The effects of the menopause and hormone replacement therapy on small artery contractility are poorly understood. In this study we investigated the responsiveness to agonist stimulation of subcutaneous resistance arteries (150Ð250 mm diameter), obtained from gluteal biopsies taken (under lignocaine anaesthesia) from four volunteer groups of women: pre-menopausal (pre-mw) (n = 11), post-menopausal (post-mw) (n = 17), post-menopausal receiving oestrogen replacement therapy (post-mw + ERT) (n = 8) and post-menopausal women receiving combined oestrogen and progestin replacement therapy (post-mw + HRT) (n = 7). Approval was obtained from the Central Manchester Healthcare Trust Ethical Committee.
Isolated arteries were mounted on a pressure myograph (at 30 mmHg) and superfused with physiological salt solution (pH 7.4, 37 °C). All data are expressed as means ± S.E.M. with differences between groups being tested for by Student’s unpaired t test.
All arteries exhibited concentration-dependent constrictor responses to phenylephrine (PHE), although those obtained from post-mw were significantly more sensitive compared with those from pre-mw (EC50 values = 4.16 X 10-8 ± 4.08 X 10-9 M and 8.83 X 10-8 ± 1.55 X 10-8 M, respectively (P < 0.05)). Arteries taken from post-mw + ERT had EC50 values similar to those observed in vessels from post-mw (7.91 X 10-8 ± 1.61 X 10-8 M) while those taken from post-mw + HRT had sensitivities which were intermediate between those of pre-and post-menopausal samples: 4.96 X 10-8 ± 1.16 X 10-8 M. Maximal responses to PHE were similar in all groups.
Both maximum responses and sensitivities to acetylcholine (ACh) were similar in arteries from all groups (75 ± 7 mm and 1.45 X 10-8 ± 4.38 X 10-9 M for pre-mw, 79 ± 7 mm and 9.87 X 10-9 ± 5.88 X 10-9 M for post-mw, 82 ± 6 mm and 1.59 X 10-8 ± 1.06 X 10-8 M for post-mw + ERT, and 89 ± 2 mm and 3.89 X 10-9 ± 1.17 X 10-9 M for post-mw + HRT). The presence of L-NNA (to inhibit nitric oxide synthase) reduced the maximal responses in arteries from pre-mw by 66.6 ± 8.9 %, from post-mw + ERT by 70.8 ± 8.0 % and from post-mw + HRT by 66.1 ± 9.6 %. Responses of arteries from post-menopausal women were, however, not altered by the inhibitor (101 ± 10 %). EC50 values were not significantly affected by L-NNA. Vasodilatory responses to sodium nitroprusside were similar in tissues from pre- and post-menopausal women.
These results suggest that sensitivity of isolated subcutaneous small arteries to PHE is enhanced in post-mw compared with pre-mw. Responses to ACh are unaffected by the menopause although the relative contribution of nitric oxide appears altered. These changes may be reversed by ERT and fully (ACh) or partially (PHE) reversed by HRT.
All procedures accord with current local guidelines.