Abstract
Cigarette smoke (CS) and chronic hypoxia (CH) can produce pulmonary hypertension. Similarities and differences between both exposures and their interaction have not been explored.
Investigate the effects of CS and CH, as single factors or in combination, on the pulmonary circulation in the guinea pig.
Fifty-one guinea pigs were exposed 12 weeks to CS, and 32 sham-exposed. 50% of the animals in each group were additionally exposed to hypoxia the last 2 weeks. We measured pulmonary artery pressure (PAP) and the weight ratio between right ventricle (RV) and left ventricle+septum. Pulmonary artery contractility in response to norepinephrine (NE), endothelium-dependent vasodilatation and distensibility were evaluated in organ bath chambers. The number of small intrapulmonary vessels showing immunoreactivity to smooth muscle (SM)-α-actin and double elastic laminas was assessed microscopically.
CS and CH induced similar increases of PAP and RV hypertrophy (p<0.05, each), effects that were further enhanced when both factors were combined. CH increased the contractility to NE (p<0.01) and reduced the distensibility (p<0.05) of pulmonary arteries. Animals exposed to CS showed an increased number of small vessels with positive immunoreactivity to SM-α-actin (p<0.01) and those exposed to CH a greater proportion of vessels with double elastic laminas (p<0.05).
We conclude that chronic hypoxia amplifies the detrimental effects of CS on the pulmonary circulation by altering the mechanical properties of pulmonary arteries and enhancing the remodeling of pulmonary arterioles.
- ERS