A sympathetic view of the sympathetic nervous system and human blood pressure regulation

Abstract

New ideas about the relative importance of the autonomic nervous system (and especially its sympathetic arm) in long-term blood pressure regulation are emerging. It is well known that mean arterial blood pressure is normally regulated in a fairly narrow range at rest and that blood pressure is also able to rise and fall 'appropriately' to meet the demands of various forms of mental, emotional and physical stress. By contrast, blood pressure varies widely when the autonomic nervous system is absent or when key mechanisms that govern it are destroyed. However, 24 h mean arterial pressure is still surprisingly normal under these conditions. Thus, the dominant idea has been that the kidney is the main long-term regulator of blood pressure and the autonomic nervous system is important in short-term regulation. However, this 'renocentric' scheme can be challenged by observations in humans showing that there is a high degree of individual variability in elements of the autonomic nervous system. Along these lines, the level of sympathetic outflow, the adrenergic responsiveness of blood vessels and individual haemodynamic patterns appear to exist in a complex, but appropriate, balance in normotension. Furthermore, evidence from animals and humans has now clearly shown that the sympathetic nervous system can play an important role in longer term blood pressure regulation in both normotension and hypertension. Finally, humans with high baseline sympathetic traffic might be at increased risk for hypertension if the 'balance' among factors deteriorates or is lost. In this context, the goal of this review is to encourage a comprehensive rethinking of the complexities related to long-term blood pressure regulation in humans and promote finer appreciation of physiological relationships among the autonomic nervous system, vascular function, ageing, metabolism and blood pressure.

Figure 1. Distribution of mean arterial pressure (A), cardiac output (B) and total peripheral resistance (C) in a conscious dog before and after baro-denervation

Twenty-four hour mean arterial pressure was normal but more variable after baro-denervation. By contrast, both the average values and distribution for cardiac output and total peripheral resistance were normal after baro-denervation. (From Cowley et al. 1973, with permission.)

Figure 2. Effects of electrical stimulation on Ang II hypertension

Left panel shows the effects of baroreflex activation on blood pressure in normal animals and animals administered angiotensin II to evoke hypertension. Electrical stimulation of baroreflexes caused sustained reductions in blood pressure in the control animals but the effects in the animals administered angiotensin II waned over time. Right panel shows effects of chronic electrical stimulation of the carotid sinus (baroreflex activation) on animals before and after renal denervation. The sustained reduction in blood pressure was unaffected by renal denervation. (From Lohmeier et al. 2005, , with permission.)

Figure 3. Blood pressure responses to sodium loading in sham-operated and sinoaortic denervated (SAD) animals

Both 4 and 8% saline drinking water had only modest effects on mean arterial pressure in the sham-operated (SHAM) animals. By contrast, sodium loading after sinoaortic denervation led to marked increases in mean arterial pressure. (From Osborn & Hornfeldt, 1998, with permission.)

Figure 4. MSNA and blood pressure

Left panel shows the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure in males and females below and above 40 years of age. In the younger cohorts there was no relationship between MSNA and mean arterial pressure. By contrast, in those over 40 years of age, increases in MSNA showed some influence on mean arterial pressure. Right panel shows MSNA expressed either as bursts per minute or bursts per 100 heartbeats in middle-aged, normotensive and hypertensive subjects. In these cohorts, there are no dramatic differences in MSNA. (Left panel from Narkiewicz et al. 2005; right panel from Gudbjörnsdóttir et al. 1996, with permission.)

Figure 5. MSNA, cardiac output and adrenergic sensitivity

Left panel shows the relationship between muscle sympathetic nerve activity (in bursts per 100 heart beats) and cardiac output (CO) in normotensive subjects. Individuals with high levels of MSNA tended to have lower levels of cardiac output. Right pane shows the forearm vasoconstrictor responses (ΔFBF; forearm blood flow) to the release of noradrenaline (expressed as arteriovenous difference in NA) evoked by brachial artery administration of tyramine in subjects with low and high levels of MSNA. Subjects with high levels of MSNA showed blunted vasoconstrictor responses to a given level of noradrenaline. These observations help to explain how normotension is maintained in subjects with high levels of MSNA. (Figure from Charkoudian et al. 2005, , with permission.)

Figure 6. Effects of ganglionic blockade on the fall in systolic blood pressure (ΔSBP) in lean subjects, obese subjects and obese subjects with hypertension (HTA)

Obese subjects with hypertension also had elevated muscle sympathetic nerve activity. Note the evidence for increased autonomic support of blood pressure in obese hypertensive subjects. (Figure from Shibao et al. 2007, with permission.)

Figure 7. Effects of chronic electrical stimulation in carotid sinus nerve in a human patient with resistant hypertension

During 28 min of dose–response testing, blood pressure fell from ~225/110 to ~170/100 mmHg. The stimulator was turned off for 9 min and blood pressure rose. During 4 h of observation in the laboratory, blood pressure was lower during stimulation. With 3 days of treatment (far right), sustained reductions in blood pressure were seen in this patient who was resistant to multiple combinations to drug therapy. (From Mohaupt et al. 2007, with permission.)