Nicotine Dose Dependently Uncovers Endotoxic Cardiovascular Manifestations of Hypotension and Autonomic Dysfunction in Female Rats

The inflammatory and cardiovascular effects of endotoxemia are dampened down in the female gender due possibly to the immune boosting actions of female sex steroids. Considering that tobacco constituents including nicotine inhibit estrogen synthesis, we tested the hypothesis that nicotine exposure unveils cardiovascular anomalies of endotoxemia in conscious female rats. Hemodynamic and cardiac autonomic profiles were assessed in female rats treated with i.v. lipopolysaccharide (LPS, 10 mg/kg) in the absence and presence of nicotine. Cardiac autonomic function was assessed via time‐ and frequency‐domain analyses of heart rate variability (HRV). In contrast to no effects for i.v. LPS in female rats when used alone over a period of 3 hr, significant and dose‐related decreases and increases in blood pressure (BP) and heart rate (HR), respectively, were seen in rats when nicotine (25, 50, or 100 μg/kg i.v.) was co‐administered with LPS. Signs of cardiac autonomic dysfunction appeared in LPS/nicotine‐treated rats such as decreased time‐domain indices of HRV indices including the standard deviation of beat‐to‐beat intervals (SDRR) and the root mean square of successive beat‐to‐beat differences in R‐R interval durations (rMSSD). Additionally, spectral analysis revealed that the LPS/nicotine regimen (i) reduced the total power of the frequency spectrum, (ii) caused distinct changes in the R‐R oscillations in low‐frequency (LF, increases) and high‐frequency (HF, decreases) ranges, and (iii) shifted the cardiac sympathovagal balance toward sympathetic dominance as indicated by the increases in LF/HF ratios. The reflex autonomic control does not appear to contribute to the nicotine effects because baroreflex dysfunction induced by LPS was preserved after nicotine treatment. Serum estrogen, but not progesterone, levels were reduced by nicotine in a dose‐dependent manner. Together, the data suggest that nicotine acts apparently via reducing estrogen availability to expose the hypotensive and autonomic dysregulating actions of LPS in the female population. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .