Preeclampsia remains a major cause of morbidity and mortality to both mother and unborn child. One reason for this the paucity of information concerning the control of normal blood pressure during pregnancy, as well as why peripheral vascular resistance increases so markedly in preeclampsia. Proposed is a study of morphological and contractile properties of omental resistance arteries obtained from pregnant normotensive women and patients with preeclampsia undergoing cesarian deliveries, comparing results to those from nongravid subjects undergoing laparotomy and gravidas with chronic hypertension. Properties of these 200 micromole arteries will be studied under isometric conditions in vitro, testing the following major hypotheses: 1.) Vasoconstriction induced by angiotensin II, vasopressin, and catecholamines will be attenuated in normal pregnancy, but augmented in preeclampsia; these alterations due primarily to altered basal release of endothelium-derived vasodilator substances (e.g., EDRF). 2.) Relaxation of resistance vessels induced by endothelium dependent vasodilators will be enhanced in normal pregnancy but impaired in preeclampsia. 3.) Spontaneous relaxation of vessels after washout of vasoconstrictors will be delayed in preeclampsia, and 4.) There will be increased expression of message for NO synthase in normal pregnancy which will be reduced in preeclampsia. Vasoconstrictor responses, induced by above noted agonists, will be compared in endothelium-intact and -denuded vessels from each group with similar comparisons following inhibition of EDRF synthesis with nitroarginine. As well, several inhibitors will be used to determine if eicosanoids or novel endothelial factors play a role in our observations. Also, endothelium- dependent and independent vascular relaxation will be compared between groups and a newly-developed competitive PCR method will be applied to quantitate the mRNA for constitutive and inducible nitric oxide synthases in these microvascular tissues. Finally whether or not any findings are due to structural changes in these vessels, will be determined in part by comparing data from preeclamptics with those from chronic hypertensives. The choice of vessels from humans reflects the fact that as yet there are no convincing animal models of preeclampsia. The focus on resistance arteries is because they are the major determinants of blood pressure. Information from these experiments should enhance our understanding of preeclampsia, and eventually lead to better methods of predicting, preventing, and managing this malicious disease.
