Maternal hypertension and cardiovascular medications dysregulate placental arterial tone

Abstract Antihypertensive and cardiac medications prescribed to pregnant women, including Ca 2+ channel blockers (CCBs), α- and β-adrenergic receptor antagonists, and α-adrenergic receptor agonists enter the fetal circulation, with unknown effects on the fetoplacental vasculature. We investigated whether these medications alter human fetoplacental vascular tone and placental perfusion. Chorionic plate arteries (CPAs) were obtained from placentas of normotensive women, women with unmedicated hypertension, and those receiving amlodipine, nifedipine, labetalol or bisoprolol, or CCB–labetalol combinations. Using wire myography, acute effects of amlodipine, nifedipine, labetalol, methyldopa, doxazosin, bisoprolol and nebivolol were tested in pre-constricted CPAs from normotensive women. Vascular reactivity following chronic hypertension and/or medication exposure was assessed by vasoconstriction to high potassium physiological solution (KPSS) and U46619, and by relaxation to sodium nitroprusside (SNP). Acute ex vivo exposure to amlodipine, nifedipine, doxazosin and nebivolol promoted vasorelaxation, while labetalol, methyldopa and bisoprolol increased vasoconstriction relative to controls. A history of chronic hypertension and exposure to bisoprolol-treatment during pregnancy was associated with attenuated vascular responses to U46619 and SNP. Maternal hypertension is associated with abnormal placental vascular function, and cardiovascular medications may further dysregulate fetoplacental vascular reactivity, with potential implications for pregnancy outcomes. Mechanistic studies alongside clinical correlations are essential to guide evidence-based prescribing.