VASODILATOR EFFECTS OF ADRENOMEDULLIN ON SMALL PULMONARY-ARTERIES ANDVEINS IN ANESTHETIZED CATS

1 This study was conducted to determine adrenomedullin (AM) action sit es in the pulmonary vascular bed and the relation between its vasodila tor effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmo nary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 mu m i.d.) by use of an X-ray television system on the in v ivo cat lung. 2 Under control (resting vascular tone) conditions, AM i njections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 mu m arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.0 1, 0.1, and 1 nmol kg(-1) AM, respectively) was significantly larger t han that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg(-1) AM, respectively) whatever the injected dose of AM. 3 When unilobar hypoxia (5% O-2) had decreased the i.d. of the 100-110 0 mu m arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM ( 0.1 nmol kg(-1)) was able to induce significantly larger i.d. increase s in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under c ontrol conditions. 4 The AM-induced i.d. response pattern in the seria lly connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 mu m) than in larger vessels (500-1100 mu m). In the case of CGRP, a grea ter increase was observed in the larger vessels. 5 CGRP(8-37) (100 nmo l kg(-1), i.v., followed by a continuous infusion of 0.2 nmol kg(-1) m in(-1)) had no significant effect on the i.d. Increase induced by AM ( 0.1 nmol kg(-1)) in any serial segments of the arteries and veins. 6 T he results indicate that, in the cat, AM induces greater vasodilatatio n in small pulmonary arteries and lesser vasodilatation in small veins , the maximum dilatation being in the more peripheral arterial segment (100-500 mu m). The vasodilator effect of AM was enhanced when vascul ar tone was elevated. The data suggest that the AM-induced pulmonary v asodilatation is not mediated by CGRP receptors but by its own specifi c receptor.