (ACh), bradykinin and ionomycin and the endotheli um-independent vasodilator, sodium nitroprusside (SNP), were studied t o determine their predominant site of action within the pulmonary vasc ulature. 2 Endothelin-1 was the most potent vasoconstrictor tested in all vessels. The maximum response to endothelin-1, expressed as a perc entage of the maximum contraction to KCl depolarization, did not diffe r significantly between the different vessels. By contrast, pulmonary arteries greater than 200 mu m in diameter failed to contract to U4661 9, whereas U46619 was a potent constrictor of large and medium-sized v eins. 3 5-HT caused similar contractions in all arteries >200 mu m in diameter, but the maximum response was significantly diminished in sma ller 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 w ere less sensitive to 5-HT than arteries and at low concentrations 5-H T caused relaxation. No change in sensitivity to noradrenaline was not ed between the arteries and veins. 4 Relaxation responses to bradykini n and ionomycin decreased progressively along the pulmonary vascular t ree and were nearly absent in large veins. Also, ACh was a poor relaxi ng agent of large and medium-sized arteries and failed to mediate any relaxation response in other vessel segments. Surprisingly the smalles t arteries examined (similar to 200 mu m in diameter) failed to relax to ionomycin, bradykinin and SNP. However, both the sensitivity and ma ximum relaxation to SNP were similar in all other arterial and venous segments. 5 In conclusion, marked regional differences in reactivity t o both vasoconstrictors and vasodilators occur in arterial and venous segments of the sheep isolated pulmonary vasculature. Such specializat ion may have important implications for the regulation of resistance i n this low tone vascular bed.