Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens right ventricular hypertrophy in rats administered monocrotaline.
A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid (mRNA), and the mRNA for its receptor are highly expressed in the lung, suggesting that adrenomedullin may play a role in the regulation of the pulmonary circulation. We investigated whether the chronic infusion of rat adrenomedullin would affect pulmonary hypertension and right ventricular hypertrophy produced by the administration of monocrotaline. Four-week-old male Wistar rats received a single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma levels of adrenomedullin were significantly higher in the PH vs. the control group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension increased the plasma levels of adrenomedullin to a value 94% greater than that of the control group and 55% greater than that of the untreated PH group. Chronic infusion of adrenomedullin significantly lessened the increase in right ventricular systolic pressure and the ratio of right ventricular weight to body weight seen after monocrotaline treatment. Histological examination revealed that adrenomedullin also attenuated the medial thickening of the pulmonary artery. These results suggest that chronic infusion of adrenomedullin attenuates the pulmonary hypertension and right ventricular hypertrophy seen in rats treated with monocrotaline.
Yoshihara
F
F
Research Institute, National Cardiovascular Center, Suita, Osaka, Japan.
Nishikimi
T
T
Horio
T
T
Yutani
C
C
Takishita
S
S
Matsuo
H
H
Ohe
T
T
Kangawa
K
K
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D015918:Infusion Pumps, Implantable; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D010455:Peptides; D053607:Adrenomedullin; D016686:Monocrotaline