Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression

Preeclampsia is a common and deadly hypertensive disease of pregnancy which primes lifelong maternal and fetal risk for cardiovascular disease and other pathologies. For example, women with a history of preeclampsia have double or more increased risk for future cardiovascular disease including ischemic heart disease, while their children have increased lifetime stroke risk (RR: 1.9) [1], [2], [3]. The mechanisms mediating this increased risk are, however, mostly unknown.

Arginine vasopressin (AVP) is a key player in preeclampsia pathogenesis and is sufficient to cause endophenotypes of preeclampsia in a mouse model, as previously described by our lab [4], [5], [6]. AVP is a nonapeptide that regulates blood pressure and body fluid homeostasis and hemodynamics via binding receptors including AVPR1a, AVPR1b, and AVPR2, as well as the oxytocin receptor (OXTR) and CUL5 (aka VACM-1), a calcium-mobilizing protein activated by AVP. These targets have varying expression across tissues and functions; for instance, AVPR1a is highly expressed in smooth muscle and enables vasoconstriction, while AVPR1b is highly expressed in the pituitary and regulates adrenocorticotropic hormone release. Furthermore, maternal AVP and AVPR expression is disrupted by maternal hypertension in pregnancy, suggesting a mechanism by which gestational hypertension may influence life-long increased risk for cardiovascular disease [4], [5]. However, whether these same mechanisms are implicated in fetal cardiovascular programming is unclear. To address this gap, we assessed how cord blood expression of AVP receptors and LNPEP, which codes for a zinc-dependent aminopeptidase that degrades vasopressin, are impacted by gestational and fetal factors including chronic hypertension in pregnancy, infant sex, and gestational age at delivery.

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