Abstract-Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (26Ϯ1 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored heart rate, thoracic bioimpedance, blood pressure, glomerular filtration rate, and renal blood flow. Ninety minutes after ingestion of the test medication, subjects were tilted to a 45°head-up position, where they remained for an additional 30 minutes. Reboxetine increased supine systolic blood pressure through an increase in cardiac output whereas systemic vascular resistance decreased. Furthermore, reboxetine increased heart rate, particularly with a head-up tilt. Supine plasma renin activity was 0.71Ϯ0.15 ng angiotensin (Ang)/L per mL/h with placebo and 0.36Ϯ0.07 ngAng/L per mL/h with reboxetine (PϽ0.01). Supine plasma Ang II concentrations were also decreased with reboxetine. Both plasma renin activity and Ang II concentrations remained suppressed during head-up tilt. On placebo, renal vascular resistance increased with head-up tilt. The response was abolished with norepinephrine reuptake inhibition. We conclude that norepinephrine reuptake function profoundly influences the distribution of sympathetic activity between the heart, vasculature, and kidney in humans. All of these changes are physiologically relevant because they lead to corresponding changes in organ function. (Hypertension. 2006;48:120-126.)Key Words: sympathetic nervous system Ⅲ norepinephrine Ⅲ renal circulation Ⅲ renin-angiotensin system S ympathetic activity is not evenly distributed among the blood vessels, heart, and kidney. Discordant sympathetic activation of the heart and the kidney may be relevant to common cardiovascular disorders. For example, the postural tachycardia syndrome (POTS) is associated with excessive cardiac sympathetic activity. 1 Decreased renal sympathetic activity in POTS is suggested by hypovolemia together with inappropriately low renin-angiotensin system activity. 2 In contrast, in obese subjects, renal norepinephrine spillover is increased. 3 Sympathetic traffic to the vasculature may also be increased, at least in a subgroup of obese patients. 4,5 Cardiac sympathetic activity is suppressed in obese normotensive persons and is within the normal range in obese hypertensive patients. 6 Yet, the mechanisms regulating sympathetic distribution between the heart and kidney are poorly understood. Norepinephrine reuptake transporter (NET) function may be important in this regard. Acute pharmacological NET blockade reduces sympathetic vasomotor tone 7 and renal norepinephrine spillover in humans. 8 In contrast, cardiac norepinephrine spillover 8 and upright heart rate are substantially increased. 9 Similarly, upright heart rate is increased in patients with genetic NET deficiency....

In healthy subjects, NET inhibition prevents tilt-induced neurally mediated (pre)syncope. Therefore, NET inhibition may be a worthwhile target of drug intervention for larger trials in highly symptomatic patients with neurally mediated syncope.

(1) Introduction: Iron deficiency (ID) contributes to impaired functional performance and reduced quality of life in patients with chronic illnesses. The role of ID in stroke is unclear. The aim of this prospective study was to evaluate the prevalence of ID and to evaluate its association with long-term functional outcome in patients with ischemic stroke. (2) Patients and Methods: 140 patients (age 69 ± 13 years, BMI 27.7 ± 4.6 kg/m², mean ± SD) admitted to a university hospital stroke Unit, with acute ischemic stroke of the middle cerebral artery were consecutively recruited to this observational study. Study examinations were completed after admission (3 ± 2 days after acute stroke) and at one-year follow up (N = 64, 382 ± 27 days after stroke). Neurological status was evaluated according to the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRS). Muscle isometric strength of the non-affected limb was assessed by the maximum handgrip test and knee extension leg test. ID was diagnosed with serum ferritin levels ≤ 100 µg/L (ID Type I) or 100–300 µg/L if transferrin saturation (TSAT) < 20% (ID Type II). (3) Results: The prevalence of ID in acute stroke patients was 48% (N = 67), with about two-thirds of patients (N = 45) displaying ID Type I and one-third (N = 22) Type II. Handgrip strength (HGS) and quadriceps muscle strength were reduced in patients with ID compared to patients without ID at baseline (HGS: 26.5 ± 10.4 vs. 33.8 ± 13.2 kg, p < 0.001 and quadriceps: 332 ± 130 vs. 391 ± 143 N, p = 0.06). One year after stroke, prevalence of ID increased to 77% (p = 0.001). While an improvement of HGS was observed in patients with normal iron status, patients with ID had no improvement in HGS difference (4.6 ± 8.3 vs. −0.7 ± 6.5 kg, p < 0.05). Patients with ID remained with lower HGS compared to patients with normal iron status (28.2 ± 12.5 vs. 44.0 ± 8.6 kg, p < 0.0001). (4) Conclusions: Prevalence of ID was high in patients after acute stroke and further increased one year after stroke. ID was associated with lower muscle strength in acute stroke patients. In patients with ID, skeletal muscle strength did not improve one year after stroke.