Viagra shows selective effects in hypertensive pregnancy on mother, fetus

Possible therapeutic role in preeclampsia, the leading cause of worldwide maternal mortality, illness

San Diego (April 3, 2005) – The first study to consider the effect of Viagra (sildenafil) during pregnancy affected by hypertension on such significant facts as fetal growth and well-being and the mother's uterine circulation yielded surprisingly positive results, which may indicate possible utility in preeclampsia, the leading cause of maternal mortality and morbidity worldwide.

Although Viagra didn't actually lower mothers' blood pressure, "it did produce some very significant and beneficial effects on pregnancy-induced vascular adaptation and fetal outcome," according to senior author/laboratory head, George Osol, professor and director of research, Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington.

*Paper presentation: "Beneficial effects of Viagra on fetal and vascular parameters in hypertensive pregnancy in the rat," 12:30 p.m.-3 p.m. Tuesday April 5, Physiology 909.9/board #A134. On view 7:30 a.m. - 4 p.m.

Research was performed by George Osol, Gerard Celia and Natalia I. Gokina, Department of Obstetrics and Gynecology, University of Vermont College of Medicine, with the assistance of lab technician Keara McElroy-Yaggy.

Osol and his team are presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.

Osol said that when given to pregnant rats with induced hypertension, Viagra:

1. Helped arteries of the uterus grow as they should during pregnancy. "Hypertension decreases the growth and alters contractility of blood vessels in the uterus," Osol said, "but giving Viagra reversed these effects, resulting in improved function of the uterine circulation." Arterial diameters of Viagra-treated animals didn't quite match control (normal) values, "but were significantly larger than those with hypertension, suggesting that it may have increased blood flow to the uterus and placenta," Osol added.

2. Increased fetal weights to normal values, compared with untreated hypertensive offspring whose weights were reduced by more than 20%. "This observation also supports an effect on uterine blood flow since it well known that restriction of uterine blood flow during pregnancy is associated with reduced fetal weight, which is a serious clinical problem," Osol added.

3. "Third, and most surprisingly, Viagra completely prevented fetal resorption, or fetal mortality. Whereas 11% (6/52) of fetuses were lost in the hypertensive group, none were lost in the group that received Viagra, even though they were still hypertensive," Osol said.

Selective effect of Viagra in pregnancy/hypertension called intriguing, "preliminary"

Urging caution, Osol noted that further study is needed to better understand how and why Viagra aids maternal uterine vascular adaptation and fetal health; whether similar benefits will occur in humans and whether there might be any harmful effects.

Nevertheless, Osol said the findings being reported "are exciting because they suggest that Viagra (or other drugs that inhibit PDE-5, the enzyme that normally inhibits blood vessels' ability to expand) may have beneficial effects in hypertensive pregnancy and, possibly, preeclampsia. It is also intriguing that the benefits of Viagra were observed without any reduction in maternal blood pressure, thereby dissociating hypertension per se from the loss of NO (nitrous oxide) signaling in the uterine circulation."

Avoiding current antihypertensive therapy complications in pregnancy?

Osol pointed out that "this is an important distinction, because it demonstrates a selective effect of Viagra on the uteroplacental circulation and avoids some of the complications of antihypertensive therapy during pregnancy, particularly the danger of reducing uteroplacental blood flow (placental underperfusion) secondary to the reduction of systemic blood pressure."

Hypertensive pregnancy develops in about 10% of women, disrupting normal vascular adaptation. During normal pregnancy, arteries that supply the uterus with blood enlarge, allowing uterine blood flow to increase more than 10-fold in humans, facilitating nourishment of the fetus and ensuring sufficient blood supply to the uterus during labor. This vascular adaptation during pregnancy is characteristic of mammals, including humans, sheep, pigs and rats.

Next steps. Based on these provocative results, future studies will evaluate the effects of Viagra on uterine blood flow changes during pregnancy, and "possible changes in other systems that contribute to normal fetal growth and development, such as placental transport and immune function," Osol said.