Endocrine Abstracts

Introduction: Selective oestrogen receptor modulators function as oestrogen receptor antagonist in the breast and gonads, while they have agonistic effects on the bone and the cardiovascular system. It is also known that endogenously produced carbon monoxide by the heme-oxigenase (HO) enzyme exerts beneficial actions in cardiovascular protection.

Design: Intact females, ovariectomized (OVX), raloxifene or oestrogen treated OVX Wistar rats were used. We studied i) the activity and expression of HO enzymes in the left ventricle (LV) and aorta ii) the ST segment depression (standard lead II surface ECG) provoked by the administration of adrenaline (1 μg/kg, i.v.) and 30 second later phentolamine (1 mg/kg, i.v.), iii) the increase of blood pressure in vivo and iv) heart perfusion ex vivo induced by arginine vasopressine (AVP).

Results: We found that OVX i) decreased in the LV HO activity (from 2.65±0.29 to 0.78±0.12 nmol bilirubin/h per milligram protein; n=9–10; P<0.05) and HO-2/HO-1 expression (HO-2: from 93.14±1.79 to 48.0±2.76%; HO-1: from 87.43±3.02 to 39.86±4.79%; n=10; P<0.05) and in the aorta (HO activity from 6.72±0.44 to 3.56X±0.31 nmol bilirubin/h/mg protein; n=8–10; P<0.05; HO-2: from 92.25±2.03 to 56.51±3.24%; HO-1: from 83.80±3.30 to 57.47±2.32%; n=12; P<0.05), ii) increased the susceptibility of the heart towards ischemia (ST segment depression: from −0.011±0.025 to −0.13±0.037 mV; n=10; P<0.05), iii) increased the response of blood pressure and iv) decreased the heart perfusion to AVP. The oestrogen and raloxifene replacement restored the differences to the level observed in the ovary-intact females. Finally, HO inhibition by tin-protoporphyrine pre-treatment augmented the response of blood pressure, the ST depression and heart perfusion in all groups investigated.

Conclusion: Oestrogen improves cardiovascular defence in menopause, at least in part, by a HO-mediated pathway. In our system, raloxifene exerts oestrogen agonistic effect.

Grant supports: SROP 4.2.1./B-09-1/KNOV-210-0005; SROP 4.2.2.-08/1-2008-0006; Bolyai Scholarship (Aniko Posa).