Effect of ovariectomy and hormone replacement therapy on small artery biomechanics in angiotensin-induced hypertension in rats

Objectives To test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depl eted state (proposed to increase cardiovascular vulnerability) and with hor mone replacement. Design Biomechanical properties of saphenous artery segments from ovariecto mized (n =10), ovariectomized + chronically angiotensin II infused-(n = 10) , and ovariectomized + chronically angiotensin II-infused + sex hormone-rep laced (n =10) rats were studied. Methods Surgical ovariectomy was performed. Osmotic minipumps were used for chronic angiotensin II infusion (100 ng/min per kg). For hormone replaceme nt therapy, oestradiol-propionate, 450 mug/kg for 7 days + medroxyprogester one-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 week s, cylindrical segments of the saphenous artery were prepared and subjected to in-vitro microarteriographic measurements. Pressure-diameter curves (0- 200 mmHg) were recorded in Krebs-Ringer solution, with smooth muscle contra cted (norepinephrine, 16 mu mol/l) and with relaxed (papaverine, 28 mu mol/ l). Results Chronic angiotensin II infusion significantly reduced the inner rad ius (at 100 mmHg: 298 +/- 17 mum versus 347 +/- 7 mum, P<0.001), while wall -thickness did not change. Hormone replacement restored the morphological r adius (333 +/- 7 <mu>m). Angiotensin II infusion slightly increased the ful l contraction range of the segments (defined as the percentage difference b etween fully contracted and fully relaxed diameters), which was further sig nificantly increased by hormone replacement (39 +/- 4% 46 +/- 8%, 62 +/- 7% at 100 mmHg, in the three groups, respectively; P<0.05). Despite unaltered stiffness in relaxed state, elastic moduli computed for the contracted seg ments decreased after hormone replacement. Conclusions These observations give further experimental support to the hyp othesis that sex hormone replacement might be useful in preventing the deve lopment and/or stabilization of postmenopausal hypertension, as well as in treating existing disease. J Hypertens 18:1587-1595 (C) 2000 Lippincott Wil liams & Wilkins.