The Vasodilatory Effects of Hydralazine, Nicardipine, Nitroglycerin, and Fenoldopam in the Human Umbilical Artery

Abstract

We studied the effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam (a dopamine D1-agonist) on isolated human umbilical arteries (HUA) from patients classified as normotensive and with pregnancy-induced hypertension (PIH). Umbilical artery rings were contracted with the thromboxane A(2) analog (U46619; 10(-8) M) and then exposed to cumulative concentrations of fenoldopam, hydralazine, nicardipine, and nitroglycerin. Second, rings were preexposed to prazosin (10(-5) M), phenoxybenzamine (10(-5) M), or none, and the constriction responses to increasing doses of fenoldopam or dopamine were recorded. Nitroglycerin, hydralazine, and nicardipine produced concentration-dependent relaxation of U46619-preconstricted HUA segments from normotensive and PIH patients. Fenoldopam and dopamine induced umbilical artery constriction in both normal and PIH rings at concentrations > or = 10(-5) M and > or = 10(-3) M, respectively. Phenoxybenzamine, but not prazosin, pretreatment irreversibly abolished fenoldopam-induced contraction. In this in vitro study, nitroglycerin was the most potent vasodilator of the HUA constricted with U46619, followed by nicardipine and hydralazine. However, fenoldopam constricted HUA rings only at supratherapeutic concentrations. No significant differences of vascular responses to fenoldopam (P = 0.3534), nitroglycerin (P = 0.7416), nicardipine (P = 0.0615), and hydralazine (P = 0.5514) between rings from normotensive or hypertensive pregnant patients were shown.

Transdermal nitroglycerin in patients with severe pre‐eclampsia with placental insufficiency: effect on uterine, umbilical and fetal middle cerebral artery resistance indices

“…Nitric oxide is a small molecule that easily crosses the placenta28, and is known to cause dilation of the umbilical vessels in vitro 19. The decrease in umbilical artery resistance to blood flow seen in the current study had been previously reported with both sublingual and intravenous administration routes10, 18.…”

“…Doppler velocimetry is a non‐invasive method used to evaluate resistance to blood flow in the uteroplacental and fetoplacental circulations. Previous smaller studies have suggested a potential benefit of GTN in patients with pre‐eclampsia or placental insufficiency17–22.…”

In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery

“…We have reported previously that fenoldopam could induce a-adrenergic stimulation and cause vasoconstriction of human umbilical artery. 11 In the current study, however, we did not observe vasoconstriction at comparable concentrations. In the study by Hughes and colleagues, fenoldopam effectively reversed norepinephrine-or prostaglandin F 2a -induced contraction on renal, gastric=splenic artery, and colic artery with EC 50 (1.4-2.9·10 À6 M).…”

“…1). 11 We have reported previously a similar difference between GTN and a short-acting calcium channel blocker, clevidipine. 12 Nicorandil, an ATP sensitive K + channel opener, also exerted vasodilation (71.7%) of human IMA, which is in agreement with others, 13 and its potency was similar to nicardipine.…”

Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness

“…In human umbilical arteries, fenoldopam induces vasoconstriction at supratherapeutic concentrations. This effect can be blocked by the irreversible alpha-adrenergic receptor antagonist phenoxybenzamine but not the reversible antagonist phentolamine (34). We previously examined the effects of systemic fenoldopam infusion in preterm and near-term fetal sheep.…”