Dissociation of chronic vascular cell proliferation and vascular contractility after chronic cigarette smoke exposure.
In guinea pigs, chronic cigarette smoke exposure produces physiological and structural alterations in the pulmonary vasculature via unknown mechanisms. This study aimed to determine whether chronic cigarette smoke exposure can induce altered pulmonary vascular reactivity, and whether chronic smoke exposure would be associated with a continued increase in vascular cell deoxyribonucleic acid (DNA) synthesis, indicative of cell proliferation. Guinea-pigs were therefore exposed to two regimens of smoke. In the first experiment, animals were exposed once to the smoke of seven cigarettes, and sacrificed 24 h post-smoke, while in the second experiment, the guinea-pigs were exposed for 5 days each week for 4 months. Control animals were exposed to air. Lung explant preparations and computer linked image photography were utilized to determine vascular reactivity, and DNA synthesis was assessed using the 5-bromo-2'-deoxyuridine technique. Neither acute nor chronic smoke exposure affected vascular reactivity, although the older animals had lesser reactivity. In the chronically smoked animals, evidence was found of ongoing vascular DNA synthesis, and evidence of structural alterations with increased muscularization of the arterioles (34.7+/-7.6% of arterioles in control versus 62.7+/-5.5% after smoke exposure). Despite evidence of continued deoxyribonucleic acid synthesis in the peribronchiolar vessels, the alterations of vascular physiology previously found in this model cannot be ascribed to increased reactivity at this site. Instead, the chronic deoxyribonucleic acid synthesis in the arterioles adjacent to the alveolar ducts, culminating in an increased number of fully muscularized vessels, would suggest this compartment as the most probable source.
Wright
J L
JL
Dept of Pathology, University of British Columbia, Canada.
Sun
J P
JP
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010947:Plants, Toxic; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D012906:Smoke; D014026:Nicotiana; D014661:Vasoconstriction / Q000502:physiology*
D012906:Smoke; D004247:DNA; D001973:Bromodeoxyuridine