Possible involvement of aminopeptidase A in hypertension in spontaneously hypertensive rats (SHRs) and change of refractoriness in response to angiotensin II in pregnant SHRs.
BACKGROUND
Hypertension complicated with pregnancy is a major cause of maternal and fetal mortality, but its pathophysiology is unclear.


OBJECTIVE
To investigate the pressor response to angiotensin II (Ang II) and the involvement of the Ang II degrading protease, aminopeptidase A, in spontaneously hypertensive rats (SHRs).


METHODS
Pregnant SHRs and Wistar-Kyoto (WKY) rats were studied. Angiotensin II (200 ng/kg per min) or saline was infused by osmotic pump from day of 15 gestation, and caesarean section was performed at day 20 of gestation. Blood pressure during pregnancy, weight of placentas and pups at caesarean section, and aminopeptidase A activity in placenta and renal cortex were measured.


RESULTS
Ang II treatment induced increases in blood pressure that were greater in non-pregnant WKY rats than those in pregnant WKY rats, pregnant SHRs, and non-pregnant SHRs. Renal aminopeptidase A activity in SHRs was significantly lower than that in WKY rats. Renal aminopeptidase A activity in pregnant SHRs was significantly greater than that in non-pregnant SHRs, but there was no significant increase in pregnant WKY rats. Placental aminopeptidase A activity in SHRs was greater than that in WKY rats. Placental aminopeptidase A activity in WKY rats was increased by Ang II, but was not increased in SHRs. Weights of placentas and pups were significantly lower in SHRs than in WKY rats.


CONCLUSIONS
Renal aminopeptidase A may be involved in the development of hypertension and the regulation of blood pressure in SHRs. Placental aminopeptidase A may be upregulated in response to fetal stress in pregnant SHRs.
Nakashima
Yutaka
Y
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ohno
Yasumasa
Y
Itakura
Atsuo
A
Takeuchi
Mikihito
M
Murata
Yasutaka
Y
Kuno
Naohiko
N
Mizutani
Shigehiko
S
D000626:Aminopeptidases / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D043384:Glutamyl Aminopeptidase; D006973:Hypertension / Q000378:metabolism*; D007672:Kidney Cortex / Q000201:enzymology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase