Evidence that hypoxic pulmonary vascular remodeling in rats is polyamine dependent

Area of Science:

• Physiology
• Biochemistry

Background:

• Polyamines are low-molecular-weight organic cations involved in cell growth and differentiation.
• Chronic hypoxia is known to cause pulmonary vascular remodeling.

Purpose of the Study:

• To investigate if polyamines mediate chronic hypoxia-induced pulmonary vascular remodeling.
• To determine the effect of inhibiting polyamine synthesis on hypoxia-induced changes.

Main Methods:

• Animals were exposed to chronic hypoxia (inspired O2 fraction = 0.1 for 21 days).
• Pulmonary arterial pressures, medial thickness, hematocrits, and right ventricular hypertrophy were measured.
• Lung polyamine content was analyzed.
• alpha-Difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, was administered.

Main Results:

• Chronic hypoxia increased pulmonary arterial pressure, medial thickness, hematocrit, and right ventricular hypertrophy.
• Hypoxic animals showed higher lung polyamine levels (putrescine, spermidine, spermine).
• DFMO attenuated hypoxia-induced increases in lung putrescine and spermidine, and blunted pulmonary arterial pressure and medial thickness elevations.
• DFMO did not affect hematocrit or right ventricular hypertrophy and did not alter responses to acute hypoxia.

Conclusions:

• Polyamines are mediators of chronic hypoxia-induced pulmonary vascular remodeling.
• Inhibiting polyamine synthesis with DFMO attenuates sustained pulmonary arterial pressure increase by reducing hypoxia-induced medial thickening.