Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis

Abstract

The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: Gq(EC), Gs(SMC), Gq(SMC)). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator Gq(EC) sensitivity (EC(50) reduced by -0.76 [-0.92, -0.60] log[M]) and Gs(SMC) sensitivity (EC(50) reduced by -0.51 [-0.82, -0.20] log[M]), depresses vasopressor Gq(SMC) sensitivity (EC(50) increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated.

Estrogen Receptor Subtypes Mediate Distinct Microvascular Dilation and Reduction in [Ca2+]i in Mesenteric Microvessels of Female Rat

“…Other studies have shown that G1 produces vasodilation similar to E2 in the carotid artery of a Sprague-Dawley rat of both genders (Broughton et al, 2010) and the mesenteric artery of a male SpragueDawley rat (Haas et al, 2009) and female mRen2.Lewis rat (Lindsey et al, 2011). These differences may be related to the rat strain, regional differences in ER distribution along the arterial tree (D'Angelo and Osol, 1993;van Drongelen et al, 2012), and hormonal changes during the estrous cycle, which could influence vascular function, and some of the studies in female rats did not report the stage of the estrous cycle or ] i were constructed in response to increasing concentrations (10 29 to 10 25 M) of E2 (all ERs), PPT (ERa agonist), DPN (ERb agonist), or G1 (GPR30 agonist) in microvessels pretreated with KCI (51 mM) alone (E and G) or KCI (24 mM) plus Bay K 8644 (F and H). Data points represent means 6 S.E.M., n = 4-12.…”

Functional Vascular Changes of the Kidney during Pregnancy in Animals: A Systematic Review and Meta-Analysis

“…One may question the validity of such extrapolations. A previous meta-analysis showed that in mesenteric arteries vascular adaptation to pregnancy is strongly dependent on species, strains and gestational ages [8]. This may also be the case for renal arteries.…”

“…or b. The mediating receptor complex involved [8]. Most studies have concentrated on agents that affect the G-protein coupled receptors.…”

“…Most studies have concentrated on agents that affect the G-protein coupled receptors. These can be divided into three common G-protein coupled receptor pathways: the vasodilator Gq EC -pathway which mediates NO-dependent vasodilation, the vasoconstrictor Gq SMC -pathway which induces a calcium rise in the SMC, and the vasodilator Gs SMC -pathway which induces potassium influx in the SMC [8]–[15].…”

Pregnancy-Induced hypertension

“…47 Such vasodilators include the kallikrein-kinin system, prostacyclin, nitric oxide and vascular-endothelial growth factor (VEGF). [48][49][50] In addition to the functional adaptation of the maternal cardiovascular system, structural changes also occur during pregnancy. This adaptive remodelling results in cardiac hypertrophy that enables the heart to cope with the increased demands of gestation.…”