Minami M, Atarashi K, Ishiyama A, Hirata Y, Goto A, Omata M
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Hypertens. 1999 Feb;17(2):185-92. doi: 10.1097/00004872-199917020-00002.
To investigate the role of hypercholesterolemia in the regulation of blood pressure.
We compared blood pressure responses to arithmetic stress and hand-grip tests in normotensive patients with hypercholesterolemia n = 15) and a mean (+/- SEM) age of 49 +/- 3 years, and normal cholesterolemic controls (n = 22) aged 48 +/- 1 years. Blood pressure and heart rate were measured throughout the tests. We examined the intracellular Ca2+ concentration in platelets with or without low-density-lipoprotein stimulation (2.9 nmol/l, 10 mg/ml). The plasma nitrite plus nitrate and cyclic GMP were determined before and at the end of each test to evaluate nitric oxide production and activity.
Both tests showed that systolic/diastolic blood pressure was higher in the hypercholesterolemic patients than in the normal controls (stress test: 139 +/- 3/91 +/- 4 versus 127 +/- 2/80 +/- 3 mmHg, P < 0.01/P < 0.05; hand-grip test: 164 +/- 5/106 +/- 5 versus 144 +/- 3/88 +/- 3 mmHg, P < 0.01/P < 0.01). The intracellular Ca2+ concentration in platelets and the increase in response to low-density-lipoprotein stimulation were higher in the hypercholesterolemic patients (without stimulation: 72 +/- 3 versus 64 +/- 3 nmol/l, P < 0.01; with 2.9 nmol/l stimulation: 145 +/- 21 versus 89 +/- 6 nmol/l, P < 0.01). The increase in Ca2+ in response to 2.9 nmol/ml stimulation with low-density lipoprotein was positively related to the increase in mean blood pressure in response to the stress test (r = 0.56, P < 0.002). Nitric oxide production appeared to be increased in the hypercholesterolemic patients (65 +/- 5 versus 51 +/- 4 mmol/l, P < 0.05), and was not affected significantly by the tests. In contrast, cyclic GMP was lower in the patients and was increased significantly in the normal controls by the hand-grip test (P < 0.05). As a result, plasma cyclic GMP was lower in the patients (1.9 +/- 0.2 versus 2.5 +/- 0.1 nmol/l, P < 0.01). The ratio of plasma cyclic GMP to nitric oxide was also lower in the hypercholesterolemic patients at rest (P < 0.05), and at the end of the mental stress (P < 0.02) and hand-grip (P < 0.001) tests.
Patients with hypercholesterolemia showed an exaggerated blood pressure response to both mental stress and exercise, even if resting blood pressure was normal. Increases in the intracellular Ca2+ concentration can contribute to these excessive responses. A disproportionately lower level of cyclic GMP to nitric oxide in plasma may also be involved in these abnormal responses.
研究高胆固醇血症在血压调节中的作用。
我们比较了高胆固醇血症的血压正常患者（n = 15，平均年龄49±3岁）和胆固醇正常的对照者（n = 22，年龄48±1岁）对算术应激和握力测试的血压反应。在整个测试过程中测量血压和心率。我们检测了有无低密度脂蛋白刺激（2.9 nmol/l，10 mg/ml）时血小板内的Ca2+浓度。在每次测试前和结束时测定血浆亚硝酸盐加硝酸盐以及环磷酸鸟苷，以评估一氧化氮的产生和活性。
两项测试均显示，高胆固醇血症患者的收缩压/舒张压高于正常对照组（应激测试：139±3/91±4 mmHg对127±2/80±3 mmHg，P < 0.01/P < 0.05；握力测试：164±5/106±5 mmHg对144±3/88±3 mmHg，P < 0.01/P < 0.01）。高胆固醇血症患者血小板内的Ca2+浓度以及对低密度脂蛋白刺激的反应性升高（无刺激时：72±3对64±3 nmol/l，P < 0.01；2.9 nmol/l刺激时：145±21对89±6 nmol/l，P < 0.01）。对2.9 nmol/ml低密度脂蛋白刺激的Ca2+反应性升高与应激测试时平均血压的升高呈正相关（r = 0.56，P < 0.002）。高胆固醇血症患者的一氧化氮产生似乎增加（65±5对51±4 mmol/l，P < 0.05），且不受测试的显著影响。相比之下，患者的环磷酸鸟苷水平较低，握力测试使正常对照组的环磷酸鸟苷水平显著升高（P < 0.05）。结果，患者的血浆环磷酸鸟苷水平较低（1.9±0.2对2.5±0.1 nmol/l，P < 0.01）。高胆固醇血症患者在静息时（P < 0.05）、精神应激结束时（P < 0.02）和握力测试结束时（P < 0.001）血浆环磷酸鸟苷与一氧化氮的比值也较低。
高胆固醇血症患者即使静息血压正常，对精神应激和运动的血压反应也会过度。细胞内Ca2+浓度升高可能导致这些过度反应。血浆中环磷酸鸟苷与一氧化氮水平不成比例地降低也可能参与这些异常反应。
