Effect of estrogen and angiotensin-converting enzyme inhibitor on vascular remodeling in ovariectomized spontaneously hypertensive rats.
OBJECTIVE
The present study evaluated whether estrogen influences the effect of angiotensin-converting enzyme inhibition in preventing the vascular remodeling induced by hypertension and also investigated the signal mechanism involved in that effect.


METHODS
Ten-week-old female spontaneously hypertensive rats were ovariectomized (OVX) and randomly assigned to the groups: untreated OVX and treated with 17beta-estradiol (estradiol, 1.5 mg) and/or captopril (5 mg/kg/day). Evolution of systolic blood pressure was determined until 18 weeks. At that time, the heart and mesentery were excised. Structural changes in coronary vessels were quantified by an image analyzer. Inmunoblotting was performed on mesenteric arteries for determination of phosphorylated (ERK1/2).


RESULTS
Estradiol treatment enhanced the antihypertensive effect of captopril in OVX rats. Treatment with captopril slightly modified the media cross-sectional area and wall-to-lumen of myocardial arterioles from OVX spontaneously hypertensive rats, whereas coadministration of captopril and estradiol significantly reduced the media cross-sectional area, wall-to-lumen ratio, and perivascular fibrosis in OVX spontaneously hypertensive rats. Captopril alone did not significantly inhibit extracellular signal-regulated kinase 1/2 phosphorylation, whereas coadministration of captopril and estradiol significantly attenuated this parameter.


CONCLUSIONS
These results indicate that estrogen may enhance the angiotensin-converting enzyme inhibition-mediated improvement of vascular remodeling in hypertension, which may be partly mediated via inhibition of extracellular signal-regulated kinase 1/2.
García
Maria P
MP
Department of Physiology, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Giménez
Jose
J
Serna
Mar
M
Salom
Miguel G
MG
Bonacasa
Bárbara
B
Carbonell
Luis F
LF
Quesada
Tomas
T
Hernández
Isabel
I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004958:Estradiol; D002216:Captopril