Endothelial dysfunction and alteration of nitric oxide cyclic GMP pathway in patients with exercise-induced hypertension

The diagnostic and prognostic implication of exaggerated blood pressure response to exercise have been controversial, with opinions ranging from a benign process to a harbinger of potential cardiovascular morbidity. Endothelial dysfunction has been demonstrated in patients with atherosclerosis and as a risk factor for coronary artery disease. However, whether the cause of exercise-induced hypertension might be related to endothelial dysfunction has not been well elucidated. We evaluated endothelial function in. patients who showed a systolic blood pressure greater than or equal to210 mmHg in males and greater than or equal to190 mmHg in females during treadmill exercise test. We measured the endothelial function of the brachial artery in 35 patients with exercise-induced hypertension, and in 35 age- and gender-matched normal control subjects, by a high resolution ultrasound technique, and the concentration of NO2-/NO3- and cyclic guanosine monophosphate (GMP). Endothelial-dependent vasodilation was impaired in patients with hypertension compared to normal controls (3.14 +/- 0.61 vs. 6.5 +/- 0.76%, p <0.05). The extent of vasodilation was significantly correlated with age (r=-0.28, p<0.05) and systolic blood pressure difference (r=-0.36, p<0.05). The levels of NO2-/NO3- and cyclic GMP at maximal exercise were significantly higher than those at rest and recovery in both controls and the hypertensive group (p < 0.05). Although there was no significant difference in the increment of NO2-/NO3- during maximal exercise between the controls and hypertensive group (55 17 vs. 56 +/- 12 mumol/L, p=NS), cyclic GMP level during maximal exercise was significantly higher in the control group than the hypertensive group (10 +/- 1.8 vs. 8.3 +/- 2.5 pmol/ml, p < 0.05). Patients with exercise-induced hypertension have poor endothelium-dependent vasodilation due to an impaired nitric oxide/cyclic GMP pathway, which may play a significant role in increasing blood pressure during exercise with inadequate peripheral adjustment to changing cardiac output.