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Hypertension in normal-weight and obese individuals is characterized by activation of the sympathetic nervous system. Measurement of spillover of the sympathetic transmitter, norepinephrine, to plasma indicates that the regional pattern of sympathetic activation in the 2 "variants" of essential hypertension differs, excluding the heart in obesity-related hypertension. Whether sympathetic nerve firing characteristics also differ is unknown. We studied multiunit and single fiber sympathetic nerve firing properties in patients with normal-weight hypertension and obesity-related hypertension, comparing these with nerve characteristics in normal-weight and obese people with normal blood pressure. Both normal-weight hypertensive (n=10) and obese hypertensive (n=14) patients had increased total multiunit muscle sympathetic nerve activity compared with the normal-weight (n=11) and obese (n=11) people with normal blood pressure (65+/-4 versus 47+/-6 bursts per 100 heartbeats, P<0.01 in the normal-weight groups and 68+/-4 versus 53+/-3 bursts per 100 beats, P<0.01 in the obese groups). Sympathetic activation in normal-weight hypertension was characterized by increased firing rate of single vasoconstrictor fibers (70+/-8 versus 28+/-3 spikes per 100 beats; P<0.001), increased firing probability per heartbeat (39+/-3% versus 20+/-3%; P<0.001), and higher incidence of multiple spikes per heartbeat (30+/-4% versus 17+/-4%; P<0.05). Sympathetic activation in obesity-related hypertension differed, involving recruitment of previously silent fibers, which fired at a normal rate. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of both the firing characteristics of individual sympathetic fibers and the sympathetic outflows involved. The underlying central nervous system mechanism and the adverse consequences of the 2 modes of sympathetic activation may differ.

Patients with panic disorder are at increased cardiac risk. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system may be implicated. Using isotope dilution methodology, investigations of whole-body and regional sympathetic nervous activity have failed to show any differences between patients with panic disorder and healthy subjects. Using direct recording of single unit efferent sympathetic vasoconstrictor nerve activity by microneurography we examined sympathetic nervous function in patients with panic disorder more precisely than previously reported. The activity of multiunit and single unit vasoconstrictor sympathetic nerves was recorded at rest at the level of the peroneal nerve in 10 patients diagnosed with panic disorder and in nine matched healthy volunteers. Multiunit sympathetic activity was not different between the two groups (26+/-3 bursts min-1 in patients with panic disorder and 28+/-3 bursts min-1 in controls). The firing frequency of single unit vasoconstrictor neurones was also similar between the two groups (0.38+/-0.09 versus 0.22+/-0.03 Hz). However, the probability of firing during a sympathetic burst was higher in patients with panic disorder compared with healthy controls (45+/-5%versus 32+/-3%, P<0.05). When only the neural bursts during which the vasoconstrictor neurone was active were considered, we found that in patients with panic disorder the neurones tended to fire more often in a 'multiple spike' pattern than in the controls (i.e. the probability of the neurone firing twice was 25+/-3% in patients with panic disorder compared with 14+/-3% in controls). Quantification from single vasoconstrictor unit recording provides evidence of a disturbed sympathetic firing pattern in patients with panic disorder.

Cardiac-specific overexpression of nerve growth factor (NGF), a neurotrophin, leads to sympathetic hyperinnervation of heart. As a consequence, adverse functional changes that occur after chronically enhanced sympathoadrenergic stimulation of heart might develop in this model. However, NGF also facilitates synaptic transmission and norepinephrine uptake, effects that would be expected to restrain such deleterious outcomes. To test this, we examined 5- to 6-mo-old transgenic (TG) mice that overexpress NGF in heart and their wild-type (WT) littermates using echocardiography, invasive catheterization, histology, and catecholamine assays. In TG mice, hypertrophy of the right ventricle was evident (+67%), but the left ventricle was only mildly affected (+17%). Left ventricular (LV) fractional shortening and fractional area change values as indicated by echocardiography were similar between the two groups. Catheterization experiments revealed that LV +/-dP/dt values were comparable between TG and WT mice and responded similarly upon isoproterenol stimulation, which indicates lack of beta-adrenergic receptor dysfunction. Although norepinephrine levels in TG LV tissue were approximately twofold those of WT tissue, TG plasma levels of the neuronal norepinephrine metabolite dihydroxyphenylglycol were fivefold those of WT plasma. A greater neuronal uptake activity was also observed in TG LV tissue. In conclusion, overexpression of NGF in heart leads to sympathetic hyperinnervation that is not associated with detrimental effects on LV performance and is likely due to concomitantly enhanced norepinephrine neuronal uptake.