Postpartum assessment of the renin angiotensin system in women with previous severe, early-onset preeclampsia.

CONTEXT: Women with a history of severe preeclampsia are at an increased risk for the development of vascular disease. OBJECTIVE: We hypothesized that abnormalities in the renin-angiotensin system (RAS) may be a predisposing factor. DESIGN AND SETTING: Physiological assessments were conducted at an academic center. PARTICIPANTS: Sixteen women with previous severe preeclampsia (PPE) were compared with nine previously pregnant controls (PPC) and 11 never-pregnant controls (NPC). INTERVENTIONS: Baseline circulating components of the RAS and expression of angiotensin (ANG) II type I (AT1) and type II (AT2) receptors in the skin were assessed along with the response to simulated orthostatic stress using incremental lower-body negative pressure (LBNP: -15, -25, and -40 mm Hg) and a graded ANG II infusion (1 and 3 ng/kg · min). MAIN OUTCOME MEASURES: Response to LBNP and ANG II was evaluated. RESULTS: RAS components were not different between previously pregnant groups, but were decreased compared with NPC subjects. In response to LBNP, there were significant increases in RAS components in all three groups, but the response to this stimulus was significantly lower and delayed in PPE subjects. Despite the blunted rise in circulating RAS mediators in PPE subjects, their blood pressure was maintained in 88% compared with only 33 and 55% in the PPC and NPC groups, respectively (P = 0.014). All three groups responded to the graded ANG II infusion with an increase in blood pressure that was significantly more pronounced in PPE subjects (P = 0.037) correlating with AT1/AT2 receptor expression. CONCLUSIONS: Alterations in the RAS in formerly preeclamptic patients may contribute to future vascular disease.

[Possibilities of laboratory diagnosis in the assessment of the activity of the renin-angiotensin-aldosterone system].

The renin-angiotensin-aldosterone system (RAAS) plays a substantial role in the regulation of many cardiovascular parameters and renal function, including the maintenance of blood pressure and water-salt exchange. The paper describes the most intensively used methods for determining the components of RAAS.

The practical assessment of compliance with ACE-inhibitor therapy--a novel approach.

Poor compliance may be responsible for symptomatic decompensation or neurohormonal "escape" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. Serum ACE activity may, however, be a useful index of compliance with treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the blood. Sixteen normotensive male volunteers of known ACE genotype received 7 days of randomised, double-blind therapy on four occasions 2 weeks apart with lisinopril 20 mg (L) or matched placebo (P) to simulate (A) noncompliance (all P), (B) full compliance (all L), (C) partial compliance (L days, 1, 3, 6; P days, 2, 4, 5, 7), or (D) single dose (L day 7; P, 1-6). Supine (30 min) blood pressure (BP)/heart rate (HR), ACE, and angiotensins were measured on d7 before dose and 4-6 h after dose. Results are mean +/- 1 SD. BP showed the expected small decrease with active treatment on d7 (B or D) but not with placebo (A) or partial compliance (C). Prestudy serum ACE, despite a wide range (16-124 U/L), was reproducible within subjects [coefficient of variation (CV), 1.7%]. Serum ACE activity, before (41.9 +/- 30) and after (41 +/- 30) angiotensin (A) I or II, were unaffected by treatment (placebo A). Active treatment (B) resulted in very low serum ACE activity and d7 and a small further suppression after dosing (before, 3.9 +/- 4; after, 1.8 +/- 4). AI was elevated in this group with further elevation after dosing (before, 234 +/- 116; after, 551 +/- 250). AII was only modestly reduced from baseline and showed little further suppression after dosing (before, 7.8 +/- 4; after, 6.3 +/- 5). Partial compliance (C) showed low ACE but no reduction after treatment (before, 7 +/- 3; after, 7 +/- 4), an elevated AI but no dosing effect (before, 187 +/- 198; after, 200 +/- 151) and reduced AII but with no further dose suppression (before, 6.4 +/- 3.4; after, 7 +/- 4) induced increase in peptide (compared with B). Single-dose treatment (D) showed ACE inhibition as expected (before, 47 +/- 30; after, 2.2 +/- 3). There was a dosing-related increase of AI but to a lesser extent than seen with chronic active dosing (B) (before, 39 +/- 10; after, 240 +/- 200). In contrast to long-term dosing, there was marked ANG II suppression (before, 8.8 +/- 4; after, 2.9 +/- 3). With this long-acting ACEI in a dose relevant to congestive heart failure management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These absolute values may be altered in patients treated concomitant with loop diuretics. In principle, however, this may be a useful tool in clinical trials or in clinical practice after further work has been done to assess the limits in patients across the doses and across the range of available drugs used.