Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

摘要

Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32–36 weeks) pregnancy, and post-partum (6–10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min⁻¹ and 16 ± 5 vs. 30 ± 3 bursts min⁻¹ in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min⁻¹ at 60 deg ti P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal–adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy.Key points class="unordered" style="list-style-type:disc"> Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian women. This is the first longitudinal study to investigate neural and humoral responses during pregnancy in Asians and Caucasians. The key finding was that Asians had attenuated sympathetic activation but enhanced renal–adrenal responsiveness during pregnancy compared to Caucasians. These results may provide insights into the pathophysiological mechanisms for racial differences in the prevalence of hypertensive disorders during pregnancy. class="head no_bottom_margin" id="__sec2title">IntroductionHypertensive disorders of pregnancy affect up to 10% of pregnant women worldwide. Gestational hypertension occupies 25% of all antenatal admissions (Roberts et al. ), and sometimes it leads to a serious condition − preeclampsia, one major cause of maternal, fetal and neonatal death. The mechanism(s) underlying these medical conditions are still unknown. Recently, it was reported that Asian women had a lower prevalence of hypertensive disorders in pregnancy than any other races and their odds ratio compared with Caucasian women was 0.41 (Cabacungan et al. ). However, how blood pressure (BP) is regulated during normal pregnancy in Asian vs. Caucasian women is unknown.Sympathetic neural control plays a critical role in BP maintenance through a baroreflex-mediated mechanism in humans (Johnson et al. ; Wallin & Sundlof, ; Fu et al. , ). Previous cross-sectional studies showed that muscle sympathetic nerve activity (MSNA) during late pregnancy was greater in pregnant women than non-pregnant women (Greenwood et al. ), while it was greater in hypertensive than normotensive pregnant women (Schobel et al. ; Greenwood et al. , ). Longitudinal studies from our laboratory demonstrated that sympathetic activation occurs even during early pregnancy in healthy women (Jarvis et al. ). These results suggest that sympathetic activation during pregnancy may help to keep BP at the pre-pregnancy level; however, when sympathetic activation is excessive, hypertension may ensue (Greenwood et al. ). So far there is no information available regarding racial differences in sympathetic neural control during normal pregnancy as well as during hypertensive pregnancy.In addition to neural control, renal–adrenal responsiveness also contributes importantly to BP regulation during pregnancy. Maternal plasma renin level becomes higher than the non-pregnant level (Skinner et al. ; Derkx et al. ) even in early pregnancy (Jarvis et al. ). Angiotensinogen synthesis increases with oestrogen (Skinner et al. ; Immonen et al. href="#b25" rid="b25" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897458">1983), resulting in increased angiotensin II and aldosterone (Jarvis et al. href="#b27" rid="b27" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897423">2012). Despite the upregulated renal–adrenal system and aldosterone-induced blood volume expansion, blunted vasoconstrictor responses to angiotensin II and a profound systemic vasodilatation associated with normal pregnancy (Abdul-Karim & Assalin, href="#b1" rid="b1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897418">1961; Chapman et al. href="#b5" rid="b5" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897473">1998; Irani & Xia, href="#b26" rid="b26" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897430">2011; Gennari-Moser et al. href="#b13" rid="b13" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897455">2014) may contribute to the reduction or maintenance of BP in normotensive pregnant women. Recent research showed that high aldosterone availability increased BP in non-pregnant but not pregnant women (Escher et al. href="#b9" rid="b9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897420">2009; Gennari-Moser et al. href="#b13" rid="b13" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897429">2014). In women with gestational hypertension or preeclampsia, enhanced vasoconstrictor responses to angiotensin II, low levels of aldosterone, and small blood volume have been observed (Yang et al. href="#b50" rid="b50" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_434897422">2013), indicating that dysregulation of the renal–adrenal system may be involved in the pathogenesis of hypertensive disorders during pregnancy. The small blood volume could be one contributing factor for sympathetic overactivity in hypertensive disorders of pregnancy. Whether Asians and Caucasians have different renal–adrenal responses during normal pregnancy and hypertensive pregnancy remains unclear.Based on previous findings showing that hypertensive pregnant women have sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low levels of aldosterone), we hypothesized that Asians would have lower MSNA and greater aldosterone concentrations during normal pregnancy than Caucasians. To test this hypothesis, we prospectively studied a group of pre-menopausal healthy Asian and Caucasian women before, during and after their pregnancies.