Endothelium-dependent relaxation and angiotensin II sensitivity in experimental preeclampsia.
OBJECTIVE
We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat.


METHODS
Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine-mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N(G)-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR.


RESULTS
The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia.


CONCLUSIONS
Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.
Department of Obstetrics and Gynecology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands ; Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Anne Marijn
AM
van der Graaf
Marjon J
MJ
Wiegman
Torsten
T
Plösch
Gerda G
GG
Zeeman
Azuwerus
A
van Buiten
Robert H
RH
Henning
Hendrik
H
Buikema
Marijke M
MM
Faas
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014665:Vasodilator Agents; D000804:Angiotensin II; C073402:PD 123319; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019808:Losartan