1. Angiotensin II/Angiotensin (1-7) ratio and 24-h blood pressure throughout the menstrual cycle and in women using oral contraceptives
Gina C Davis, Karen J Gibson, David Casley, Mark A Brown J Hypertens . 2017 Jun;35(6):1178-1186. doi: 10.1097/HJH.0000000000001310.
Background:Women using oral contraceptives have higher ambulatory blood pressures (BPs) than other women. We sought to learn whether this was associated with an alteration in the balance of angiotensin II (Ang)/Ang (1-7) and whether this ratio and BP remained constant throughout the menstrual cycle.Method:In total, 30 (15 ovulatory, 15 taking oral contraceptives) healthy, normotensive women aged 18-30 years were studied. The ovulatory group was assessed within days 1-5 (follicular phase) and 19-23 (luteal phase) and the oral contraceptive group within days 19-23. Peripheral, central and 24-h BP, vascular wall stiffness, and body composition were measured along with plasma estradiol, progesterone, renin, aldosterone, Ang II, and Ang (1-7) concentrations.Results:In ovulatory women plasma renin activity (P < 0.001), renin concentration (P < 0.01) and aldosterone (P < 0.05) were higher in the luteal than follicular phase, whereas BP, Ang II and the Ang II/Ang (1-7) ratio remained constant. In women taking oral contraceptives, plasma renin activity (P < 0.001) and concentration (P < 0.01) were higher than in follicular phase ovulatory women whereas 24-h BP, Ang II, Ang (1-7), and the Ang II/Ang (1-7) ratio (P < 0.01) were higher than in both phases of the ovulatory group. However, there was no significant correlation between BP and the Ang II/Ang (1-7) ratio.Conclusion:This study confirms that BP is constant throughout the normal menstrual cycle along with a constant balance between the vasoconstrictor (Ang II) and vasodilator [Ang (1-7)] arms of the renin-Ang-aldosterone system. Women taking oral contraceptives have a higher Ang II/Ang (1-7) ratio associated with their BP elevation although no causal relationship has been found.
2. Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in cultured rat aortic smooth muscle cells
A Maseri, G Sperti, F Andreotti, A Kol, R T van Leeuwen, C Kluft Circulation . 1994 Jul;90(1):362-8. doi: 10.1161/01.cir.90.1.362.
Background:The role of angiotensin as a vasoconstrictor is well established. Lately, several other actions of this hormone on vascular smooth muscle (VSM) cells have been recognized including the induction of hypertrophy and/or DNA synthesis. Platelet-derived growth factor (PDGF), a mitogen recently shown to increase plasminogen activator inhibitor type 1 (PAI-1) synthesis in VSM cells, shares with angiotensin II (Ang II) several steps of its intracellular signaling pathway.Methods and results:The expression of PAI-1 and tissue-type plasminogen activator (TPA) mRNA in cultured rat VSM cells was studied. Northern blot analysis demonstrated a severalfold increase in the PAI-1 mRNA 3 to 8 hours after stimulation with 300 nmol/L Ang II. A similar response for TPA mRNA was observed. This induction did not require the synthesis of an intermediate protein or peptide because it was not affected by cycloheximide. In the cell-conditioned supernatant, the net result was an increase in PAI-1 activity from 4.18 +/- 1.8 to 13.2 +/- 6.8 IU/mL 6 hours after the addition of 300 nmol/L Ang II (mean +/- SD, P < or = .008, n = 6). The Ang II-induced increase in PAI activity was dose related, with a maximal effect at a concentration of 23 nmol/L (n = 3) and an ED50 of 3.3 +/- 1.5 nmol/L (n = 3). [Sar1-Ile8]angiotensin II, a specific competitive antagonist of Ang II, blocked 90 +/- 9% (n = 3) of the PAI activity induced by 10 nmol/L Ang II. In basal conditions, fibrin overlay zymography demonstrated the presence of free TPA. After stimulation with Ang II, lysis caused by the in situ dissociation of TPA was also present in the region of the TPA/PAI-1 complex. Angiotensin I (Ang I) elicited an increase in PAI activity similar to that obtained with equivalent doses of Ang II. Captopril (5 micrograms/mL), an inhibitor of the angiotensin-converting enzyme (ACE), completely prevented the Ang I effect, demonstrating that VSM cells display an ACE-like activity.Conclusions:Recent research has demonstrated the existence of a localized vascular renin-angiotensin system. The finding that Ang II can potentially modulate the plasminogen activation in the arterial wall has important biological and therapeutical implications for the evolution of arterial wall thrombi and the migration of cells through the vessel wall in the genesis of atherosclerotic lesions. We speculate that the reduction in thrombotic events observed in patients with a previous myocardial infarction and in high-renin, hypertensive patients treated with ACE inhibitors could be due at least in part to the decreased production of PAI-1 by VSM cells caused by these agents.
3. Reduced plasma levels of angiotensin-(1-7) and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype
R Vieira, E Kalapothakis, E P Velloso, R A S Santos, A C Cabral Braz J Med Biol Res . 2007 Apr;40(4):583-90. doi: 10.1590/s0100-879x2007000400018.
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.
