Reduced plasma levels of angiotensin-(1-7) and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

Abstract

The relationship between preeclampsia and the renin-angiotensin system (RAS) is poorly understood. Angiotensin I-converting enzyme (ACE) is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II) and inactivating the vasodilator angiotensin-(1-7) (Ang-(1-7)). ACE (I/D) polymorphism is characterized by the insertion (I) or deletion (D) of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D) polymorphism was correlated with plasma Ang-(1-7) levels and several RAS components in both preeclamptic (N = 20) and normotensive pregnant women (N = 20). The percentage of the ACE DD genotype (60%) in the preeclamptic group was higher than that for the control group (35%); however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260). The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 +/- 5.06 vs 27.6 +/- 3.25 nmol Hip-His Leu(-1) min(-1) mL(-1) in DD control patients; P = 0.0005). Plasma renin activity was markedly reduced in preeclampsia (0.81 +/- 0.2 vs 3.43 +/- 0.8 ng Ang I mL plasma(-1) h(-1) in DD normotensive patients; P = 0.0012). A reduced plasma level of Ang-(1-7) was also observed in preeclamptic women (15.6 +/- 1.3 vs 22.7 +/- 2.5 pg/mL in the DD control group; P = 0.0146). In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…Expression of MAS in uterus and placenta is thought to be relevant to diseases such as preeclampsia (Velloso et al, 2007). Thus, MAS may not be important modulator of male and female fertility but may be relevant in pathogenesis related to fertility.…”

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

“…9 Physiological relevance of the Ang-(1-7)/AT1-R axis could be, however, questioned given that the affinity/potency of Ang-(1-7) for AT1-R is modest (≈300 nmol/L) and relatively far from plasma concentrations generally described, with significant differences in between rodents (nmol/L) 26,27 or human species (pM). [28][29][30] Nevertheless, despite the RAAS was originally described as a circulating system, it is now widely accepted that a distinct local RAAS does exist in several tissues, 31 thus promoting a close ligand-receptor proximity to ensure an accurate spatiotemporal regulation of RAAS actions similar to that observed for neurotransmitters concentrations in the synaptic cleft after release. 32 In line with this assumption, Ang II levels were quantified >100-fold higher in interstitial fluid of the heart than plasma levels.…”

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

“…Zhou et al (43) and Zhu et al (44) reported the association of ACE I/D polymorphism and preeclampsia in Chinese women, and other studies reported an association of ACE genotypes with preeclampsia in Turkish and Korean females (43, 44). Velloso et al (45) suggested that the ACE DD genotype might be used as a marker for susceptibility to preeclampsia in Brazilian women. Li et al (45) reported from China, that ACE gene I/D polymorphism were associated with the severe proteinuria and renal dysfunction seen in preeclampsia and preeclamptic patients carrying the D allele might be susceptible to renal dysfunction.…”