Oral Losartan Treatment Improves Microvascular Endothelial Function via Nitric Oxide-Dependent Mechanisms in Women With a History of Preeclampsia.

Schwartz, Jalal, Stanhewicz. Oral Losartan Treatment Improves Microvascular Endothelial Function via Nitric Oxide-Dependent Mechanisms in Women With a History of Preeclampsia. American journal of hypertension. 2025 Jun 16; 38(7):459-466, DOI: 10.1093/ajh/hpaf033.

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Abstract:

BACKGROUND: Women with a history of preeclampsia are at increased risk of developing cardiovascular disease compared with women who had a healthy pregnancy. One potential mechanism underlying this increased risk is microvascular endothelial dysfunction, characterized by reduced nitric oxide (NO)-dependent dilation and is mediated, in part, by increased vasoconstrictor sensitivity to angiotensin II, which persists postpartum. We hypothesized that systemic angiotensin II type 1 receptor (AT1R) inhibition via once-daily oral losartan treatment would (1) improve endothelium- and NO-dependent dilation, and (2) reduce angiotensin II-mediated vasoconstriction, in the microvasculature of women with a history of preeclampsia. METHODS: Eleven normotensive women, > 12 weeks and ≤5 years postpartum, with a history of preeclampsia participated in a double-blind, placebo-controlled, crossover study. Following 6 weeks of placebo and losartan treatment (50 mg/day), we measured cutaneous vascular conductance responses to graded infusions of acetylcholine (ACh, 10-10-10-1 M) alone or with 15 mM NG-nitro-l-arginine methyl ester (L-NAME; NO-synthase inhibitor) to assess endothelium- and NO-dependent dilation, respectively. We also assessed microvascular vasoconstrictor responses to graded infusions of angiotensin II (10-20-10-4 M) and norepinephrine (10-12-10-2 M). RESULTS: Losartan treatment increased endothelium- (P  <  0.001) and NO-dependent (P  <  0.016) vasodilation compared with placebo. Losartan treatment also reduced angiotensin II-mediated vasoconstriction (P  <  0.001) compared with placebo, but had no effect on norepinephrine-mediated vasoconstriction (P  =  0.46). CONCLUSIONS: These data suggest that systemic AT1R-inhibition with oral losartan is a viable, mechanism-specific approach to improve endothelial function and reduce vasoconstrictor sensitivity to angiotensin II in the microvasculature of healthy, normotensive women with a history of preeclampsia.