Urinary Angiotensin-(1-7), a Novel Vasodilator, Increases Throughout Normal Pregnancy
The mechanisms involved in the maintenance of normotensive gestation are poorly understood. In the face of marked increases of the potent pressor renin-angiotensin-aldosterone system (RAAS), precise endogenous counterbalancing mechanisms have been described in both systemic and uteroplacental beds. During pregnancy elevations of nitric oxide (NO), prostacyclin (PGI2), and kallikrein activity have been demonstrated. Angiotensin (Ang)-(1-7) is a novel functional member of the RAAS which exerts a vasodilatory effect by stimulating the release of NO, PGI2, and bradykinin. To test the hypothesis that Ang-(1-7) contributes to the vasodilatory effects of normal gestation and exerts a counterbalancing effect on the increased synthesis of Ang II, 24 hour urinary excretion of Ang I, Ang II, and Ang-(1-7) were evaluated during the ovulatory menstrual cycle (MC) and during singleton normotensive pregnancies and lactation (L) in 2 Groups of normotensive, nonproteinuric women (Group 1: 9 cycling women of 33 ± 5 years and Group 2: 10 women of 27 ± 4 years with a normal pregnancy). Urinary Ang-(1-7) (Figure) showed a progressive rise along gestation. Urinary Ang II also rose from weeks 12-13, reaching values at 33-36 weeks that were 24-fold greater than normal MC [Ang II; 240 ± 68 vs 9 ± 1 pmol/g creatinine, p<0.01]. The urinary excretion of Ang I remained stable throughout pregnancy. This first characterization of Ang-(1-7) in the urine of mid and late pregnancy reveals its potential for acting as a vasodilator hormone through a mechanism that may in part relate to its enhanced renal synthesis and as a counterbalancing factor in normal pregnancy.