Stroke is the fourth leading cause of death in the United States and the second most common cause of death worldwide; stroke is also the leading cause of long-term disability worldwide. It is clear that the consequences of cerebral ischemia reach beyond the brain into the periphery, and a significant number of stroke related deaths are the result of conditions that develop poststroke in the periphery. The two leading causes of non-neurogenic death poststroke are cardiac abnormalities and infections. Changes in autonomic nervous system function that favor increased sympathetic nervous system activity and reduced parasympathetic nervous system activity appear to be causative factors in both conditions. Here, we review the evidence that sympathetic nervous system activity increases and parasympathetic nervous system activity declines poststroke. We discuss effects of autonomic dysfunction on cardiac arrhythmias and heart rate variability. Finally, we discuss the evidence supporting a role for autonomic dysfunction in the increased incidence of infection poststroke. Although the death rate from stroke is declining in the United States, the incidence of stroke is not. With more patients surviving the initial ischemic event it is important that we broaden our understanding of the chronic effects of stroke on the human condition.

Aldosterone has been linked to the deleterious cardiovascular effects of obesity in humans. The association of aldosterone with obesity in rodents is less well defined, particularly in models of diet-induced obesity. We hypothesized that adrenal aldosterone production and aldosterone synthase expression would be increased in rats with obesity-induced hypertension. Male Sprague Dawley rats were fed a high-fat (HF: 36% fat) or control diet from 3 wk of age, and mean arterial pressure (MAP) was measured by telemetry. MAP was increased after 4 wk of HF diet; this was 6 wk before changes in body weight. Mineralocorticoid receptor antagonism did not prevent the HF-induced increase in MAP. After 17 wk on the diets, HF rats had increased body and fat weights (abdominal and epididymal) and were insulin resistant (Homeostasis Model Assessment index: 3.53 ± 0.43 vs. 8.52 ± 1.77; control vs. HF, P < 0.05). Plasma aldosterone levels were increased in the HF rats (64.14 ± 14.96 vs. 206.25 ± 47.55 pg/ml; control vs. HF, P < 0.05). This occurred independently of plasma renin activity (4.8 ± 0.92 vs. 4.73 ± 0.66 ng/ml/h, control vs. HF). The increase in aldosterone was accompanied by a 2-fold increase in adrenal aldosterone synthase mRNA expression and zona glomerulosa hypertrophy. Rats were also studied after 8 wk of HF diet, a time when MAP, but not body weight, was increased. At this time plasma aldosterone was unchanged but plasma renin activity was increased (4.4 ± 0.5 vs. 8.1 ± 1.3 ng/ml/h; control vs. HF, P < 0.05). These studies suggest that rats fed a HF diet from weaning may be a useful model for studying obesity-associated hyperaldosteronism.

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The purpose of this study was to determine whether genetically obese Zucker rats have higher arterial pressures than lean littermates on normal and high sodium intakes. Mean arterial pressure was directly measured in chronically instrumented Zucker rats (six lean [weight, 345.8 +/- 8.0 g] and five obese [529.0 +/- 6.2 g]) for 2 weeks on both a normal (2 meq sodium/day) and high (6 meq sodium/day) sodium intake (7 days each). In addition, daily heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, and weekly fasting plasma insulin levels were measured. Obese rats exhibited significantly lower heart rate and greater water intake and urine output compared with lean rats whether maintained on control or high sodium intakes. Urinary sodium excretion, however, was identical in lean and obese rats throughout the experiment. Fasting plasma insulin levels in obese rats were seven times greater than those in lean rats. When the rats were maintained on a 2 meq/day sodium intake, mean arterial pressures obtained from the two groups were similar: 103 +/- 1 versus 106 +/- 1 mm Hg (lean versus obese). An increase in sodium intake did not significantly affect mean arterial pressure in either group: 101 +/- 1 versus 105 +/- 1 mm Hg (lean versus obese). These results indicate that at 12-14 weeks of age, male obese Zucker rats do not exhibit higher resting arterial pressures than lean littermates when maintained on normal or high sodium intake.

Evidence has accumulated during the past several decades, strongly suggesting that abnormalities of the sympathetic nervous system contribute to the development and maintenance of multiple disease states, including hypertension, heart failure, diabetes mellitus, sleep apnea, kidney disease, and atrial fibrillation. 1 The renal nerves have been identified as important contributors to the development of hypertension in both experimental animals and humans.2 Patients with essential hypertension and other disease states often have increased efferent sympathetic drive to the kidneys as demonstrated by elevated rates of renal norepinephrine spillover.1,2 In addition to increased renal efferent nerve activity, there is indirect evidence for increased renal afferent activity in patients with essential hypertension.3 Nonselective surgical sympathectomy has been effectively used as a treatment for severe hypertension, 4 with a remarkable difference in outcomes at 5 years of follow-up. Recently developed endovascular catheter technology has allowed selective denervation of the human kidney using radiofrequency (RF) energy delivered via the renal artery lumen.5 Although the initial clinical trials with this minimally invasive technique have documented the safety and efficacy of such an approach, critical questions have been raised pertaining to long-term safety, mechanisms of action, appropriate patient selection, reductions in ambulatory blood pressure (BP), definition and level of responder rates, need for identification of characteristics that predict nonresponse, phenomenon of a delayed response, and several others. 6 Here, we address several of these key questions. What Are the Mechanisms Responsible for a Decrease in BP After RDN?Catheter-based renal nerve ablation interrupts both efferent and afferent nerves (Figure 1). It is well established that activation of renal sympathetic efferents can decrease renal blood flow, increase tubular sodium and water reabsorption, and increase renin release. 2 However, there is emerging evidence that renal afferent signaling may be as important as renal efferent activity in elevating BP. Activation of renal afferents can cause a reflex increase in sympathetic tone to the kidneys and other organs. 7 Intrarenal infusion of bradykinin in conscious rats 8 or intrarenal infusion of adenosine in conscious dogs with unilateral nephrectomy 9 causes an immediate increase in BP that was abolished by surgical renal denervation (RDN). A role for renal afferents in rats with renovascular hypertension was indicated by a significant drop in BP after dorsal rhizotomy (T8 or T10 to L2) to exclusively interrupt afferent fibers. 10There is also evidence that renal afferents play a role in mediating an increase in sympathetic tone in humans. In 25 patients with treatment-resistant hypertension, RDN significantly decreased multi-and single-unit muscle sympathetic nerve activity at 3-month follow-up, which was accompanied by a significant reduction in BP.11 More recently, it was shown that the reduct...