Effects of combined sex hormone replacement therapy on small artery biomechanics in pharmacologically ovariectomized rats

Abstract

Objectives: The purpose of this study was to determine the effects of long-term combined sexual hormone replacement therapy on the biomechanical properties of the small artery wall in castrated female rats. Methods: 30 non-pregnant mature female Sprague–Dawley rats were pharmacologically ovariectomized with 750 μg/kg triptorelin im. every 4th week. Ten of them received combined hormone replacement in form of 15 mg/kg medroxyprogesterone acetate (MPA) im. every 2 weeks and 450 μg/kg estradiol propionate im. once a week. Ten castrated animals received MPA only. Ten control, castrated animals were given the vehicles of these steroids. Ten other animals were kept parallelly, receiving the vehicles of all drugs (control animals). After 12 weeks of treatment cylindrical segments of the saphenous artery were isolated and cannulated at both ends and subjected to in vitro microarteriographic test. Pressure–diameter curves, in the range of 0–200 mmHg, were recorded from segments in normal Krebs–Ringer (nKR) solution, in contraction with norepinephrine (1.6×10 −5 M), and then in relaxation with papaverine (2.8×10 −5 M). Biomechanical parameters were calculated based on the pressure–diameter curves. Results: Combined hormone replacement therapy significantly increased the passive diameter of small arteries, as compared to those from ovariectomized animals without hormone replacement. MPA monotherapy did not alter the vessel diameter, the inner radii at 100 mmHg intraluminal pressure were, 300±9 μm in the control castrated, 340±7 μm in the estradiol+MPA replaced and 306±8 μm in the MPA treated groups ( P<0.05 between the control castrated and the combined treatment groups). The vascular reactivity to norepinephrine or papaverine was not changed significantly either by combined hormone replacement or by MPA monotherapy when compared with ovariectomized controls. No significant alterations were found in wall thickness and distensibility. Conclusions: These results suggest that chronic medroxyprogesterone pretreatment does not influence the geometric, elastic and contractile properties of small arteries in castrated female rats. The combination of MPA+estradiol increased the morphological lumen: the morphological vasodilatation induced by estrogen, described earlier, was not affected by the addition of this progestin to the regimen.