This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.During pregnancy, blood flow to the uterus (womb) and placenta must increase a lot to support a normal pregnancy. This is accomplished by a combination of blood vessel growth, the creation of new blood vessels, and an increased ability of existing blood vessels to open up. Several diseases of pregnancy such as preeclampsia (toxemia) and fetal growth restriction are associated with insufficient uterine blood flow, and there are no current therapies that can selectively improved uterine blood flow. In particular, there are no drugs that will increase blood flow to the uterus only; as most drugs that increase blood flow are relatively nonspecific and result in widespread increase in blood flow to all organs that ultimately results in a vascular redistribution that reduces blood flow to the uterus. Sildenafil (Viagra) has been used to increase blood flow to the penis in men (hence its use in improving erectile dysfunction). Its relative specificity derives from its ability to inhibit an enzyme, phosphodiesterase 5 (PDE5), which is not present everywhere in the body, but has been localized in the blood vessels of the reproductive organs, and in the vessels of the lung. The latter effect has been recognized as a potential therapy for pulmonary hypertension. Several recent studies have shown that sildenafil is also able to induce dilation of arteries isolated from the human uterus (see references, below), although it's hemodynamic effects on uterine blood flow have yet to be defined. The purpose of this study is to definitively answer this question by measuring uterine blood flow in nonpregnant women with transvaginal ultrasound. If a significant and specific effect is observed, we will consider extending these studies to women who are pregnant and, eventually, to those that have clinically significant reductions in uterine blood flow as are sometimes evident in preeclamptics. The pilot protocol will involve recruiting 30 nonpregnant women, 2/3 of whom will receive Sildenafil (split evenly among 2 different standard clinical doses), and 1/3 of whom will receive no medication is a manner that is blinded to the clinical investigator.
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