Changes in cervical ripening in the rat during pregnancy: effect of a nitric oxide synthase inhibitor

OBJECTIVE: To characterize the effect of pregnancy and L-NAME, a nitric oxide synthase inhibitor, on cervical ripening in the rat. STUDY DESIGN: To determine the change in cervical ripening during gestation, nonpregnant and timed pregnant Charles River Sprague Dawley rats were sacrificed at various times and their cervices were isolated and suspended between two hooks in physiologic solution in a bath connected to a cervimeter that precisely stretches the cervical tissues in incremental steps of 0.1 mm at 1 minute intervals. This procedure produces force versus displacement curves. The slope of the regression line through the linear portion of the force curve is taken as a parameter of cervical extensibility or resistance to stretch. Increases or decreases in slopes are representative of rigid and soft cervices respectively. To determine the effect of L-NAME on cervical ripening, pregnant rats were sacrificed on day 21 following treatment for 3 or 9 days with either saline (control group) or L-NAMF 50 mg/d (I-NAME group) via osmotic minipumps implanted subcutaneously. RESULTS: Cervical resistance decreased during pregnancy compared to cervical tissue from nonpregnant animals. The resistance declined rapidly during the last 3 to 4 days of pregnancy to reach the lowest levels immediately prior to and during labor, then rose quickly within one day postpartum (Fig. A). Treatment with L-NAME at various times in gestation significantly increased cervical resistance, as measured on day 21 (Fig. B). CONCLUSIONS: Cervical resistance measurements during pregnancy reflect changes in collagen content and the progressive changes that occur to ripen the cervix. Nitric oxide appears to be important in the control of collagen content and cervical softening prior to labor.