EFFECTS OF AGE AND INDOMETHACIN ON RESPONSE AND SENSITIVITY OF PULMONARY-ARTERY TO PHENYLEPHRINE AND TO HISTAMINE IN PIGS

The vasoconstrictor effects of phenylephrine and histamine were invest igated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels wit h indomethacin. Potency (pD2 values) and maximal effects (E(max)) reco rded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 /- 0.17 and 0.76 +/- 0.22 g/mg of dry tissue respectively (mean +/- SE M)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 +/- 0.30 and 1.06 +/- 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were sig nificantly reduced in 26-week-old mature pigs (group 3, n = 6) as indi cated by the decrease in pD2 (3.91 +/- 0.23; P < 0.01) and E(max) (0.2 7 +/- 0.13 g/mg of dry tissue; P < 0.05) values observed in this group . Histamine (10(-3)M)-induced maximal responses (E(max)) were signific antly higher in group 2 (2.23 +/- 0.49 g/mg) than in group 1 (0.85 +/- 0.11 g/mg; P < 0.05) and in group 3 (0.48 +/- 0.10 g/mg; P < 0.01). I n 5-week-old animals, indomethacin (3.10(-5)M) Significantly (P < 0.05 ) shifted the concentration-response curve to phenylephrine to the rig ht (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% (P < 0.05) in E(max) This cyclo-o xygenase inhibitor had no effect in other groups. These data indicate that phenylephrine is a potent and effective vasoconstrictor agent for the main pulmonary arteries in 5-week-old piglets and that alpha-1-ad renergic-induced contractions are enhanced by cyclo-oxygenase products . These findings can be related with the high reactivity of pulmonary vascular smooth muscles in these animals.