The hypothesis to be tested in this proposal is that there is a reduction in vascular reactivity to norepinephrine in the mesenteric arteries of the pregnant rat which is composed of both specific sensitivity changes to norepinephrine and alterations in the contractile properties of the vasculature. This hypothesis will be tested by examining certain mechanical and morphological properties of small mesenteric arteries (less than 200 Mu) from rats at three stages of gestation. This size artery has been shown to play a significant role in blood pressure regulation in the rat. Using light and electron microscopy in conjunction with a specially designed in vitro myograph system, some basic mechanical properties will be determined including active and passive tension-internal circumference relationships and maximal active wall and smooth muscle stresses. The sensitivity to norepinephrine will also be measured at the different stages of gestation by generating dose-response curves. The appropriate agonists and antagonists will be used to assess the contributions that intra-and extraneuronal uptake mechanisms might make to changes in norepinephrine sensitivity during pregnancy. The long term objective of this research is to further our understanding of the mechanisms by which vascular reactivity is altered during pregnancy in the human and how these relate to the clinical syndrome of pregnancy-induced hypertension. This proposal will provide basic information regarding two major components of vascular reactivity, contractility and sensitivity, as they relate to norepinephrine mediated contractile activity of the pregnant rat mesenteric circulation. This is the first attempt to determine these mechanical and contractile properties in this size mesenteric vessel during pregnancy. It is hoped that such information can ultimately be applied to investigating similar changes in the human.
