The Provoked Cardiovascular and Autonomic Effects of Endotoxemia in Ovariectomized Rats Are Distinctly Affected by Estrogen and Progesterone Supplementation

Abstract

The female gender is protected against immunological and cardiovascular complications of sepsis. This study investigated whether gonadal hormone depletion by bilateral ovariectomy (OVX) could uncover the cardiovascular and autonomic effects of endotoxemia and whether these effects can be reversed by hormone replacement therapies. Changes in blood pressure (BP), heart rate variability (HRV), and left ventricular (LV) function caused by i.v. administration of lipopolysaccharide (LPS, 10 mg/kg) were evaluated in conscious female rats with different hormonal states. While LPS caused no specific cardiovascular effects in intact female rats, LPS‐treated OVX rats exhibited significant decreases in blood pressure (BP) and increases in spectral low‐frequency/high‐frequency ratio (LF/HF) of HRV, denoting enhanced cardiac sympathetic dominance. Moreover, LPS increased the rate of rise in LV pressure (dP/dtmax, LV contractility) without affecting the isovolumic relaxation constant (Tau, a measure of diastolic function). LPS hypotension was totally eliminated in OVX rats pretreated with estrogen but not medroxyprogesterone acetate (MPA). Prior selective activation of estrogen receptor‐α (4,4′,4″‐(4‐Propyl‐[1H]‐pyrazole‐1,3,5‐triyl)trisphenol, PPT) or estrogen receptor‐β (Diarylpropionitrile, DPN) partially counteracted LPS hypotension. Each of the abovementioned drug treatments (estrogen, MPA, PPT, or DPN) abrogated the LPS‐evoked exaggeration in cardiac sympathetic control (LF/HF ratio). By contrast, the elevated dP/dtmax in LPS‐treated rats was largely compromised by PPT only. The data suggest differential modulatory roles for gonadal hormones (estrogen and progesterone) and estrogen receptors (α and β) on endotoxic cardiovascular and autonomic manifestations in female rats.Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.