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

Abstract

OBJECTIVES:

To test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depleted state (proposed to increase cardiovascular vulnerability) and with hormone replacement.

DESIGN:

Biomechanical properties of saphenous artery segments from ovariectomized (n = 10), ovariectomized + chronically angiotensin II infused-(n = 10), and ovariectomized + chronically angiotensin II-infused + sex hormone-replaced (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 replacement therapy, oestradiol-propionate, 450 microg/kg for 7 days + medroxyprogesterone-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 weeks, 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 contracted (norepinephrine, 16 micromol/l) and with relaxed (papaverine, 28 micromol/l).

RESULTS:

Chronic angiotensin II infusion significantly reduced the inner radius (at 100 mmHg: 298 +/- 17 microm versus 347 +/- 7 microm, P< 0.001), while wall-thickness did not change. Hormone replacement restored the morphological radius (333 +/- 7 microm). Angiotensin II infusion slightly increased the full contraction range of the segments (defined as the percentage difference between fully contracted and fully relaxed diameters), which was further significantly 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 segments decreased after hormone replacement.

CONCLUSIONS:

These observations give further experimental support to the hypothesis that sex hormone replacement might be useful in preventing the development and/or stabilization of postmenopausal hypertension, as well as in treating existing disease.

• Authors: S Várbíró, G L Nádasy, E Monos, Z Vajó, N Acs, Z Miklós, A M Tökés, B Székács
• Journal: Journal of hypertension (J Hypertens) Vol. 18 Issue 11 Pg. 1587-95 (Nov 2000) ISSN: 0263-6352 [Print] Netherlands
• PMID: 11081771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Progesterone Congeners
• Vasoconstrictor Agents
• Angiotensin II
• Estradiol
• Medroxyprogesterone Acetate

Topics

• Angiotensin II (pharmacology)
• Animals
• Arterioles (drug effects, physiology)
• Blood Pressure (drug effects, physiology)
• Elasticity
• Estradiol (pharmacology)
• Female
• Hormone Replacement Therapy
• Hypertension (chemically induced, drug therapy)
• Medroxyprogesterone Acetate (pharmacology)
• Menopause
• Ovariectomy
• Progesterone Congeners (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vascular Resistance (drug effects, physiology)
• Vasoconstriction (drug effects, physiology)
• Vasoconstrictor Agents (pharmacology)
• Weight Gain