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Nω-Nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents

  • Author Footnotes
    * From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine.
    Miklós Molnár
    Footnotes
    * From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine.
    Affiliations
    St. Louis, Missouri
    Search for articles by this author
  • Author Footnotes
    * From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine.
    Frank Hertelendy
    Correspondence
    Reprint requests: Frank Hertelendy, PhD, DSc, Department of Obstetrics and Gynecology, St. Louis University Medical Center, 3635 Vista Ave. at Grand Blvd., P.O. Box 15250, St. Louis, MO 63110-0250.
    Footnotes
    * From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine.
    Affiliations
    St. Louis, Missouri
    Search for articles by this author
  • Author Footnotes
    * From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine.
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      Objective: With Nω-nitro-l-arginine, a potent inhibitor of nitric oxide synthesis, we tested the hypothesis that nitric oxide plays a functional role in the blunted pressor responsiveness seen during pregnancy.
      Study Design: A group of six pregnant rats were instrumented on the fourteenth day of gestation and studied on days 19 and 20, as well as 7 days post partum. Another group of six virgin rats were similarly prepared and used 5 days after surgery. Blood pressure and heart rate were monitored in conscious freely moving animals before and during the administration of drugs or placebo. Results were analyzed, by one-way repeated-measures analysis of variance, with Dunnett's t test, or by paired t test where applicable.
      Results: Basal mean arterial pressure and heart rate were 90.8 ± 3.0 mm Hg and 330 ± 6 beats/min in pregnant animals and 107.1 ± 3.2 mm Hg and 315 ± 7 beats/min in nonpregnant animals. Pressor responses to angiotensin II, vasopressin, and norepinephrine were attenuated in gravid animals. Infusion of Nω-nitro-l-arginine significantly and in a dose-dependent manner increased mean arterial pressure and reduced heart rate. These effects could be completely reversed by l-arginine administration. Changes in mean arterial pressure were higher during pregnancy as compared with postpartum values. Nω-nitro-l-arginine infusion potentiated pressor responses to all three vasopressors, resulting in dose-response curves that were significantly shifted to the left, making them virtually identical in pregnant and postpartum rats.
      Conclusion: Our data support the emerging view that nitric oxide plays a key role in the regulation of blood pressure during pregnancy.

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