Insulin resistance in essential hypertension: a psychophysiological approach to the "chicken and egg" question.

AIMS: High levels of plasma insulin have frequently been found in patients with high blood pressure. The causal role of insulin resistance in essential hypertension, however, is still debated. Epidemiological and clinical studies have not provided complete responses to the original pathophysiological speculations, while the suggestion that enhanced sympathetic tone may induce both insulin resistance and hypertension is gaining ground. DATA SYNTHESIS: Many studies indicate that the high sympathetic drive in hypertensive patients originates within the brain, while other studies show that insulin resistance is associated with reduced vasodilatory capacity and increased vasoconstrictive functional responses ascribed to endothelial impairment. The sympathetic overdrive and enhanced cardiovascular reactivity, detectable since the earliest stages of hypertension lead to endothelial damage and, hence, impair the vasodilatory response, peripheral blood flow and flow-dependent metabolism. Thus, the link between hyperinsulinemia and high blood pressure might lie in the vascular abnormalities secondary to elevated sympathetic tone and exaggerated hemodynamic stress response. CONCLUSIONS: Examination of the literature and the results of recent pilot studies of the stress systemic and regional hemodynamic reactivity in the present paper suggests that behavioral characteristics and cardiovascular stress responses play a pivotal role in determining the hyperinsulinemic state in hypertensive patients. High sympathetic tone, with consequent vascular impairment and altered functional responses, may be the primary event causing hyperinsulinemia and start very early in patients with high blood pressure. In turn, hyperinsulinemia further contributes to vascular damage and aggravates the metabolic and hypertensive disease.

Microvascular changes during laboratory stimuli and structural haemodynamic indices: the role of pulse pressure.

Office and ambulatory pulse pressure have been recognized as independent predictors of cardiovascular mortality and atherosclerosis in hypertensives as well as in normotensives. On the other hand, the vascular reactivity, in subjects with high pulsatile component of blood pressure, has not been studied yet. The purpose of our study was to identify the regional muscular hemodynamics and the cutaneous microvascular changes during laboratory stimuli in young adult very mild hypertensives with high pulse pressure. The cardiovascular (Finapres), the forearm vascular (plethysmography) and the microvascular cutaneous (laser-Doppler flowmetry and transcutaneous oximetry) responses to psychophysiological stimuli were measured. In addition, the hyperemic forearm vascular response to the ischaemic test was measured as haemodynamic index of vascular damage. We studied 15 very mild hypertensives with higher office pulse pressure and 15 patients with similar age, history of hypertension, metabolic parameters and systodiastolic blood pressure but lower pulse pressure values. Patients with high pulse pressure demonstrated reduced hyperemic response and increased residual vascular resistance at the forearm ischaemic test. They did not vary for all the parameters, except pulse pressure, during the baseline period but the total stress response, as residualized area-under-the-curve, was notably different. Patients with higher office pulse pressure demonstrated a significant increased heart rate, systolic and pulsatile blood pressure reactivity. On the contrary, they showed a reduced forearm and cutaneous blood flow response combined to a reduced transcutaneous tissutal oxygenation. The findings suggest that the increased pulsatile component of blood pressure might be associated to structural and functional vascular impairments since the very early stages of hypertension in young adults without metabolic disorders.

Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses.

Many biological and psychological factors induce haemodynamic and extra-cardiovascular functional changes mediated by the autonomic nervous system. Pharmacological blood pressure reduction, as a neurovegetative stimulus, can change the arousal of the sympathetic nervous system. We evaluated the effects of two calcium channel blockers, verapamil and amlodipine, both administered as monotherapies, upon the sympathetic stress response in 23 randomized mild-to-moderate essential hypertensives (161 +/- 2/98 +/- 1 mmHg). Patients performed four stress tests (mental arithmetic, colour word Stroop, cold pressor and handgrip) while extracardiovascular and haemodynamic functions were assessed non-invasively at every heart beat, during baseline, stress and recovery phases. The sympathetic response was evaluated by computing the 'area-under-the-curve' (value x time) measured during the psychophysiological session. The session was repeated at run-in, after placebo and during treatment. After one month's treatment, baseline blood pressure was significantly reduced in patients treated with amlodipine (139 +/- 1/84 +/- 1 mmHg; P < 0.001) and verapamil (140 +/- 2/85 +/- 1 mmHg; P < 0.001). The emotional arousal (frontalis muscular contraction, skin conductance) was unchanged, but the cutaneous vascular response was reduced (P < 0.05) in patients treated with verapamil. No changes in systolic or diastolic blood pressure were detectable, but amlodipine increased the heart rate response (P < 0.05). In contrast, verapamil reduced the heart rate (P < 0.05) without depressing the cardiac output response, which was increased with amlodipine (P < 0.05). Total vascular resistance was significantly (P < 0.001) reduced with both the treatments. Consequently, functional cardiac load, expressed by pressure-rate product and cardiac power, was significantly enhanced with amlodipine and reduced with verapamil. In conclusion, the abnormal sympathetic stress response, which characterizes the hypertensive patient, might be affected by the choice of medication. Verapamil in particular, moderated emotional arousal, the vasoconstrictive response and reduced cardiac load without lowering cardiac output demands. In contrast, in patients treated with amlodipine, in whom the cardiac output response was increased, the pattern was reversed and the functional cardiac load was also increased.

Stress reactivity in responder and non-responder hypertensives treated with verapamil and enalapril.

Hypertension was found to be associated with sympathetic overdrive but it is still debated if the antihypertensive agents can differently affect the stress response in hypertensive subjects. Through a psychophysiological study, we evaluated the effect of verapamil (V) and enalapril (E), both as monotherapy and association. Office BP was successfully reduced (< 145/90 mmHg) in 11 patients treated with V (V-Resp) and in 10 patients treated with E (E-Resp). Both the drugs were prescribed in 9 patients (V+E) who did not sufficiently lower their blood pressure (N-Resp) with monotherapy. Patients performed three stressors (color word stroop, cold pressor and handgrip). Extracardiovascular and hemodynamic functions were measured during baseline, stress and recovery periods. The response was evaluated adding the changes occurred in every phase of the psychophysiological session. This was performed before run-in and after any modification of the therapeutic intervention. The emotional arousal (phrontalis muscular contraction, skin conductance, peripheral temperature) was reduced when BP was normal. No change in BP reactivity was found. HR response decreased in V-Resp and cardiac output increased in E-Resp while the vascular reaction was restrained in E-Resp and V-Resp. This was reduced also in N-Resp when they assumed V+E and normalized their arterial pressure. The findings indicate that the sympathetic reactivity may be modified by the therapy. In particular, verapamil restrained the cardiac stress response without lowering the cardiac output and was advantageously associated with enalapril to control the psychophysiological response in more resistant hypertensive patients.