Pressor hyperreactivity to mental and hand-grip stresses in patients with hypercholesterolemia

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.