Role of Corin in Blood Pressure Regulation in Normotensive and Hypertensive Pregnancy

Abstract

Corin (an atrial natriuretic peptide converting enzyme) represents a potential biomarker for gestational hypertensive disorders; yet, its role in blood pressure regulation throughout pregnancy remains unclear. We investigated the time-course of change in blood corin content in relation to blood pressure and sympathetic nerve activity throughout pregnancy. Forty-four women (29±0.9 yrs) participated. Following-term, 23 had 'low-risk' (no personal history of gestational hypertensive disorders) normal pregnancies, 13 had 'high-risk' (personal history of gestational hypertensive disorders) normal pregnancies, and eight developed gestational hypertension. Blood pressure, heart rate, muscle sympathetic nerve activity, and serum corin were measured prior-to pregnancy, during early-(4-8 wks) and late-pregnancy (32-36 wks), and post-partum (6-10 wks). Overall, compared to pre-pregnancy, corin remained unchanged during early-pregnancy, increased markedly during late-pregnancy (P<0.001), and returned to pre-pregnancy levels post-partum. In women who developed gestational hypertension, the change in corin from early-to late-pregnancy was greater than those with 'low-risk' normal pregnancies (Δ971±134 vs. Δ486±79 pg/mL; P<0.05). Throughout pregnancy, blood pressure and muscle sympathetic nerve activity were augmented in women with gestational hypertension (all P<0.05). Finally, changes in corin from early-to late-pregnancy were related to all indices of blood pressure (R=0.454-0.551; all P<0.01) in late-pregnancy, whereas burst frequency, burst incidence, and total muscle sympathetic nerve activity (R=0.576-0.614; all P<0.001) in early-pregnancy were related to changes in corin from early-to late-pregnancy. Corin plays a unique role in blood pressure regulation throughout

Sex differences in sympathetic activity in obesity and its related hypertension

“…Indeed, our recent longitudinal study showed that women who developed gestational hypertension had similar height but much greater body weight compared with women who had normotensive pregnancies (e.g., the mean difference in body weight between the groups prior to and during pregnancy was about 28 kg). 97 Furthermore, throughout early and late pregnancy, as well as postpartum, resting MSNA was significantly greater in women with gestational hypertension than in women with normotensive pregnancies (Fig. 6).…”

“…6). 97 Studies from our laboratory and others have suggested that normal pregnancy is associated with sympathetic activation that occurs in the first trimester, sustains throughout the entire course of gestation, and returns to the prepregnancy level after delivery [97][98][99][100][101][102][103] while sympathetic overactivity may lead to the development of gestational hypertensive disorders. 97,100,104…”

Influence of multiparity on sympathetic nerve activity during normal pregnancy

“…The mechanism(s) responsible for this increased risk are likely multifaceted but may in part be due to altered withinpregnancy sympathetic neural regulation in women with multiple pregnancies. Certainly, sympathetic nerve activity (SNA) is augmented (in the range of 50 to 150%) throughout normal pregnancy, occurring as early as 6 wk gestation and peaking within the second or third trimester, as a means to ensure adequate cardiovascular homeostasis (1,6,7,10,15). Yet, when such activation occurs in excess, hypertensive disorders of pregnancy likely manifest, i.e., gestational hypertension and/or preeclampsia (1,2,13).…”

“…Certainly, sympathetic nerve activity (SNA) is augmented (in the range of 50 to 150%) throughout normal pregnancy, occurring as early as 6 wk gestation and peaking within the second or third trimester, as a means to ensure adequate cardiovascular homeostasis (1,6,7,10,15). Yet, when such activation occurs in excess, hypertensive disorders of pregnancy likely manifest, i.e., gestational hypertension and/or preeclampsia (1,2,13). Similarly, sympathetic overactivity is associated with cardiovascular pathology in nonpregnant populations, including hypertension, coronary artery disease, heart failure, etc.…”

Atrial natriuretic peptide promotes uterine decidualization and a TRAIL-dependent mechanism in spiral artery remodeling

“…In mice, corin deficiency abolishes ANP activation (25,26). Both corin and ANP are expressed in the pregnant uterus (27)(28)(29)(30)(31). In mice, corin or ANP deficiency impairs trophoblast invasion and spiral artery remodeling, leading to a preeclampsialike phenotype (27,28,32).…”