Comments on Point:Counterpoint: The dominant contributor to systemic hypertension: Chronic activation of the sympathetic nervous system vs. Activation of the intrarenal renin-angiotensin system ACTIVATED INTRARENAL RENIN-ANGIOTENSIN SYSTEM IS CORRELATED WITH HIGH BLOOD PRESSURE IN HUMANS TO THE EDITOR: Dr. Esler (1) states that Dr. Navar did not provide evidence demonstrating that the activation of the intrarenal renin-angiotensin system (RAS) is the primary mechanism of essential hypertension in humans. However, recent clinical studies have provided data supporting the role of the intrarenal RAS in hypertension. Studies by our group (2, 3) and others (4, 5) indicate that urinary angiotensinogen excretion rate provides a novel bi- omarker of the intrarenal RAS. In a cross-sectional study, we reported that urinary angio- tensinogen levels are significantly greater in hypertensive pa- tients not treated with RAS blockers compared with normo- tensive subjects. Moreover, patients treated with RAS blockers exhibit a marked attenuation of this augmentation. However, patients treated with beta-blockers also exhibited high urinary angiotensinogen levels (2). In a population study, we provided another example demonstrating that an activated intrarenal RAS is correlated with high blood pressure in humans. We recruited 251 subjects and collected a single random spot urine sample from each subject. Because urinary angiotensinogen levels are significantly increased in diabetic patients and the use of antihypertensive drugs affects urinary angiotensinogen lev- els, we excluded patients who had diabetes and/or were receiving antihypertensive treatment. Consequently, 190 samples were included for this analysis. Urinary angio- tensinogen levels did not differ with race or sex, but were significantly correlated with systolic and diastolic blood pressure. Moreover, high correlations were shown in men, especially in black men (3). Addition of these recent findings of clinical studies strength- ens the view that the intrarenal RAS is a major contributor to essential hypertension. REFERENCES 1. Esler MD, Lambert EA, Schlaich M, Navar LG. Point:Counterpoint: The dominant contributor to systemic hypertension: Chronic activation of the sympathetic nervous system vs. activation of the intrarenal renin-angioten- sin system. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010. 2. Kobori H, Alper AB, Shenava R, Katsurada A, Saito T, Ohashi N, Urushihara M, Miyata K, Satou R, Hamm LL, Navar LG. Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients. Hypertension 53: 344 –350, 2009. 3. Kobori H, Urushihara M, Xu JH, Berenson GS, Navar LG. Urinary angiotensinogen is correlated with blood pressure in men (Bogalusa Heart Study). J Hypertens 28: 1422–1428, 2010. 4. Lantelme P, Rohrwasser A, Vincent M, Cheng T, Gardier S, Legedz L, Bricca G, Lalouel JM, Milon H. Significance of urinary angiotensinogen in essential hypertension as a function of plasma renin and aldosterone status. J Hypertens 23: 785–792, 2005. 5. Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, Kato A, Nakamura Y, Suzuki F, Hishida A. Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol 18: 1558 –1565, 2007. Hiroyuki Kobori Associate Professor Departments of Medicine and of Physiology Tulane University Health Sciences Center SYMPATHETIC NERVOUS SYSTEM, PLASMA VOLUME, AND HYPERTENSION TO THE EDITOR: Sympathetic activity may be measured by different techniques such as plasma norepinephrine, microneu- rography and spillover (3). A number of studies suggest that chronic activation of the sympathetic nervous system contrib- utes to systemic hypertension (2). On the other hand, there are many carefully controlled studies, where no changes in sym- pathetic activity have been found (1). We studied, for example, plasma norepinephrine and renin in the basal state and after stimulation in a group of untreated patients with essential hypertension (4). Observed values were similar in patients and in controls. Plasma epinephrine concentrations were also sim- ilar, indicating that essential hypertension is not a disease of the mind. The high values of norepinephrine spillover reported by Esler et al. (2) could easily have been detected by 24 h measurements of urine norepinephrine and epinephrine. Again many authors have reported no difference in urine cat- echolamines between patients and controls. There is a charac- teristic difference in plasma volume in patients with pheochro- mocytoma compared with patients with essential hypertension. Patients with pheochromocytoma have a reduced blood volume due to the increase in blood pressure, whereas plasma volume is normal in patients with essential hypertension due to the increase in blood pressure. All these findings and others (5) suggest that essential hypertension is a disease of the kidney and it is not due to chronic activation of the sympathetic nervous system. REFERENCES 1. Christensen NJ. Editorial review: Catecholamines and essential hyperten- sion. Scand J Clin Lab Invest 42: 211–215, 1982. 2. Esler M, Lambert E, Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hyper- tension. J Appl; doi: 10.1152/japplphysiol.00182.2010. 3. Henriksen JH, Christensen NJ. Plasma norepinephrine in humans: limi- tations in assessment of whole body norepinephrine kinetics and plasma clearance. Am J Physiol Endocrinol Physiol 257: E743–E750. 1989. 4. Ibsen H, Christensen NJ, Hollnagel H, Leth A, Kappelgaard AM, Giese J. Plasma noradrenaline concentration in hypertensive and normotensive forty-year-old individuals: relationship to plasma renin concentration. J Clin Lab Invest 40: 333–339, 1980. 5. Navar LG. Counterpoint: Activation of the intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010a. Niels Juel Christensen Professor Herlev University Hospital J Appl Physiol 109: 2003–2014, 2010; doi:10.1152/japplphysiol.01160.2010. Point:Counterpoint Comments 8750-7587/10 Copyright © 2010 the American Physiological Society http://www.jap.org 2003 by 10.220.33.6 on November 10, 2017 http://jap.physiology.org/ Downloaded from