17Beta-oestradiol enhances the acute hypotensive effect of captopril in female ovariectomized spontaneously hypertensive rats.
The objective of this study was to investigate whether the acute haemodynamic effects of angiotensin-converting enzyme inhibition with captopril could be enhanced by oestrogen administration, and then to evaluate the mechanisms involved in this enhancement. All experiments were performed in 18-week-old female spontaneously hypertensive rats arranged in three experimental groups: intact; ovariectomized (OVX); and ovariectomized plus treatment with 17beta-oestradiol (OVX + E2). These groups were used to evaluate the effects of captopril administration alone, or following bradykinin B2 receptor blockade or nitric oxide synthase inhibition, on a number of haemodynamic parameters (mean arterial pressure, cardiac index, vascular resistance and heart rate). The drop in mean arterial pressure and vascular resistance index in response to captopril was more pronounced in intact and ovariectomized rats treated with 17beta-oestradiol than in ovariectomized animals. Blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis attenuated the synergy between 17beta-oestradiol and captopril. It is concluded that ovariectomy blunted the blood pressure and vascular resistance index drop observed in intact rats in response to captopril. Treatment with 17beta-oestradiol prevented the blunted response to captopril in ovariectomized rats. Kinins and nitric oxide may be involved in the mechanisms of 17beta-oestradiol potentiation of the haemodynamic effects of captopril.
Giménez
José
J
Department of Physiology, Faculty of Medicine, University of Murcia, Murcia, Spain.
García
M Paz
MP
Serna
Mar
M
Bonacasa
Bárbara
B
Carbonell
Luis F
LF
Quesada
Tomás
T
Hernández
Isabel
I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage*; D004338:Drug Combinations; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004338:Drug Combinations; D004958:Estradiol; D002216:Captopril