Influence Of Sub-Chronic Cigarette Smoke Exposure On The Progression Of Myocardial Hypertrophy In Spontaneously Hypertensive Rats (SHR)

In search of an experimental model for cardiac risk by smoking we exposed 8-week old male SHR to cigarette mainstream smoke (MS) from the Kentucky reference cigarette 2R4F (450 µg total particulate matter/l) or to fresh air (sham) for 30, 60, and 90 days (2 hours/day, 5 days/week) to investigate the development of myocardial hypertrophy (heart/body weight ratio, mRNA expression of hypertrophy markers via real-time RT-PCR, and protein expression via immunoblots). Basal heart function was determined in vitro by Langendorff-perfusion. Blood pressure and heart rate were monitored in vivo via telemetric analysis. Due to a reduced increase in body weight, the MS groups had an approximately 20% larger increase in heart/body weight ratio after just 30 days (5.83 ± 0.29 versus 4.94 ± 0.35 mg/g; p<0.01) accompanied by elevated basal heart function (left ventricular developed pressure: 103.9 ± 5.9 vs. 83.3 ± 6.5 mm hg, p<0.01). The mRNA expression of myocardial hypertrophy markers, i.e., atrial natriuretic factor, ornithine decarboxylase, and TGF-β, increased in both ventricles (more pronounced at 90 days than at 30 days). In the sham groups these markers were less increased in the left ventricle and did not change over time in the right ventricle. Increases in ANF and TGF-β were confirmed on the protein level in the 90-day MS group. There were no measurable differences for blood pressure or heart rate between MS and sham groups. The mRNA expression for calcium-handling proteins (SERCA2a and NCX) did not change. At the same time, there was less p-adrenergic response in heart function to isoprenaline (100 nm). SHR exposed to MS showed a faster progression of myocardial hypertrophy with a reduction in β-adrenergic response. This effect is independent of hypertension and occurs in both ventricles. The data suggest the acceleration of cardiac dysfunction development by sub-chronic MS exposure in rats.