The objective of these experiments is to test the hypothesis that ET-1 plays an important role in regulating maternal systemic arterial blood pressure, systemic vascular resistance, uterine and renal hemodynamics, as well as renal permeability to proteins in nonpregnant and pregnant ewes.
Aim 1 is to determine the dose of an ET-1 converting enzyme inhibitor required to block the conversion of big ET-1 to processed ET-1, and to determine if the endogenous production of ET-1 plays a role in modulating cardiovascular dynamics in pregnant and nonpregnant ewes.
Aim 2 is to determine the systemic, uterine, and renal vascular responses to both local and intravenous infusion of ET-1.
Aim 3 is to determine the mechanism by which the uterine artery becomes refractory to the vasoconstrictor actions of ET-1 during pregnancy.
Aim 4 is to test the hypothesis that infusions of ET-1 results in hypertension, reduced uterine blood flow, hemoconcentration, and proteinuria in both pregnant and nonpregnant sheep.
| Mershon, John L; Baker, R Scott; Clark, Kenneth E (2002) Estrogen increases iNOS expression in the ovine coronary artery. Am J Physiol Heart Circ Physiol 283:H1169-80 |
| McElvy, Sherrie; Greenberg, Suzanne; Baker, R Scott et al. (2002) Effect of Ro 61-1790, a selective endothelin-A receptor antagonist, on systemic and uterine hemodynamics and fetal oxygenation in sheep. Am J Obstet Gynecol 186:55-60 |
| McElvy, S; Greenberg, S G; Mershon, J L et al. (2001) Mechanism of uterine vascular refractoriness to endothelin-1 in pregnant sheep. Am J Physiol Heart Circ Physiol 281:H804-12 |
| Greenberg, S G; Clark, K E (1999) Hemodynamic effects of platelet-activating factor in nonpregnant and pregnant sheep. Am J Physiol 277:R996-R1001 |
| Greenberg, S G; Baker, R S; Yang, D et al. (1997) Effects of continuous infusion of endothelin-1 in pregnant sheep. Hypertension 30:1585-90 |
