Chronic Nitric Oxide Synthesis Inhibition Does Not Prevent Pregnancy Vasodilation in the Rat

Abstract

Objective: To determine if blockade of endothelium-derived nitric oxide synthesis from the day after embryo implantation to the day before parturition prevents maternal systemic vasodilation in the rat.

Methods: Timed-pregnant and age-matched nonpregnant Wistar-Kyoto rats were administered the nonselective nitric oxide synthase inhibitor N^w-nitro-L-arginine methyl ester (15 mg/rat/day, s.c.) or saline vehicle (untreated) for 14 days using osmotic minipumps. On the last day of treatment (day 20 of gestation in the pregnant rats), plasma total nitrate/nitrite concentration, mean arterial blood pressure, and heart rate were measured. Cardiac output and organ blood flows were then measured using radioactive-labeled microspheres for the calculation of total systemic and organ/tissue vascular conductances, respectively.

Results: Chronic blockade of nitric oxide synthesis decreased plasma nitrate/nitrite concentration >90% and induced hypertension with decreased cardiac output and organ blood flows in both nonpregnant and pregnant rats. Cardiac output and total vascular conductance were significantly increased in the pregnant compared to nonpregnant, untreated normotensive rats and in nitric-oxide-blocked hypertensive rats. Vascular conductance of the skin, skeletal muscle/skeleton, gastrointestinal tract, heart, and uterus were significantly greater in pregnant than in nonpregnant rats of both treatment groups.

Conclusions: Maternal systemic and uterine vasodilation during pregnancy is complex and is caused by some mechanism(s) other than increased basal endothelium-derived nitric oxide production or by a compensatory increase in some other vasodilatory system during nitric oxide synthesis blockade.

Key Words:

• Blood pressure
• Pregnancy
• Vascular conductance
• Nitric oxide
• Pregnancy hypertension
• Rat