Antihypertensive effects of flutamide in rats that are exposed to a low-protein diet in utero.
OBJECTIVE
We investigated whether gestational age of in utero low-protein diet played a role in the subsequent development of adult hypertension and whether it is gender dependent and examined whether flutamide (a specific, nonsteroidal competitive antagonist of the androgen receptor) reduces blood pressure in rat offspring that are exposed to in utero low-protein diet (6%).


METHODS
Pregnant rats were fed either with 20% protein (control) or 6% protein (low-protein diet) from day 1 or day 12 of gestation. Fetoplacental weights and mortality rates of pups were assessed. Systolic blood pressure, mean arterial blood pressure, and circulatory hormone levels in offspring were determined. In addition, male and female hypertensive offspring were treated with flutamide, and their blood pressure was monitored.


RESULTS
After delivery, pup weights were reduced, and pup mortality rates increased in the low-protein diet-day 1 group. Systolic blood pressure and mean arterial blood pressure were elevated in low-protein diet-day 1 males and females and low-protein diet-day 2 males. Significant (P < .05) reduction in blood pressure was achieved with flutamide in low-protein diet-day 1 females. Serum estradiol levels were decreased (P < .05) in low-protein diet-day 1 females; flutamide attenuated this effect.


CONCLUSIONS
The day of in utero insult by low-protein diet is critical in the induction of adult hypertension; the severity is gender dependent. Flutamide was found to protect against hypertension only in females.
Gangula
Pandu R R
PR
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-1062, USA.
Reed
Luckey
L
Yallampalli
Chandrasekhar
C
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018753:Diet, Protein-Restricted; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D005865:Gestational Age; D012739:Gonadal Steroid Hormones / Q000097:blood; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D000959:Antihypertensive Agents; D012739:Gonadal Steroid Hormones; D005485:Flutamide