Kinetics of Postpartum Mesenteric Artery Structure and Function Relative to Pregnancy and Lactation in Mice

Abstract

Epidemiological evidence suggests that normal pregnancy in women is associated with decreased cardiovascular risk in later life. Clinical studies have provided evidence that alterations in vascular function and structure are detectable long after delivery. To understand these findings, we examined mesenteric artery reactivity at both early (3 days and 2–4 weeks) and late (12 weeks) postpartum (PP) time points in relation to late pregnancy (LP) and lactation. Vessels from virgin controls, LP, PP, and nursing and non-nursing mothers were tested for responses to phenylephrine (PE), high potassium solutions (high K+), and acetylcholine (ACh). Passive arterial distensibility, vessel dimensions, and collagen and elastin content were evaluated for the studied groups. We observed that (1) there was a significant inhibition of vascular reactivity to PE in LP, 3 days and 2 weeks PP vessels that returned to pre-pregnancy levels at 4 and 12 weeks PP; (2) inhibition of NO production in PP vessels restored PE-induced constriction to pre-pregnancy levels; (3) vasodilator responses to ACh were similar at all PP periods; (4) LP and early PP was associated with a persistent increase in arterial distensibility that correlates with a PP-induced reduction in wall collagen, and regressed to pre-conception levels at 12 weeks PP; (5) vessels from non-nursing PP mice demonstrated an increased PE reactivity, diminished responses to ACh, and reduced distensibility compared to breastfeeding mice. These studies provide a timeframe for mesenteric artery adaptations that occur during pregnancy and extend to the PP period, but which may be modified by PP events.

Deficiency in CD4 T Cells Leads to Enhanced Postpartum Internal Carotid Artery Vasoconstriction in Mice: The Role of Nitric Oxide

“…In our previous studies, mesenteric artery PE-induced constriction was significantly reduced in early PP but was restored to pre-pregnancy levels after inhibition of NO production with L-NNA (Gokina et al, 2021). These data implicate an important modulatory role of NO in regulation of PE-induced mesenteric vasoconstriction in the PP period.…”

“…Our data demonstrate that in both WT and CD4 deficient mice, the PP period is associated with a modest increase in ICA lumen diameters with a potential lag in the case of CD4 deficiency ( Figure 8 ), and with minor changes in passive arterial distensibility. Published data from animal studies as well as clinical data show a significant increase in arterial distensibility in the PP mesenteric vasculature ( Bonney et al, 2017 ; Morris et al, 2020 ; Gokina et al, 2021 ) or increased vascular compliance in PP women ( Morris et al, 2015 ). Modest changes in carotid artery distensibility in the PP period is a novel finding demonstrating significant variations in the effect of pregnancy on the structure of resistance (mesenteric) vs. systemic (internal carotid) arteries.…”

“…We have previously observed that pregnancy significantly modified structural as well as functional parameters in mesenteric vessels of PP mice (Bonney et al, 2017;Gokina et al, 2021). We next turned to examine the effects of pregnancy and CD4 deficiency on the mechanical behavior of ICAs at early and late PP periods.…”

“…Systemic vascular distensibility and vasodilation show a significant increase in order to accommodate maternal blood volume expansion during normal pregnancy ( Magness et al, 1996 ; Magness, 1999 ; Bernstein et al, 2001 ). While the majority of maternal cardiovascular changes are reversible after delivery, some continue in the postpartum period (PP) and thus may modify cardiovascular risk in future pregnancies ( Clapp and Capeless, 1997 ; Morris et al, 2015 ; Staff et al, 2016 ; Bonney et al, 2017 ; Gokina et al, 2021 ).…”

Proteomic Profiling and Pathway Analysis of Acid Stress-Induced Vasorelaxation of Mesenteric Arteries In Vitro

“…Therefore, predicting the risk of acidosis and designing new prophylactic strategies are serious challenges of modern medicine. Mesenteric arteries are systemic, resistance-sized vessels that play an important role in the control of blood pressure and contribute towards the regulation of peripheral vascular resistance [7]. It is expected that any change in the normal physiology of dilatation due to acidosis of mesenteric arteries can affect health.…”