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

OBJECTIVE

To investigate the role of hypercholesterolemia in the regulation of blood pressure.

SUBJECTS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.