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

<jats:p> <jats:italic>Abstract</jats:italic> —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 <jats:italic>N</jats:italic> <jats:sup>G</jats:sup> -nitro- <jats:sc>l</jats:sc> -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 <jats:sub>1</jats:sub> -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 <jats:sup>2</jats:sup> ) and the high-KCl–induced active stress (0.55±0.09×10 <jats:xref ref-type="bibr"> <jats:sup>4</jats:sup> </jats:xref> N/m <jats:sup>2</jats:sup> ) 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 <jats:xref ref-type="bibr"> <jats:sup>4</jats:sup> </jats:xref> N/m <jats:sup>2</jats:sup> ) was greater than that in virgin rats (0.52±0.1×10 <jats:xref ref-type="bibr"> <jats:sup>4</jats:sup> </jats:xref> N/m <jats:sup>2</jats:sup> ), whereas the high-KCl–induced active stress (1.08±0.14×10 <jats:xref ref-type="bibr"> <jats:sup>4</jats:sup> </jats:xref> N/m <jats:sup>2</jats:sup> ) was indistinguishable from that in virgin rats (1.03±0.14×10 <jats:xref ref-type="bibr"> <jats:sup>4</jats:sup> </jats:xref> N/m <jats:sup>2</jats:sup> ). Treatment with L-NAME did not affect the phenylephrine-releasable Ca <jats:sup>2+</jats:sup> 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 <jats:sup>2+</jats:sup> entry from extracellular space. However, other mechanisms such as increased myofilament force sensitivity to Ca <jats:sup>2+</jats:sup> and/or activation of a completely Ca <jats:sup>2+</jats:sup> -independent mechanism cannot be excluded. </jats:p>