Cigarette Smoke Exposure Causes Systemic and Autonomic Cardiocirculatory Changes in Rats Depending on the Daily Exposure Dose

Aims: To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day. Main methods: Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis. Key findings: Rats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (-2.2 +/- 0.1 vs. -1.7 +/- 0.2 vs. -1.5 +/- 0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (-25 +/- 4 vs. -28 +/- 4 vs. -56 +/- 9) and lower intrinsic HR (411 +/- 4 vs. 420 +/- 8 vs. 390 +/- 6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia. Significance: CS exposure for 30 days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.