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Effect of estrogen replacement therapy on blood pressure, renin-angiotensin system, and intracellular electrolytes
260A
POSTERS: Women’s Health
AJH–April 2001–VOL. 14, NO. 4, PART 2
P-687 EFFECT OF ESTROGEN REPLACEMENT THERAPY ON BLOOD PRESSURE, RENIN-ANGIOTENSIN SYSTEM, AND INTRACELLULAR ELECTROLYTES Marı´a Queralt Cardona, Marı´a Mongay, Alejandro de la Sierra. 1 Hypertension Unit, Hospital Clinic, Barcelona, Spain The aim of the study was to evaluate the effect of estrogen replacement therapy (ERT) on blood pressure (BP) assessed by both office and by 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we studied variations in biochemical and hormonal parameters that may represent possible mechanisms responsible for the BP effect. Thirty-five postmenopausal (mean age : 55 ⫾ 4 years) stage I hypertensive women not receiving antihypertensive treatment were studied. Patients were randomized to ERT (estradiol 50 mg plus medroxyprogesterone 5 mg) or no treatment (control group) for a 12-week period. At both baseline and at the end of treatment period we measured BP in the office and by 24-hour ABPM, biochemical parameters, plasma renin activity (PRA), plasma aldosterone and norepinephrine, as well as intraerythrocyte sodium concentration [Nai] and intraplatelet free calcium concentration [Cai]. The main results showed that ERT significantly (*p⬍0.05) decreased 24-hour, but not office systolic and diastolic BP. ERT also decreased plasma aldosterone levels and intraerythrocyte sodium concentration. In conclusion, treatment with ERT in hypertensive postmenopausal women significantly decreases BP, assessed by 24-hour ABPM. A decrease in RAS activity and in intracellular sodium concentration may represent possible responsible mechanisms Parameter
ERT (Nⴝ18) Baseline 12-week
Control (Nⴝ17) Baseline 12-week
Office SBP 165.9 ⫾ 14.3 162.5 ⫾ 15.9 164.9 ⫾ 13.3 165.8 ⫾ 19.4 Office DBP 97.1 ⫾ 6.8 95.1 ⫾ 7.4 96.4 ⫾ 5.4 95.6 ⫾ 7.4 24-h SBP 139.1 ⫾ 11.6 133.3 ⫾ 11.3* 141.6 ⫾ 16.7 144.6 ⫾ 17.9 24h DBP 86.2 ⫾ 8.2 82.2 ⫾ 8.6* 85.8 ⫾ 6.3 87.1 ⫾ 6.1 PRA (ng/mL/h) 0.21 ⫾ 0.15 0.17 ⫾ 0.14 0.11 ⫾ 0.07 0.15 ⫾ 0.18 Aldosterone (ng/dL) 14.8 ⫾ 9.1 10.6 ⫾ 6.4* 11.7 ⫾ 5.5 15.1 ⫾ 7.9 Norepinephrine 270 ⫾ 112 397 ⫾ 205 306 ⫾ 195 335 ⫾ 125 (pg/mL) [Nai] (mmol/L) 9.4 ⫾ 1.6 8.3 ⫾ 1.2* 8.7 ⫾ 1.1 9.0 ⫾ 1.4 [Cai] (nmol/L) 29.3 ⫾ 4.8 30.5 ⫾ 4.5 30.5 ⫾ 9.4 31.3 ⫾ 4.2
Key Words: Intracellular Electrolytes, Estrogen Replacement Therapy, Ambulatory Blood Pressure Monitoring
P-688 PROGESTERONE IMPROVES MEMBRANE FUNCTION OF ERYTHROCYTES BY THE NITRIC OXIDE-DEPENDENT MECHANISM -AN ELECTRON PARAMAGNETIC RESONANCE INVESTIGATION K. Tsuda, S. Tsuda, I. Nishio, Y. Masuyama. 1Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama,, Japan It has been shown that hormone replacement therapy with estrogen and progesterone provides protection against the development of hypertension, arteriosclerosis and other cardiovascular diseases. However, the precise mechanism underlying its benefits is unclear. Our recent study demostrated that estrogen improved membrane microviscosity of erythrocytes. In the present study, we examined the effects of progesterone on membrane fluidity of erythrocytes in normotensive subjects by means of an electron paramagnetic resonance (EPR) and spinlabeling method. Progesterone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes (S: control 0.726⫾0.002, mean⫾SEM, n⫽31, prog 10-9mol/L 0.715⫾0.002, n⫽31, p⬍0.05, prog 10-8mol/L 0.710⫾0.002, n⫽31, P⬍0.05). The finding showed that progesterone increased the membrane fluidity of erythrocytes. The effect of 0895-7061/01/$20.00
progesterone was potentiated by the nitric oxide (NO)-donor, S-nitrosoN-acetylpenicillamine (SNAP) and a cGMP analog, 8-bromo-cGMP. In contrast, the progesterone-induced changes in membrane fluidity were significantly reversed in the presence of the NO synthase inhibitors, L-NG-nitroarginine-methyl-ester (L-NAME) and asymmetric dimethylL-arginine (ADMA). These results showed that progesterone increased membrane fluidity of erythrocytes and improved microviscosity of cell membranes by the NO-dependent mechanism. Furthermore, the data strongly suggest that progesterone might actively participate in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation. Key Words: Progesterone, Nitric oxide, Membrane fluidity
P-689 AMBULATORY BLOOD PRESSURE MONITORING, UTERINE RESISTANCES AND CARDIOVASCULAR TESTS AS PREDICTORS OF PREGNANCY-INDUCED HYPERTENSION Giovanna Franconi, Herbert Valensise, Ambrogio Capria, Angela Ciamei, Doriana Frongillo, Fabiola Antonucci, Carlo Romanini. 1 Clinica Medica, Tor Vergata University, Rome, Italy, 2Clinica Ostetrica e Ginecologica, Tor Vergata University, Rome, Italy Several blood pressure (BP) and autonomic abnormalities have been associated with pregnancy-induced hypertension (PIH) but no noninvasive method has been identified as able to predict the development of PIH. In the present study we examined prospectively 45 consecutive normotensive pregnant women aged 29.9 ⫹ 3.3 years at 27 ⫹ 4 gestational week, referred to an institutional tertiary care referral center for known risk factors for developing PIH: pre-eclampsia and/or intrauterine growth retardation in previous pregnancy, or abnormal laboratory tests in present pregnancy (hypocalcemia, hyperuricemia). The following tests were performed: echo-Doppler of uterine arteries to evaluate uteroplacental resistance index (URI), ambulatory blood pressure monitoring (ABPM) to measure the systolic and diastolic MESOR (Midline Estimating Statistic of Rhythm) defined as the average value of the rhythmic function fitted to the blood pressure data, cardiovascular tests to evaluate the autonomic nervous function (Valsalva manoeuvre, deep breathing test, lying-to-standing test, cold pressor test, isometric handgrip, and power spectral analysis of heart rate variability). Unpaired t test was used to evaluate differences between normotensive and hypertensive women. The logistic regression model with backward selection was used to estimate the probability of PIH. Eighteen women (40 %) developed gestational hypertension. Compared to normotensives, women who developed PIH showed higher systolic (120 ⫾ 6 vs. 114 ⫾ 8 mm Hg respectively; p⬍0.05) and diastolic MESOR (75 ⫾ 4 vs. 68 ⫾ 5 mm Hg respectively; p⬍ 0.001). The systolic response to Valsalva manoeuvre was significantly increased in women who developed PIH with respect to normotensives (35 ⫾ 10 vs. 29 ⫾ 9 mm Hg, respectively; p⬍0.05) indicating a sympathetic activation in women with PIH. Power spectral analysis of heart rate variability did not show any significant difference between normotensive women and women who developed PIH. No difference in URI was found between subjects developing hypertension and normotensive women. Logistic regression analysis showed that all variables correctly predicted 88.9% normotensive women and 83.3% women who developed hypertension. Overall prediction was 86.7%. The most relevant parameter for predicting the development of PIH was diastolic MESOR. Cardiovascular tests improved the prediction of PIH. The study shows that ABPM could have a role in the screening of pregnant women at risk of developing hypertension. Key Words: Pregnancy, Heart rate variability, Ambulatory blood pressure monitoring © 2001 by the American Journal of Hypertension, Ltd. Published by Elsevier Science Inc.
POSTERS: Women’s Health
AJH–April 2001–VOL. 14, NO. 4, PART 2
P-687 EFFECT OF ESTROGEN REPLACEMENT THERAPY ON BLOOD PRESSURE, RENIN-ANGIOTENSIN SYSTEM, AND INTRACELLULAR ELECTROLYTES Marı´a Queralt Cardona, Marı´a Mongay, Alejandro de la Sierra. 1 Hypertension Unit, Hospital Clinic, Barcelona, Spain The aim of the study was to evaluate the effect of estrogen replacement therapy (ERT) on blood pressure (BP) assessed by both office and by 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we studied variations in biochemical and hormonal parameters that may represent possible mechanisms responsible for the BP effect. Thirty-five postmenopausal (mean age : 55 ⫾ 4 years) stage I hypertensive women not receiving antihypertensive treatment were studied. Patients were randomized to ERT (estradiol 50 mg plus medroxyprogesterone 5 mg) or no treatment (control group) for a 12-week period. At both baseline and at the end of treatment period we measured BP in the office and by 24-hour ABPM, biochemical parameters, plasma renin activity (PRA), plasma aldosterone and norepinephrine, as well as intraerythrocyte sodium concentration [Nai] and intraplatelet free calcium concentration [Cai]. The main results showed that ERT significantly (*p⬍0.05) decreased 24-hour, but not office systolic and diastolic BP. ERT also decreased plasma aldosterone levels and intraerythrocyte sodium concentration. In conclusion, treatment with ERT in hypertensive postmenopausal women significantly decreases BP, assessed by 24-hour ABPM. A decrease in RAS activity and in intracellular sodium concentration may represent possible responsible mechanisms Parameter
ERT (Nⴝ18) Baseline 12-week
Control (Nⴝ17) Baseline 12-week
Office SBP 165.9 ⫾ 14.3 162.5 ⫾ 15.9 164.9 ⫾ 13.3 165.8 ⫾ 19.4 Office DBP 97.1 ⫾ 6.8 95.1 ⫾ 7.4 96.4 ⫾ 5.4 95.6 ⫾ 7.4 24-h SBP 139.1 ⫾ 11.6 133.3 ⫾ 11.3* 141.6 ⫾ 16.7 144.6 ⫾ 17.9 24h DBP 86.2 ⫾ 8.2 82.2 ⫾ 8.6* 85.8 ⫾ 6.3 87.1 ⫾ 6.1 PRA (ng/mL/h) 0.21 ⫾ 0.15 0.17 ⫾ 0.14 0.11 ⫾ 0.07 0.15 ⫾ 0.18 Aldosterone (ng/dL) 14.8 ⫾ 9.1 10.6 ⫾ 6.4* 11.7 ⫾ 5.5 15.1 ⫾ 7.9 Norepinephrine 270 ⫾ 112 397 ⫾ 205 306 ⫾ 195 335 ⫾ 125 (pg/mL) [Nai] (mmol/L) 9.4 ⫾ 1.6 8.3 ⫾ 1.2* 8.7 ⫾ 1.1 9.0 ⫾ 1.4 [Cai] (nmol/L) 29.3 ⫾ 4.8 30.5 ⫾ 4.5 30.5 ⫾ 9.4 31.3 ⫾ 4.2
Key Words: Intracellular Electrolytes, Estrogen Replacement Therapy, Ambulatory Blood Pressure Monitoring
P-688 PROGESTERONE IMPROVES MEMBRANE FUNCTION OF ERYTHROCYTES BY THE NITRIC OXIDE-DEPENDENT MECHANISM -AN ELECTRON PARAMAGNETIC RESONANCE INVESTIGATION K. Tsuda, S. Tsuda, I. Nishio, Y. Masuyama. 1Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama,, Japan It has been shown that hormone replacement therapy with estrogen and progesterone provides protection against the development of hypertension, arteriosclerosis and other cardiovascular diseases. However, the precise mechanism underlying its benefits is unclear. Our recent study demostrated that estrogen improved membrane microviscosity of erythrocytes. In the present study, we examined the effects of progesterone on membrane fluidity of erythrocytes in normotensive subjects by means of an electron paramagnetic resonance (EPR) and spinlabeling method. Progesterone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes (S: control 0.726⫾0.002, mean⫾SEM, n⫽31, prog 10-9mol/L 0.715⫾0.002, n⫽31, p⬍0.05, prog 10-8mol/L 0.710⫾0.002, n⫽31, P⬍0.05). The finding showed that progesterone increased the membrane fluidity of erythrocytes. The effect of 0895-7061/01/$20.00
progesterone was potentiated by the nitric oxide (NO)-donor, S-nitrosoN-acetylpenicillamine (SNAP) and a cGMP analog, 8-bromo-cGMP. In contrast, the progesterone-induced changes in membrane fluidity were significantly reversed in the presence of the NO synthase inhibitors, L-NG-nitroarginine-methyl-ester (L-NAME) and asymmetric dimethylL-arginine (ADMA). These results showed that progesterone increased membrane fluidity of erythrocytes and improved microviscosity of cell membranes by the NO-dependent mechanism. Furthermore, the data strongly suggest that progesterone might actively participate in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation. Key Words: Progesterone, Nitric oxide, Membrane fluidity
P-689 AMBULATORY BLOOD PRESSURE MONITORING, UTERINE RESISTANCES AND CARDIOVASCULAR TESTS AS PREDICTORS OF PREGNANCY-INDUCED HYPERTENSION Giovanna Franconi, Herbert Valensise, Ambrogio Capria, Angela Ciamei, Doriana Frongillo, Fabiola Antonucci, Carlo Romanini. 1 Clinica Medica, Tor Vergata University, Rome, Italy, 2Clinica Ostetrica e Ginecologica, Tor Vergata University, Rome, Italy Several blood pressure (BP) and autonomic abnormalities have been associated with pregnancy-induced hypertension (PIH) but no noninvasive method has been identified as able to predict the development of PIH. In the present study we examined prospectively 45 consecutive normotensive pregnant women aged 29.9 ⫹ 3.3 years at 27 ⫹ 4 gestational week, referred to an institutional tertiary care referral center for known risk factors for developing PIH: pre-eclampsia and/or intrauterine growth retardation in previous pregnancy, or abnormal laboratory tests in present pregnancy (hypocalcemia, hyperuricemia). The following tests were performed: echo-Doppler of uterine arteries to evaluate uteroplacental resistance index (URI), ambulatory blood pressure monitoring (ABPM) to measure the systolic and diastolic MESOR (Midline Estimating Statistic of Rhythm) defined as the average value of the rhythmic function fitted to the blood pressure data, cardiovascular tests to evaluate the autonomic nervous function (Valsalva manoeuvre, deep breathing test, lying-to-standing test, cold pressor test, isometric handgrip, and power spectral analysis of heart rate variability). Unpaired t test was used to evaluate differences between normotensive and hypertensive women. The logistic regression model with backward selection was used to estimate the probability of PIH. Eighteen women (40 %) developed gestational hypertension. Compared to normotensives, women who developed PIH showed higher systolic (120 ⫾ 6 vs. 114 ⫾ 8 mm Hg respectively; p⬍0.05) and diastolic MESOR (75 ⫾ 4 vs. 68 ⫾ 5 mm Hg respectively; p⬍ 0.001). The systolic response to Valsalva manoeuvre was significantly increased in women who developed PIH with respect to normotensives (35 ⫾ 10 vs. 29 ⫾ 9 mm Hg, respectively; p⬍0.05) indicating a sympathetic activation in women with PIH. Power spectral analysis of heart rate variability did not show any significant difference between normotensive women and women who developed PIH. No difference in URI was found between subjects developing hypertension and normotensive women. Logistic regression analysis showed that all variables correctly predicted 88.9% normotensive women and 83.3% women who developed hypertension. Overall prediction was 86.7%. The most relevant parameter for predicting the development of PIH was diastolic MESOR. Cardiovascular tests improved the prediction of PIH. The study shows that ABPM could have a role in the screening of pregnant women at risk of developing hypertension. Key Words: Pregnancy, Heart rate variability, Ambulatory blood pressure monitoring © 2001 by the American Journal of Hypertension, Ltd. Published by Elsevier Science Inc.