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Relaxation Kinetics of the Aorta in N-nitro-L-arginine Methyl Ester-Treated Pregnant Rats

Yuri P. Vedernikov, MD, PhD

George R. Saade, MD

Kristof Chawlisz, MD, PhD

Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas and Research Laboratories of Schering AG, Berlin, Germany

Robert E. Garfield, PhD

Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas and Research Laboratories of Schering AG, Berlin, Germany; Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, 301 University Boulevard, Route J-62, Galveston, TX 77555-1062; rgarfiel{at}marlin.utmb.edu

Objective: To test the hypothesis that vascular relaxation kinetics are prolonged in pregnant rats treated chronically with N-nitro-L-arginine methyl ester (L-NAME).

Methods: Timed pregnant rats (on day 13 of a 22-day gestation) were implanted with infusion pumps containing vehicle (controls) or L-NAME (50 mg/d). L-NAME pumps were retained until day 22 (group 1), or removed on day 20 (group 2). All rats were killed at term. Aortic rings were mounted in organ chambers containing physiologic salt solution (PSS) for isometric tension recording, contracted with high-K⁺ PSS (60 mM), and allowed to relax in normal-K⁺ PSS. Relaxation kinetics were quantified as time for 50% and 80% relaxation. After contraction with phenylephrime, responses to cumulative concentrations of methacholine were studied in the absence and presence of L-arginine (L-Arg) (10^-3 M).

Results: Responses to methacholine were inhibited completely in group 1 and partially in group 2 P < .05). The inhibition in both groups was reversed by L-Art. The rate of relaxation was significantly slower in groups 1 and 2 (P < .05) as compared with controls. Mechanical removal of the endothelium caused prolongation of relaxation in controls and group 2 (P < .05), but not in group 1. Preincubation of aortic rings from untreated control with L-NAME (in vitro, 10^-4 M) did not affect relaxation.

Conclusion: The endothelium medulates the are of vascular relaxation by a factor other than nitric oxide. N-nitro-L-arginine methyl ester (L-NAME) prolongs vasorelaxation by endothelium-dependent and -independent mechanisms. Prolongation of vascular relaxation kinetics may be a mechanism to elevate blood pressure and peripheral vascular resistance in preeclampsia.

Key Words: Aorta • endothelium • nitric oxide • preeclampsia • pregnant rat • relaxation kinetics

Journal of the Society for Gynecologic Investigation, Vol. 6, No. 1, 11-16 (1999)
DOI: 10.1177/107155769900600104


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