Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats.
1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cai
Y N
YN
University Department of Medicine, Royal Hallamshire Hospital, Sheffield, U.K.
Barer
G R
GR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000150:complications*; D011651:Pulmonary Artery / Q000503:physiopathology; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000627:therapeutic use*
D011719:Pyrazines; D014665:Vasodilator Agents; C017953:tetramethylpyrazine