Hypertensive disorders and proteinuria are heightened in obese pregnancies, attributed partly to hyperleptinemia. Leptin, associated with obesity, correlates positively with body fat and is elevated in hypertensive pregnant women. Endothelial dysfunction, linked to obesity and hypertensive disorders of pregnancy, implicates inflammatory mediators. Leptin administration induces proteinuria and hypertension during pregnancy, possibly via endothelial activation pathways. ACE2, a counter-regulator to ACE, shows promise in cardiovascular diseases. Its expression increases in normal pregnancy, yet its role in pathological pregnancies remains uncertain. We hypothesized that leptin-induced hypertension involves altered ACE2 activity and expression.
This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure(SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injections of either saline, or leptin, or leptin plus xanthenone(ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; their gene expressions were also determined in the kidney and aorta, respectively. Compared to the control, SBP was higher in the leptin-only treated group (P < 0.001) and lower in rats treated with xanthenone alone (P < 0.01). Proteinuria and markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P < 0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P < 0.05).
In summary, leptin administration during pregnancy-induced hypertension and proteinuria, accompanied by alterations in serum biomarkers and gene expressions associated with endothelial activation. Co-administration of XTN mitigated these effects, suggesting a potential therapeutic role for ACE2 activation in pregnancy-related complications. Further investigations are warranted to elucidate these findings' underlying mechanisms and clinical implications.