Key result
Progesterone supplementation prevented LPS-induced hypotension in pregnant mice and reduced myocardial inflammatory cytokine gene expression.
Why the study?
Pregnancy exacerbates hypotensive responses to infection and lipopolysaccharide, and high progesterone levels have been suggested to drive these altered cardiovascular responses.
Does progesterone supplementation prevent LPS-induced hypotension in pregnant mice?
Does progesterone supplementation prevent LPS-induced hypotension in pregnant mice?
Progesterone supplementation prevents LPS-induced hypotension and reduces myocardial inflammatory cytokine gene expression in pregnant mice, suggesting a protective cardiovascular effect during sepsis.
Hypothesis-generating for progesterone in pregnancy-associated septic shock; human trials needed before any clinical consideration.
Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and lipopolysaccharide (LPS). The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS.Female CD1 mice had radiotelemetry probes implanted to measure hemodynamic function noninvasively and were time-mated. From day 14 of pregnancy, mice received either 10 mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10 μg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 h.Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar.This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.
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Zöllner et al. (2019) studied LPS-induced hypotension in pregnancy. Progesterone (P4) supplementation vs. Vehicle alone was evaluated on Hypotensive response to LPS (blood pressure). Progesterone supplementation prevented LPS-induced hypotension in pregnant mice and reduced myocardial inflammatory cytokine gene expression.
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