Chronic cigarette smoke exposure causes hypertension, leukocyte‐specific reactive oxygen species (ROS) generation, endothelial dysfunction, and cardiac hypertrophy in mice

Cigarette smoking is a major risk factor for atherosclerotic cardiovascular diseases. While the association between smoking and atherosclerosis is well‐established, the underlying mechanisms are incompletely understood. Here, we report an in vivo mouse model of smoking‐induced cardiovascular disorders. Male C57BL/6 mice (8‐weeks) were exposed to whole body mainstream cigarette smoke (CS) by the SCIREQ "InExpose" smoking system (60 min/day, 5 days/week) for 8, 16, or 32 weeks. Mice were sacrificed 24‐hours after the last CS exposure. Blood pressure was measured and cardiac MRI was performed. In vitro aortic ring and isolated heart were used for vascular and cardiac function, respectively. Blood from smoker (SM) and nonsmoker (NSM) mice were investigated for nitric oxide (NO) decay rate and ROS generation. Compared to NSM mice at 32‐weeks of CS exposure (n = 4‐8): SM mice had significant weight loss and hypertension. Acetylcholine‐induced vasorelaxation was markedly shifted to the right and downwards; left ventricular (LV) mass and LV end diastolic volume were significantly larger with increased heart to body‐weight ratio. In the blood of SM mice, NO decay was increased by 15% and white blood cells demonstrated significantly higher ROS. Thus, the present in vivo mouse model provides evidence that CS exposure induces leukocyte activation, NO and endothelial dysfunction, hypertension, and cardiac hypertrophy.