Progesterone increases blood pressure in spontaneous gestational hypertension in rats.
BACKGROUND
Gestational hypertensive disorders are a leading cause of maternal mortality in the US, accounting for up to 10% of these deaths. During pregnancy, a new rat model (SHHF rat) has been shown to develop spontaneous hypertension with increases of more than 40 mm Hg systolic blood pressure (BP), which resolves after delivery, and which lead us to ask whether the hypertension may be triggered by increased levels of progesterone in these rats.


METHODS
To test this hypothesis, groups of SHHF rats were treated with progesterone (PROG), estrogen (EST), or progesterone and estrogen (PROG+EST) that correspond to levels that occur during pregnancy. Control (CON) rats received saline-filled implants and pseudopregnancy was induced in another group. Wistar-Kyoto rats served as controls for SHHF rats.


RESULTS
By experimental day 3, progesterone caused a significantly higher systolic BP, similar to pseudopregnancy and to previously reported values during pregnancy in this strain. Blood pressure in SHHF rats given estrogen was not significantly different. RU486 reversibly prevented the increase in BP induced by progesterone.


CONCLUSIONS
These results indicate that an anomalous response to progesterone causes dramatic increases in BP in SHHF rats during a short period of time, in contrast to the decrease in BP in response to progesterone, which has been reported in other rat models of hypertension. An abnormal pressor response to progesterone should be considered a potential mechanism contributing to the development of hypertension during pregnancy.
Sharkey
Leslie C
LC
Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts, USA.
Kirchain
Sharon
S
McCune
Sylvia A
SA
Simpson
Gregory I C
GI
Archambault
Elizabeth Z
EZ
Boatright
Naomi K
NK
Hicks
Erin
E
Fray
John
J
D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013599:Systole / Q000187:drug effects
D004967:Estrogens; D015735:Mifepristone; D011374:Progesterone; D003404:Creatinine; D001219:Aspartate Aminotransferases