ABSTRACT
The above-mentioned dysregulation is not limited only to the parasympathetic function, but affects sympathetic cardiovascular control as well. Multifold evidence supports this statement. In a meta-analysis of all published studies, Goldstein reported that, even accounting for some negative results, an indirect marker of sympathetic tone, such as plasma norepinephrine, is significantly elevated in essential hypertensive patients as compared to age-matched normotensive subjects (13). Furthermore, by employing the technique based on the intravenous tracer infusion of small doses of radiolabeled norepinephrine, Esler and coworkers were able to show that the rate of norepinephrine spillover from the neuroeffector junctions is increased in young subjects with a most borderline blood pressure (BP) elevation, and that this enhanced release takes place particularly in the kidney and in the heart, i.e., two organs of key importance in BP homeostatic control (14). Further evidence comes from the direct measurement of sympathetic nerve traffic to the skeletal muscle circulation, a technique which has allowed for documentation of an increase in central sympathetic outflow in young, borderline hypertensives (15). Finally, evidence indicates that, while parasympathetic dysfunction remains stable in the hypertensive state, characterized by more severe increases in BP, sympathetic activation
undergoes a progressive and further potentiation. This has been shown by a study performed by our group (16), in which we quantified sympathetic nerve traffic to the skeletal muscle district in three groups of age-matched subjects: with normal BP, with moderate essential hypertension, and with essential hypertension of a more severe degree. As shown in Figure 13.1, the progressive increase in BP values observed in these three conditions was paralleled by a progressive and marked elevation in sympathetic nerve traffic, suggesting the key role of adrenergic neural factors, not only in the development, but also in the progression, of the hypertensive state. A further demonstration of this phenomenon comes from evidence, collected years ago by our group, that BP variability, i.e., the magnitude of the BP oscillations occurring during the daytime and nighttime, which is largely dependent on adrenergic influences, causes an increase in hypertension, and progresses when hypertension becomes more severe (17).
