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(Hypertension. 1998;31:1065-1069.)
© 1998 American Heart Association, Inc.

Scientific Contributions

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

Raouf A. Khalil; Janice K. Crews; Jacqueline Novak; Salah Kassab; ; Joey P. Granger

From the Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center (Jackson).

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 ₁-adrenergic stimulation with phenylephrine and membrane depolarization by high KCl. In pregnant rats, the maximal active stress to phenylephrine (0.31±0.03x104 N/m²) and the high-KCl–induced active stress (0.55±0.09x10⁴ N/m²) were smaller than those in virgin rats. By contrast, in the L-NAME–treated pregnant rats, the maximal phenylephrine-induced active stress (0.76±0.1x10⁴ N/m²) was greater than that in virgin rats (0.52±0.1x10⁴ N/m²), whereas the high-KCl–induced active stress (1.08±0.14x10⁴ N/m²) was indistinguishable from that in virgin rats (1.03±0.14x10⁴ N/m²). Treatment with L-NAME did not affect the phenylephrine-releasable Ca²⁺ 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 -adrenergic stimulation, which can possibly be explained in part by enhanced Ca²⁺ entry from extracellular space. However, other mechanisms such as increased myofilament force sensitivity to Ca²⁺ and/or activation of a completely Ca²⁺-independent mechanism cannot be excluded.

Key Words: blood pressure • calcium • muscle, smooth • contraction

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