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

POINT:COUNTERPOINTComments on Point:Counterpoint: The dominant contributor to systemic hypertension: Chronic activation of the sympathetic nervous system vs. Activation of the intrarenal renin-angiotensin systemComments on Point:Counterpoint: The dominant contributor to systemic hypertension: Chronic activation of the sympathetic nervous system vs. Activation of the intrarenal renin-angiotensin systemPublished Online:01 Dec 2010https://doi.org/10.1152/japplphysiol.01160.2010MoreSectionsPDF (114 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ACTIVATED INTRARENAL RENIN-ANGIOTENSIN SYSTEM IS CORRELATED WITH HIGH BLOOD PRESSURE IN HUMANSHiroyuki Kobori.Author AffiliationsAssociate Professor Departments of Medicine and of Physiology Tulane University Health Sciences Center.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 biomarker of the intrarenal RAS.In a cross-sectional study, we reported that urinary angiotensinogen levels are significantly greater in hypertensive patients not treated with RAS blockers compared with normotensive 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 levels, we excluded patients who had diabetes and/or were receiving antihypertensive treatment. Consequently, 190 samples were included for this analysis. Urinary angiotensinogen 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 strengthens the view that the intrarenal RAS is a major contributor to essential hypertension.REFERENCES1. 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-angiotensin system. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.Google Scholar2. 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.Crossref | PubMed | ISI | Google Scholar3. 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.Crossref | PubMed | ISI | Google Scholar4. 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.Crossref | ISI | Google Scholar5. 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.Crossref | PubMed | ISI | Google ScholarREFERENCES1. 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-angiotensin system. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.Google Scholar2. 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.Crossref | PubMed | ISI | Google Scholar3. 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.Crossref | PubMed | ISI | Google Scholar4. 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.Crossref | ISI | Google Scholar5. 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.Crossref | PubMed | ISI | Google ScholarSYMPATHETIC NERVOUS SYSTEM, PLASMA VOLUME, AND HYPERTENSIONNiels Juel Christensen.Author AffiliationsProfessor Herlev University Hospital.to the editor: Sympathetic activity may be measured by different techniques such as plasma norepinephrine, microneurography and spillover (3). A number of studies suggest that chronic activation of the sympathetic nervous system contributes to systemic hypertension (2). On the other hand, there are many carefully controlled studies, where no changes in sympathetic 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 similar, 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 catecholamines between patients and controls. There is a characteristic difference in plasma volume in patients with pheochromocytoma 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.REFERENCES1. Christensen NJ. Editorial review: Catecholamines and essential hypertension. Scand J Clin Lab Invest 42: 211–215, 1982.Crossref | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Henriksen JH , Christensen NJ. Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance. Am J Physiol Endocrinol Physiol 257: E743–E750. 1989.Link | ISI | Google Scholar4. 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.Crossref | ISI | Google Scholar5. 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.ISI | Google ScholarREFERENCES1. Christensen NJ. Editorial review: Catecholamines and essential hypertension. Scand J Clin Lab Invest 42: 211–215, 1982.Crossref | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Henriksen JH , Christensen NJ. Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance. Am J Physiol Endocrinol Physiol 257: E743–E750. 1989.Link | ISI | Google Scholar4. 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.Crossref | ISI | Google Scholar5. 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.ISI | Google ScholarSYSTEMIC HYPERTENSION—A “RATOLOGIST” POINT OF VIEWClaude Julien.Author AffiliationsPhysiology University Lyon 1, France.to the editor: It is reinvigorating to see that the debate on the pathophysiology of essential hypertension comes back into center stage, largely owing to the recent discoveries by the Professor Esler's group (2). Evidence from rat models of essential hypertension can be taken to support both contentions (2, 6). An exhaustive review of the literature should include findings in the Lyon strain of genetically hypertensive (LH) rats. In this strain, it was found that early surgical denervation of the kidneys had minimal effects on adult blood pressure (1). It was also shown that neonatal chemical sympathectomy did not prevent hypertension and left ventricular hypertrophy in LH rats (5). By contrast, an early chronic treatment with an ACE inhibitor fully prevented the development of hypertension in LH rats. Furthermore, in ACE-blocked LH rats, a 4-wk infusion of angiotensin II, but not of noradrenaline, restored hypertension (4). Finally, it is of note that the renal and circulating renin-angiotensin system was found to be less active and less reactive (to both changes in renal perfusion pressure and β-adrenoceptor stimulation) in LH rats than in their normotensive controls (3). In LH rats, therefore, the renal renin secretion, although depressed, is still inappropriate considering the strong dependency of their blood pressure on the renin-angiotensin system. I would like to suggest that, while there might be different “dominant contributors” to high blood pressure in different strains of spontaneously hypertensive rats, this might also be the case in subgroups of hypertensive patients.REFERENCES1. Boussairi EH , Julien C , Ducher M , Barrès C , Vincent M , Sassard J. Renal denervation does not prevent hypertension in Lyon hypertensive rats. Am J Physiol Regul Integr Comp Physiol 261: R20–R255, 1991.Link | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Julien C , Bertolino S , Medeiros IA , Barrès C , Sassard J. Renin secretion in Lyon hypertensive rats. Clin Exp Hypertens 19: 699–711, 1997.Crossref | ISI | Google Scholar4. Lantelme P , Lo M , Luttenauer L , Sassard J. Pivotal role of the renin- angiotensin system in Lyon hypertensive rats. Am J Physiol Regul Integr Comp Physiol 273: R1793–R1799, 1997.Link | ISI | Google Scholar5. Lo M , Julien C , Barrès C , Boomsma F , Cerutti C , Vincent M , Sassard J. Blood pressure maintenance in hypertensive sympathectomized rats. I. Adrenal medullary catecholamines. Am J Physiol Regul Integr Comp Physiol 261: R1045–R1051, 1991.Link | ISI | Google Scholar6. 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.ISI | Google ScholarREFERENCES1. Boussairi EH , Julien C , Ducher M , Barrès C , Vincent M , Sassard J. Renal denervation does not prevent hypertension in Lyon hypertensive rats. Am J Physiol Regul Integr Comp Physiol 261: R20–R255, 1991.Link | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Julien C , Bertolino S , Medeiros IA , Barrès C , Sassard J. Renin secretion in Lyon hypertensive rats. Clin Exp Hypertens 19: 699–711, 1997.Crossref | ISI | Google Scholar4. Lantelme P , Lo M , Luttenauer L , Sassard J. Pivotal role of the renin- angiotensin system in Lyon hypertensive rats. Am J Physiol Regul Integr Comp Physiol 273: R1793–R1799, 1997.Link | ISI | Google Scholar5. Lo M , Julien C , Barrès C , Boomsma F , Cerutti C , Vincent M , Sassard J. Blood pressure maintenance in hypertensive sympathectomized rats. I. Adrenal medullary catecholamines. Am J Physiol Regul Integr Comp Physiol 261: R1045–R1051, 1991.Link | ISI | Google Scholar6. 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.ISI | Google ScholarSYSTEMIC HYPERTENSION—INVOLVEMENT OF THE CNS TO THIS COMPLEX PUZZLEThiago S. Moreira.Author AffiliationsAssistant Professor Ana C. Takakura Vagner R. Antunes Institute of Biomedical Science University of São Paulo.to the editor: It has long been established that the two major contributors for systemic hypertension are the intrarenal mechanisms and the chronic activation of sympathetic nervous system (SNS) (1, 2). Both ideas were well discussed by Esler and Navar in the present issue of the Journal of Applied Physiol. However, it is important to consider that the central nervous system (CNS) highly contributes to systemic hypertension not only by controlling the sympathetic outflow specifically to renal territory but also to distinct territories, such as splanchnic, hindlimb, and cardiac that play a major role on regulation of vascular resistance and cardiac function (3). The precise mechanisms by which CNS regulates blood pressure (BP) are complex and remain to be discovered. Strong evidence has shown that manipulation of specific autonomic brain regions (hypothalamus, RVLM, and NTS) produces sustained BP and SNS changes in hypertension (3, 4, 5). Besides, it is also necessary to fit a new piece to this complex puzzle, with regards to neurochemical changes induced by proinflamatory cytokines in the hypothalamic-brain stem circuitry, which is linked to the control of the SNS that may lead to significant alterations in BP. Although we acknowledge the fact that the kidney plays a critical role in the long-term control of BP and the chronic activation of SNS is an important contributor to systemic hypertension, we conceive that new paradigms have to be taken into consideration to unravel the complexity of central modulation in the development and/or maintenance of high BP within the context of recent advances in cardiovascular and neuroscience research.REFERENCES1. Esler M , Lambert L , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar2. 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.ISI | Google Scholar3. Osborn JW. Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney. Clin Exp Pharmacol Physiol 32: 384–393, 2005.Crossref | PubMed | ISI | Google Scholar4. Moreira TS , Takakura AC , Colombari E , Menani JV. Antihypertensive effects of central ablatins in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 296: R1797–R1806, 2009.Link | ISI | Google Scholar5. Paton JF , Raizada MK. Neurogenic hypertension. Exp Physiol 95: 569–571, 2010.Crossref | ISI | Google ScholarREFERENCES1. Esler M , Lambert L , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar2. 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.ISI | Google Scholar3. Osborn JW. Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney. Clin Exp Pharmacol Physiol 32: 384–393, 2005.Crossref | PubMed | ISI | Google Scholar4. Moreira TS , Takakura AC , Colombari E , Menani JV. Antihypertensive effects of central ablatins in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 296: R1797–R1806, 2009.Link | ISI | Google Scholar5. Paton JF , Raizada MK. Neurogenic hypertension. Exp Physiol 95: 569–571, 2010.Crossref | ISI | Google ScholarCHRONIC ACTIVATION OF SYMPATHETIC NERVOUS SYSTEM AND SYSTEMIC HYPERTENSION—STRESS SHOWS THE WAYMarco A. P. Fontes.Author AffiliationsAssociate Professor Carlos H. Xavier Dept. of Physiology Federal University of Minas Gerais.to the editor: In the Counterpoint rebuttal, Dr. Navar (5) states that “the divergence of opinion is whether singularly increased sympathetic nervous system activity, independent of activation of renin-angiotensin system (RAS), can result in sustained hypertension.” Despite the fact that it is difficult to dissociate increased sympathetic activity from activation of the RAS (3), the level of activity innervating different target organs can be non-uniformly changed, thus leading to different patterns according to particular stimulus (2). This is the case for mental stress, as pointed by Esler and colleagues (4). For example, mental stress in humans causes robust increase in muscle sympathetic nerve activity (1) that certainly may have chronic cardiovascular implications. We recently demonstrated that the control of sympathetic output by the dorsomedial hypothalamus (DMH), a critical nucleus for the cardiovascular response to emotional stress, is functionally asymmetric. Indeed, DMH exerts a strong influence over sympathetic activity to the kidneys and this outflow is predominantly lateralized (6). Central asymmetries also distinctly influence cardiac function, supporting the plausible hypothesis that central mechanisms differentially affect hemodynamic. Therefore, altered renal physiology is critical for the development of systemic hypertension, but this possibly results from chronic secondary activation of renal sympathetic outflow. Nowadays, the impact of psychosocial stress has undoubtedly been a challenge for the cardiovascular system and body homeostasis. Revealing the relevant central mechanisms involved in controlling sympathetic activity to acute and chronic stress is a critical step to understand the pathogenesis of essential hypertension.REFERENCES1. Carter JR , Kupiers NT , Ray CA. Neurovascular responses to mental stress. J Physiol 564: 321–327, 2005.Crossref | PubMed | ISI | Google Scholar2. Dampney RA , Coleman MJ , Fontes MA , Hirooka Y , Horiuchi J , Li YW , Polson JW , Potts PD , Tagawa T. Central mechanisms underlying short- and long-term regulation of the cardiovascular system. Clin Exp Pharmacol Physiol 29: 261–268, 2002.Crossref | PubMed | ISI | Google Scholar3. DiBona GF. Neural control of the kidney: functionally specific renal sympathetic nerve fibers. Am J Physiol Regul Integr Comp Physiol 279: R1517–R1524, 2000.Link | ISI | Google Scholar4. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar5. Navar L. Counterpoint: Activation of intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010a.ISI | Google Scholar6. Xavier CH , Nalivaiko E , Beig MI , Menezes GB , Cara DC , Campagnole-Santos MJ , Fontes MA. Functional asymmetry in the descending cardiovascular pathways from dorsomedial hypothalamic nucleus. Neuroscience 164: 1360–1368, 2009.Crossref | PubMed | ISI | Google ScholarREFERENCES1. Carter JR , Kupiers NT , Ray CA. Neurovascular responses to mental stress. J Physiol 564: 321–327, 2005.Crossref | PubMed | ISI | Google Scholar2. Dampney RA , Coleman MJ , Fontes MA , Hirooka Y , Horiuchi J , Li YW , Polson JW , Potts PD , Tagawa T. Central mechanisms underlying short- and long-term regulation of the cardiovascular system. Clin Exp Pharmacol Physiol 29: 261–268, 2002.Crossref | PubMed | ISI | Google Scholar3. DiBona GF. Neural control of the kidney: functionally specific renal sympathetic nerve fibers. Am J Physiol Regul Integr Comp Physiol 279: R1517–R1524, 2000.Link | ISI | Google Scholar4. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar5. Navar L. Counterpoint: Activation of intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010a.ISI | Google Scholar6. Xavier CH , Nalivaiko E , Beig MI , Menezes GB , Cara DC , Campagnole-Santos MJ , Fontes MA. Functional asymmetry in the descending cardiovascular pathways from dorsomedial hypothalamic nucleus. Neuroscience 164: 1360–1368, 2009.Crossref | PubMed | ISI | Google ScholarTHE ROLE OF THE SYMPATHETIC NERVOUS SYSTEM—INFLUENCES OF SEX AND AGINGNisha Charkoudian.Author AffiliationsAssociate Professor of Physiology Emma C. Hart Jill N. Barnes Michael J. Joyner Mayo Clinic.to the editor: We congratulate Professors Esler and Navar on their excellent Point:Counterpoint on this long-running debate (2, 6). Our own perspectives lead us to support the primary importance of the sympathetic nervous system in human arterial pressure regulation. Along these lines, we offer additional thoughts in support of sympathetic neural mechanisms in control of arterial pressure in humans. Chronic levels of sympathetic nerve activity (SNA) are highly variable among individuals but reproducible in a given individual. In our recent studies, we demonstrated that this inter-individual variability in SNA is an important component of an integrated balance that includes cardiac output, vascular responsiveness, and sex differences (potentially via β-adrenergic receptors) that contributes to the long-term level of arterial pressure (1, 3). Thus it is interesting to note that, at least for men, SNA is inversely associated with the fall in blood pressure seen during ganglionic blockade (4). Observations from our laboratory and others suggest that, in aging humans, basal SNA becomes a crucial factor in determining the level of arterial pressure at rest (5). This may be particularly evident in women: β-adrenergic-mediated vasodilation appears to blunt the pressor effects of SNA in young women (3), but may not offset these effects in post-menopausal women. Similar arguments may exist for nitric oxide-mediated vasodilation counteracting the pressor effects of SNA. In this context, the loss of nitric oxide bioavailability in conjunction with high levels of SNA might contribute to the genesis of hypertension.REFERENCES1. Charkoudian N , Joyner MJ , Sokolnicki LA , Johnson CP , Eisenach JH , Dietz NM , Curry TB , Wallin BG. Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans. J Physiol 572: | PubMed | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Hart , Charkoudian N , Wallin , Curry TB , Eisenach JH , Joyner differences in sympathetic for human blood pressure regulation. Hypertension 53: 2009.Crossref | PubMed | ISI | Google Scholar4. , , , J , JR , RA , autonomic support of arterial blood pressure with in | PubMed | ISI | Google Scholar5. K , , Kato M , , L , between blood pressure, and sympathetic nerve Hypertension 2005.Crossref | PubMed | ISI | Google Scholar6. 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.ISI | Google ScholarREFERENCES1. Charkoudian N , Joyner MJ , Sokolnicki LA , Johnson CP , Eisenach JH , Dietz NM , Curry TB , Wallin BG. Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans. J Physiol 572: | PubMed | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; doi: 10.1152/japplphysiol.00182.2010.ISI | Google Scholar3. Hart , Charkoudian N , Wallin , Curry TB , Eisenach JH , Joyner differences in sympathetic for human blood pressure regulation. Hypertension 53: 2009.Crossref | PubMed | ISI | Google Scholar4. , , , J , JR , RA , autonomic support of arterial blood pressure with in | PubMed | ISI | Google Scholar5. K , , Kato M , , L , between blood pressure, and sympathetic nerve Hypertension 2005.Crossref | PubMed | ISI | Google Scholar6. 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.ISI | Google S. the editor: (2, 5) mechanisms of primary hypertension and the of the of the sympathetic nervous and in chronic blood pressure regulation. This on the than the regulation of such as blood pressure, use such as stimulation and or and of results by these not into of of not such as this Point:Counterpoint such is regulation via regulation of via activation of can the role of particular in regulation of a variable such as blood pressure. The is The system is a in regulation of blood pressure and and the sympathetic nervous system is a in regulation of blood pressure and Because of blood pressure may or may not be correlated with or sympathetic nervous correlations would on the status of the other the of blood pressure, does hypertension The might from brain regulation of the renal function DiBona GF. kidney. between renal sympathetic nerves and the renin-angiotensin system in the control of renal Hypertension | PubMed | ISI | Google Scholar2. Esler M , Lambert E , Schlaich M. Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol; | Google Scholar3. models of stress, and acute and chronic disease. | PubMed | ISI | Google Scholar4.