Pulmonary hypertension induced in rats by monocrotaline and chronic hypoxia is reduced by p-chlorophenylalanine.
We have studied the role of 5-hydroxytryptamine (5-HT) in monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats using p-chlorophenylalanine (PCPA) which inhibits 5-HT synthesis. We measured right ventricular mean systolic pressure (Prvs), right ventricular hypertrophy, medial thickness of muscular pulmonary arteries, and muscularization of pulmonary arterioles 17 days after a single dose of monocrotaline (60 mg/kg) and after 26 days of chronic hypobaric hypoxia (380 mm Hg). In monocrotaline pulmonary hypertension, pretreatment with PCPA (500 mg/kg) was associated with significant reductions (p less than 0.05) in Prvs (29%), right ventricular hypertrophy (33%), and medial thickness of muscular pulmonary arteries (14%). In chronic hypoxic pulmonary hypertension, pretreatment with PCPA was associated with significant reductions in Prvs (20%), right ventricular hypertrophy (28%), medial thickness of muscular pulmonary arteries (14%), and muscularization of pulmonary arterioles (47%). 5-HT may play a role in the development of monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats.
Kay
J M
JM
Keane
P M
PM
Suyama
K L
KL
D000818:Animals; D002908:Chronic Disease; D005260:Female; D010134:Fenclonine / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D011763:Pyrrolizidine Alkaloids; D012701:Serotonin; D016686:Monocrotaline; D010134:Fenclonine