Stephen Marx

Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix.

This study examines the relationship between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the control of cervical ripening and parturition under normal (normal term pregnancy) and abnormal (preterm labor and prolongation of pregnancy) conditions by (a) measuring changes in the collagen both visually and quantitatively, (b) localizing and characterizing iNOS and COX-2 under normal conditions, and (c) characterizing the changes in iNOS and COX-2 under abnormal conditions. Cervices are obtained from estrus and timed pregnant Sprague-Dawley rats (n=4-10 per group). Preterm labor is induced with Onapristone (3 mg/rat; progesterone antagonist) and the prolongation of pregnancy with progesterone (2.5 mg, twice daily). Collagen changes are measured and visualized with the picrosirius polarization method. RT-PCR is used to characterize the mRNA expression (p<0.5), and immunohistochemistry is used to localize the protein expression for iNOS and COX-2. The organization and birefringence of the collagen during pregnancy decreased and is supported by changes in the luminosity (p<0.001). The iNOS and COX-2 enzymes were localized in cervical smooth muscle, vascular smooth muscle, and epithelium. Under normal conditions, iNOS mRNA levels decreased as COX-2 mRNA levels increased demonstrating an inverse correlation (Spearman r = −0.497; p=0.00295). Onapristone stimulated preterm labor, increasing the iNOS and COX-2 mRNA (p<0.05). The increase demonstrated a positive correlation (Spearman r = 0.456; p=0.03). Progesterone prolonged pregnancy, decreasing the iNOS and COX-2 mRNA (p=0.036). In conclusion, there may be an interaction between the nitric oxide and prostaglandin pathways in cervical ripening and parturition.

Neurokinin B peptide serum levels are higher in normotensive pregnant women than in preeclamptic pregnant women.

OBJECTIVES The purpose of this study was to examine neurokinin B levels in serum from preeclamptic and normotensive and to investigate the role of neurokinin B in preeclampsia. STUDY DESIGN Peripheral and uterine venous blood neurokinin B levels were measured in 14 normotensive and 8 preeclamptic pregnant women by radioimmunoassay. RESULTS Neurokinin B levels in normotensive women were 4.91 +/- 2.67 nmol/L in peripheral and 5.59 +/- 2.06 nmol/L in uterine blood. In pregnant women with preeclampsia, neurokinin B levels were 2.79 +/- 1.68 nmol/L and 3.20 +/- 1.55 nmol/L, respectively. Neurokinin B levels were significantly higher in normotensive women (P=.032 in peripheral and P=.006 in uterine blood). CONCLUSIONS Neurokinin B serum levels were higher in normotensive women. Higher neurokinin B concentrations in normotensive pregnant women may be due to the advanced gestational age and/or the result of a negative interaction of other vasoactive substances. The role of neurokinin B in preeclampsia remains to be determined.

Citrulline does not relax isolated rat and rabbit vessels.

The study was prompted by the report of Ruiz E. & Tejerina T., 1998 describing endothelium‐independent relaxation by L‐citrulline via activation of particulate guanylate cyclase. We compared the effects of L‐citrulline and L‐arginine in isolated aortic rings of rats and in isolated aortic, carotid and femoral artery rings of rabbits. No significant relaxation to either L‐citrulline or L‐arginine was found in the concentration range of 10−12 to 10−3 M, while 3‐morpholinosydnonimine hydrochloride (SIN‐1, 10−6 M) relaxed vascular tissues. This study does not support the conclusion that L‐citrulline has direct vasorelaxing action on vascular smooth muscle.

Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide-induced, but not antiprogestin-induced, preterm cervical ripening in timed-pregnant rats.

OBJECTIVE The purpose of this study was to determine whether the platelet-activating factor antagonist WEB-2170 inhibits preterm cervical ripening induced by lipopolysaccharide or by antiprogestin RU 486. STUDY DESIGN Timed-pregnant rats were killed on day 16 after treatment with (1) WEB-2170, lipopolysaccharide, lipopolysaccharide plus WEB-2170, or vehicle control and (2) with WEB-2170, RU 486, RU 486 plus WEB-2170, or vehicle control. Cervical ripening was assessed by light-induced fluorescence and resistance to stretch. Statistics were assessed by 1-way analysis of variance followed by Tukey-test (P <.05). RESULTS Light-induced fluorescence and resistance to stretch were significantly lower in the lipopolysaccharide-treated and in the RU486-treated animals compared with vehicle control (lipopolysaccharide:light-induced fluorescence, 7.0+/-0.6 vs 12.8+/-0.8 [P=.001]; resistance to stretch, 0.41+/-0.03 N/mm vs 0.54+/-0.04 N/mm [P <.05]; RU486:light-induced fluorescence, 9.6+/-0.6 vs 11.7+/-0.6 [P <.05]; resistance to stretch, 0.28+/-0.06 N/mm vs 0.61+/-0.02 N/mm [P <.001]). Compared with vehicle control, WEB-2170 alone did not alter cervical light-induced fluorescence or resistance to stretch. Although WEB-2170 significantly blocked cervical ripening after lipopolysaccharide administration (light-induced fluorescence, 11.3+/-1.3 [P <.05]; resistance to stretch, 0.61+/-0.04 [P <.01]), WEB-2170 did not inhibit the RU 486-induced cervical ripening. CONCLUSION Although infection-related cervical ripening is inhibited by platelet-activating factor antagonists, the physiologic process of cervical ripening appears to be unaffected. Platelet-activating factor inhibition may be of clinical value in the infection-related pathologic processes that are responsible for premature cervical ripening.