The mechanisms affecting recruitment patterns of postganglionic sympathetic nerves remain unclear. The divergent and convergent preganglionic innervation patterns of postganglionic neurons, and presence of differently-sized postganglionic nerves, suggest that the ganglia may participate in modifying the discharge patterns of single sympathetic postganglionic neurons innervating the skeletal muscle circulation. Whether the ganglia affect the ordered behaviour of varying sized postganglionic sympathetic neurons in humans has not been studied. Trimethaphan infusion produced an ordered pattern of action potential (AP) de-recruitment whereby the firing of larger, low probability APs present at baseline was abolished first, followed by progressive decreased probability of smaller APs. Although integrated sympathetic bursts were no longer detected after several minutes of trimethaphan, firing of the smallest APs was detected. These data suggest the ganglia affect the distribution of firing probabilities exhibited by differently-sized sympathetic neurons. The ganglia may contribute to sympathetic neural emission patterns involved in homeostatic regulation.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure (P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women (P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women (P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women (P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group (P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

The autonomic nervous system plays a central role in both acute and chronic blood pressure regulation in humans. The activity of the sympathetic branch of the autonomic nervous system is positively associated with peripheral resistance, an important determinant of mean arterial pressure in men. In contrast, there is no association between sympathetic nerve activity and peripheral resistance in women before menopause, yet a positive association after menopause. We hypothesized that autonomic support of blood pressure is higher after menopause in women. We examined the effect of ganglionic blockade on arterial blood pressure and how this relates to baseline muscle sympathetic nerve activity in 12 young (25±1 years) and 12 older postmenopausal (61±2 years) women. The women were studied before and during autonomic blockade using trimethaphan camsylate. At baseline, muscle sympathetic nerve activity burst frequency and burst incidence were higher in the older women (33±3 versus 15±1 bursts/min; 57±5 versus 25±2 bursts/100 heartbeats, respectively; P<0.05). Muscle sympathetic nerve activity bursts were abolished by trimethaphan within minutes. Older women had a greater decrease in mean arterial pressure (-29±2 versus -9±2 mm Hg; P<0.01) and total peripheral resistance (-10±1 versus -5±1 mm Hg/L per minute; P<0.01) during trimethaphan. Baseline muscle sympathetic nerve activity was associated with the decrease in mean arterial pressure during trimethaphan (r=-0.74; P<0.05). In summary, our results suggest that autonomic support of blood pressure is greater in older women compared with young women and that elevated sympathetic nerve activity in older women contributes importantly to the increased incidence of hypertension after menopause.

Functional magnetic resonance imaging (fMRI) provides an indirect measure of cerebral activation that could be altered by factors directly affecting cerebral blood flow independent of changes in neuronal activation. Presently, we investigate how changes in blood pressure (BP) affect the activation detected with fMRI. fMRI scans were acquired in 33 rats under control conditions and following transient BP increases (norepinephrine, IV) or decreases (arfonad, IV) with and without electrical stimulation of the forepaw. Voxels correlating to either the stimulation or the change in BP time courses were identified. During transient hypertension, irrespective of forepaw stimulation, BP increases (i.e., >10 mm Hg) produced a transient increase in the blood oxygen level-dependent (BOLD) intensity resulting in a significant numbers of voxels correlating to the BP time courses (P < 0.05), and the number of these voxels increased as BP increased, becoming substantial at BP > 30 mm Hg. The activation patterns with BP increases and stimulation overlapped spatially resulting in an enhanced cerebral activation to simultaneous forepaw stimulation (P < 0.05). BP decreases (>10 mm Hg) produced corresponding decreases in BOLD intensity, causing significant numbers of voxels correlating to the BP decreases (P < 0.005), and these numbers increased as BP decreased (P < 0.001). The BP decreases and stimulation time courses and responses were distinct, and hypotension did not affect the detection of the activation response to forepaw stimulation. The results indicate that substantial hypertension accompanying a stimulation paradigm produces a BOLD response that enhances the cerebral activation detected, whereas hypotension does not affect the detection of neuronal activation but does produce responses that could be interpreted as a 'deactivation'.

In acute experiments on cats neural inotropic and lusitropic reactions of the heart to enhancement of pre- and afterload were assessed by changes in contractility and relaxation indices, which were preliminary chosen for their maximum specificity and sensitivity. The control cardiac responses to increased pre- and afterload were measured after treatment with ganglionic blocker arfonad. The myogenic component of these responses assessed under the action of arfonad was highly pronounced, therefore the neural inotropic and lusitropic reactions were measured as the difference between load-induced changes of indices in experiments with and without arfonad. Increased preload produced similar negative inotropic and lusitropic effects, while increased afterload produced a more pronounced negative inotropic effect, which indicated independent regulation of contractility and diastolic relaxation of the heart.

The possibility of using contraction and relaxation indices for evaluation of inotropic and loositropic influences on the heart was studied in experiments on cats. Increased pre- and afterload were used as the stimuli, which are simultaneously loading and reflexogenic. Under conditions of preserved innervation both stimuli elevated the indices selected according to the highest sensitivity/specificity ratio. Ganglionic blocker arfonad potentiated the effects of these stimuli. This attests to a considerable contribution of the myogenic component to the changes in the studied indices in response to increased pre- and afterload and to the existence of negative inotropic and loositropic influences on the heart under conditions of preserved innervation. These conclusions were supported when more specific indices were used: in most cases they decreased during load tests. Thus, when the contraction and relaxation indices are used for evaluation inotropic and loositropic influences on the heart, it seems reasonable either to compare heart responses under conditions of preserved or blocked innervation, or to apply more specific indices. Analysis of changes in most widely used indices (dP/dt)max and t showed that t reliably reflects neural loositropic influences, while the use of (dP/dt)max without proper control can be erroneous.

Sensitivity (response to epinephrine infusion) and specificity (response to changes in pre- and afterload) of some cardiac relaxation indices were compared in acute experiments on cats treated with ganglionic blocker arfonad. Some new indices proposed by us provide better characteristics than widely used relaxation time constant (t) and maximum first derivative of the left ventricular pressure (-dP/dt)max.

The high-frequency (HF) component of the heart rate variability (HRV) is regarded as an index of cardiac vagal responsiveness. However, when vagal tone is decreased, nonneural mechanisms could account for a significant proportion of the HF component. To test this hypothesis, we examined the HRV spectral power in 20 patients with mild chronic heart failure (CHF) and 11 controls before and during ganglion blockade with trimethaphan camsylate (3-6 mg/min iv). A small HF component was still present during ganglion blockade, and its amplitude did not differ between CHF patients and controls. The average contribution of nonneural oscillations to the HF component was 15% (range 1-77%) in patients with CHF and 3% (range 0. 7-30%) in healthy controls (P < 0.005). During controlled breathing at 0.16 Hz, however, it decreased to 1% (range 0.2-13%) in healthy controls and 5% (range 1-44%) in CHF patients. Our results indicate that the HF component can significantly overestimate cardiac vagal responsiveness in patients with mild CHF. This bias is improved by controlled breathing, since this maneuver increases the vagal contribution to HF without affecting its nonneural component.

Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP.