Effects of oestrogen treatment and angiotensin-converting enzyme inhibition on the microvasculature of ovariectomized spontaneously hypertensive rats.
We investigated the role of oestrogen in the function and structure of the microcirculation of female spontaneously hypertensive rats (SHRs), and evaluated the effect of 17beta-oestradiol on their cardiovascular response to pharmacological agents that block the formation of angiotensin II. Ten-week-old SHRs were randomly assigned to the following groups: intact, ovariectomized, and ovariectomized treated with 17beta-oestradiol (1.5 mg delivered over 60 days) and/or captopril (5 mg kg(-1) day(-1) for 8 weeks). Systolic blood pressure was determined from the time of ovariectomy up to 18 weeks of age, at which time endothelial function and microvascular density in skeletal muscle were evaluated. Both 17beta-oestradiol and captopril prevented development of hypertension in ovariectomized rats. Furthermore, coadministration of both drugs had a greater antihypertensive effect than either one alone. Acetylcholine-induced vasodilatation was impaired in ovariectomized SHRs, and the response was improved by treatment with 17beta-oestradiol and/or captopril. In addition, 17beta-oestradiol replacement in ovariectomized rats enhanced the effect of captopril on acetylcholine-induced vasodilatation. Ovariectomized rats also showed lower microvascular density than intact rats, an effect that was prevented by 17beta-oestradiol replacement or captopril treatment and, to a significantly larger extent, by coadministration of both. We concluded that both 17beta-oestradiol and captopril attenuated the development of hypertension and improved the impairment in microvascular density of ovariectomized SHRs. Moreover, when simultaneously administered, oestradiol and captopril had an additive effect on blood pressure and the microvasculature.
Giménez
Jose
J
Departament of Physiology, Facultad de Medicina, Universidad de Murcia, Spain.
Garcia
Paz M
PM
Bonacasa
Barbara
B
Carbonell
Luis F
LF
Quesada
Tomas
T
Hernández
Isabel
I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000517:prevention & control; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004967:Estrogens; D004958:Estradiol; D002216:Captopril