Contractile Changes in the Vasculature After Subchronic Smoking: A Comparison Between Wild Type and Surfactant Protein D Knock-Out Mice.
BACKGROUND
Cigarette smoking is a well-known risk factor for developing cardiovascular diseases, but the underlying mechanisms are largely unknown. Recent data suggest that vasocontractile receptor modulation could be an important factor. Surfactant protein D (SP-D) is important in the particle clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup.


METHODS
Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were obtained.


RESULTS
CSE caused a leftward shift in the concentration response curves for endothelin-1 in the BA for both WT and SP-D KO. UDP, acting on the purinergic P2Y6 receptor, caused reduced contraction in the left descending artery and increased contraction in the BA in the CSE WT mice. SP-D KO mice displayed no smoke induced changes, but were surprisingly similar to the CSE WT.


CONCLUSIONS
The contractility to UDP was altered in the brain and heart vasculature of CSE mice. SP-D KO (both control and CSE) and CSE WT had similar changes in contractility compared to control WT.


CONCLUSIONS
These results show that sub-chronic smoking induces vascular changes in the WT, mainly for the purinergic P2Y6 receptor together with minor changes for the endothelin-1 receptor. SP-D KO (both control and CSE) does not show any further changes compared to CSE WT.
Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark; kristian.agmund.haanes@regionh.dk.
Kristian Agmund
KA
Haanes
Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark;
Lars Schack
LS
Kruse
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Helle
H
Wulf-Johansson
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Christian Christensen
CC
Stottrup
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Grith Lykke
GL
Sorensen
Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark;
Lars
L
Edvinsson
D000818:Animals; D008168:Lung / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009213:Myography; D011656:Pulmonary Emphysema / Q000209:etiology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D012907:Smoking / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology*
D037663:Pulmonary Surfactant-Associated Protein D; D044022:Receptor, Endothelin A; D058470:Receptors, Purinergic P2Y