Enhanced Vascular Reactivity During Inhibition of Nitric Oxide Synthesis in Pregnant Rats

Abstract

Abstract —Pregnancy-induced hypertension has been suggested to be mediated by several mechanisms, including reduced nitric oxide (NO) synthesis. In this study, the effects of chronic treatment with the NO synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME) on blood pressure and the underlying changes in vascular reactivity were investigated in virgin and late-pregnancy Sprague-Dawley rats. The systolic blood pressure was 120±2, 124±5, 116±4, and 171±5 mm Hg in untreated virgin, virgin treated with L-NAME, untreated pregnant, and pregnant treated with L-NAME rats, respectively. The rats were killed, and the thoracic aorta was cut into strips for measurement of active stress in response to α 1 -adrenergic stimulation with phenylephrine and membrane depolarization by high KCl. In pregnant rats, the maximal active stress to phenylephrine (0.31±0.03×104 N/m 2 ) and the high-KCl–induced active stress (0.55±0.09×10 4 N/m 2 ) were smaller than those in virgin rats. By contrast, in the L-NAME–treated pregnant rats, the maximal phenylephrine-induced active stress (0.76±0.1×10 4 N/m 2 ) was greater than that in virgin rats (0.52±0.1×10 4 N/m 2 ), whereas the high-KCl–induced active stress (1.08±0.14×10 4 N/m 2 ) was indistinguishable from that in virgin rats (1.03±0.14×10 4 N/m 2 ). Treatment with L-NAME did not affect the phenylephrine-releasable Ca 2+ stores in pregnant rats and had minimal effect on active stress in virgin rats. Thus, reduction of NO synthesis during late pregnancy is associated with a significant increase in blood pressure and vascular responsiveness to α-adrenergic stimulation, which can possibly be explained in part by enhanced Ca 2+ entry from extracellular space. However, other mechanisms such as increased myofilament force sensitivity to Ca 2+ and/or activation of a completely Ca 2+ -independent mechanism cannot be excluded.