title: Repeated inhalation of adrenomedullin ameliorates pulmonary hypertension and survival in monocrotaline rats.
abstract: Adrenomedullin (AM) is a potent vasodilator peptide. We investigated whether inhalation of aerosolized AM ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Male Wistar rats given MCT (MCT rats) were assigned to receive repeated inhalation of AM (n = 8) or 0.9% saline (n = 8). AM (5 mug/kg) or saline was inhaled as an aerosol using an ultrasonic nebulizer for 30 min four times a day. After 3 wk of inhalation therapy, mean pulmonary arterial pressure and total pulmonary resistance were markedly lower in rats treated with AM than in those given saline [mean pulmonary arterial pressure: 22 +/- 2 vs. 35 +/- 1 mmHg (-37%); total pulmonary resistance: 0.048 +/- 0.004 vs. 0.104 +/- 0.006 mmHg.ml(-1).min(-1).kg(-1) (-54%), both P < 0.01]. Neither systemic arterial pressure nor heart rate was altered. Inhalation of AM significantly attenuated the increase in medial wall thickness of peripheral pulmonary arteries in MCT rats. Kaplan-Meier survival curves demonstrated that MCT rats treated with aerosolized AM had a significantly higher survival rate than those given saline (70% vs. 10% 6-wk survival, log-rank test, P < 0.01). In conclusion, repeated inhalation of AM inhibited MCT-induced pulmonary hypertension without systemic hypotension and thereby improved survival in MCT rats.
authors.affiliation: Dept. of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. nagayann@hsp.ncvc.go.jp
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okumura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Uematsu
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ono
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000280:Administration, Inhalation; D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D016686:Monocrotaline; D010455:Peptides / Q000494:pharmacology*; D011379:Prognosis; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D010455:Peptides; D053607:Adrenomedullin; D016686:Monocrotaline