Pulmonary vasodilator response to adrenomedullin in patients with pulmonary hypertension.
This study sought to investigate pulmonary vasodilator responses to intrapulmonary and intravenous infusion of adrenomedullin (AM) in patients with pulmonary hypertension. In 10 patients with pulmonary hypertension, blood flow velocity in a segmental pulmonary artery was measured using a Doppler flow wire during intrapulmonary infusion of AM, acetylcholine (ACh), and adenosine triphosphate (ATP). The hemodynamic effects of intravenously administered AM (0.05 microg/kg/min) were examined in another 5 patients with primary pulmonary hypertension. Intrapulmonary infusion of AM, ACh or ATP caused a significant dose-dependent increase in blood flow velocity in a segmental pulmonary artery, respectively. The increase in flow velocity with AM at 10(-8) mol/l (41 +/- 6% of the baseline value) was comparable to that with ACh at 10(-4) mol/l (39 +/- 11%) and that with ATP at 10(-5) mol/l (36 +/- 14%), suggesting a strong pulmonary vasodilator activity of AM. Intravenous infusion of AM produced a 41% increase in cardiac index (p < 0.05) and a 30% decrease in pulmonary vascular resistance (p < 0.05) with a 3% reduction in mean pulmonary arterial pressure (p = NS). These results suggest that, on a molar basis, AM may have much more potent pulmonary vasodilator activity than ACh and ATP, and thus may have beneficial hemodynamic effects in patients with pulmonary hypertension.
Nagaya
Noritoshi
N
Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565, Japan. nagayann@hsp.ncvc.go.jp
Miyatake
Kunio
K
Kyotani
Shingo
S
Nishikimi
Toshio
T
Nakanishi
Norifumi
N
Kangawa
Kenji
K
D000109:Acetylcholine / Q000008:administration & dosage; D000293:Adolescent; D053607:Adrenomedullin; D000328:Adult; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007275:Injections, Intravenous; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000109:Acetylcholine