scholarly journals Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

2012 ◽  
Vol 113 (10) ◽  
pp. 1652-1658 ◽  
Author(s):  
Thomas E. Lohmeier ◽  
Radu Iliescu
Keyword(s):  
Arterial Pressure ◽  
Clinical Investigation ◽  
Dominant Role ◽  
Experimental Studies ◽  
Peripheral Resistance ◽  
Sympathetic Outflow ◽  
Excretory Function ◽  
Central Sympathetic Outflow ◽  
Renal Excretory Function

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure.

Recent insights into the interactions between the baroreflex and the kidneys in hypertension

2005 ◽  
Vol 288 (4) ◽  
pp. R828-R836 ◽  
Author(s):  
Thomas E. Lohmeier ◽  
Drew A. Hildebrandt ◽  
Susan Warren ◽  
Paul J. May ◽  
J. Thomas Cunningham
Keyword(s):  
Arterial Pressure ◽  
Experimental Studies ◽  
Secondary Hypertension ◽  
Experimental Models ◽  
Renal Nerves ◽  
Excretory Function ◽  
Clinical Hypertension ◽  
Theoretical Evidence

Recent findings in chronically instrumented animals challenge the classic concept that baroreflexes do not play a role in the chronic regulation of arterial pressure. As alterations in renal excretory function are of paramount importance in the chronic regulation of arterial pressure, several of these recent studies have focused on the long-term interactions between the baroreflex and the kidneys during chronic perturbations in arterial pressure and body fluid volumes. An emerging body of evidence indicates that the baroreflex is chronically activated in several experimental models of hypertension, but in most cases, the duration of these studies has not exceeded 2 wk. Although these studies suggest that the baroreflex may play a compensatory role in attenuating the severity of the hypertension, possibly even in primary hypertension with uncertain causes of sympathetic activation, there has been only limited assessment of the quantitative importance of this interaction in the regulation of arterial pressure. In experimental models of secondary hypertension, baroreflex suppression of renal sympathetic nerve activity is sustained and chronically promotes sodium excretion. This raises the possibility that the renal nerves may be the critical efferent link for baroreceptor-induced suppression of central sympathetic output through which long-term compensatory reductions in arterial pressure are produced. This contention is supported by strong theoretical evidence but must be corroborated by experimental studies. Finally, although it is now clear that pressure-induced increases in baroreflex activity persist for longer periods of time than previously suggested, studies using new tools and novel approaches and extending beyond 2 wk of hypertension are needed to elucidate the true role of the baroreflex in the pathogenesis of clinical hypertension.

Haemodynamic and Blood Volume Studies in Long-Term Haemodialysis Patients, and in Patients with Successfully Transplanted Kidneys

1973 ◽  
Vol 45 (s1) ◽  
pp. 155s-157s
Author(s):  
J. Tuckman ◽  
J.-L. Benninger ◽  
F. Reubi
Keyword(s):  
Mean Arterial Pressure ◽  
Cardiac Index ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Peripheral Resistance ◽  
Total Blood Volume ◽  
Total Blood ◽  
Transplanted Kidneys ◽  
Very High

1. Stabilized hypertensive haemodialysis patients, as well as those with normotension, had a greatly elevated cardiac index (CI) that was not due to hypervolemia, but was most likely secondary to their anaemic condition. The hypertension itself was not accompanied by hypervolaemia, but was associated with a relatively very high total peripheral resistance. 2. In eight patients with successfully transplanted kidneys the following results were found. (a) Five were clearly hypertensive and had supine mean arterial pressure between 117 and 143 mmHg. It is noted that they were receiving prednisone at the time of the studies. (b) CI was normal in seven. (c) Total blood volume was normal in all. (d) The presence of wide-open arterio-venous fistulae was not associated with an increase in CI.

Long-term hypotensive effect of beta-agonist in conscious dogs

1988 ◽  
Vol 255 (3) ◽  
pp. H592-H600
Author(s):  
B. S. Nuwayhid ◽  
D. B. Young ◽  
U. Tipayamontri ◽  
J. P. Montani
Keyword(s):  
Renal Function ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Extracellular Fluid ◽  
Hypotensive Effect ◽  
Beta Agonist ◽  
Plasma Protein Concentration ◽  
Conscious Animal

The purpose of this study was to investigate the arterial pressure response to long-term administration of beta-agonists in the chronically instrumented conscious animal model. Chronically instrumented dogs were given intravenous infusions of ritodrine (2 micrograms.kg-1.min-1) for a period of 2 wk. Several cardiovascular and renal parameters were monitored before, during, and after the ritodrine infusion, and renal function curves were constructed. After the 1st wk of infusion, a new steady state was reestablished, and this was characterized by hypotension, reduced plasma protein concentration, elevated cardiac output, expanded extracellular fluid space, and near normal levels of activity of renin-angiotensin-aldosterone systems. The renal function curve during ritodrine infusion shifted to the left with no change in slope. We propose the following: 1) the persistence of hypotension is most probably related to the resetting of the arterial pressure-kidney blood volume servocontrol mechanisms, and 2) the persistent elevation of cardiac output and reduction in peripheral resistance are most probably related to increased oxygen and nutrient demand during beta-agonist infusions.

scholarly journals Experimental histochrome's effect on the renal excretory function

2011 ◽  
Vol 10 (5) ◽  
pp. 101-105 ◽  
Author(s):  
O. S. Talalayeva ◽  
A. Yu. Zharikov ◽  
S. A. Fedoreyev ◽  
Ya. F. Zverev ◽  
V. M. Bryukhanov ◽  
...  
Keyword(s):  
Diuretic Effect ◽  
Water Excretion ◽  
Subcutaneous Injections ◽  
Excretory Function ◽  
Sodium And Potassium ◽  
Renal Excretory Function

The aim of present investigation was to establish possible histochrome's effect on the renal excretory function. During 10 days was being administrated histochrome by subcutaneous injections in dose 10 mg/kg. Every 2 days was being detected daily renal excretions of water, creatinin, sodium and potassium. Long-term histochrome's administration was followed by a fivefold increasing of water excretion and comparable amplification of creatinin. Sodium's and potassium's excretions were increasing to a lesser degree. The revealed histochrome's diuretic effect qualitatively reminds action of diuretic plants, but quantitatively it was compared with thiazid's one.

Critique of a Large-Scale Organ System Model: Guytonian Cardiovascular Model

1975 ◽  
Vol 97 (3) ◽  
pp. 259-265
Author(s):  
K. Sagawa
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Large Scale ◽  
Renal Hypertension ◽  
Experimental Studies ◽  
Oxygen Demand ◽  
Sensitivity Tests ◽  
Vascular Autoregulation

This paper reviews Guyton’s model which is large not only in the number of its components but also in the time scale that it spans. The evolution of this model is explained in three stages. Guyton started with a drastically simplified model of the entire cardiovascular system as a closed hydraulic loop. It accounted for short-term regulations of cardiac output with a special emphasis on the role of blood volume and the vascular capacity. Guyton’s research objective was then directed toward the analysis of longterm regulation of arterial pressure. Two slowly acting mechanisms were considered as particularly important: (1) the marked increase or decrease of urinary output with only slight increase or decrease in arterial pressure (the renal function curve in the Guytonian model) and (2) long-term vascular autoregulation which includes changes in the extent of vascularization as well as constriction or dilation of existing vessels to match the blood flow with the oxygen demand in tissues. This second-stage model explained the transient dynamics and steady equilibrium of renal hypertension. The current version of Guyton’s model incorporates a variety of additional endocrine and neural mechanisms which parametrically control the renal function curve. With the enormous growth, the identification (or estimation) capability of the model is bound to degrade while its use for multiple parameter sensitivity tests expands. The modeller’s group has attempted to minimize the hazards by frequent checks of model predictions with experimental studies. This interactive effort, plus their concern over these long-term regulatory mechanisms, make the Guytonian model a unique venture in modern cardiovascular physiology.

scholarly journals Preeminent role of the cardiorenal axis in the antihypertensive response to an arteriovenous fistula: an in silico analysis

2019 ◽  
Vol 317 (5) ◽  
pp. H1002-H1012
Author(s):  
John S. Clemmer ◽  
W. Andrew Pruett ◽  
Robert L. Hester ◽  
Thomas E. Lohmeier
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Human Physiology ◽  
Natriuretic Peptide ◽  
Critical Role ◽  
Experimental Studies ◽  
Peripheral Resistance ◽  
Uncontrolled Hypertension ◽  
Av Fistula

Percutaneous creation of a small central arteriovenous (AV) fistula is currently being evaluated for the treatment of uncontrolled hypertension (HT). Although the mechanisms that contribute to the antihypertensive effects of the fistula are unclear, investigators have speculated that chronic blood pressure (BP) lowering may be due to 1) reduced total peripheral resistance (TPR), 2) increased secretion of atrial natriuretic peptide (ANP), and/or 3) suppression of renal sympathetic nerve activity (RSNA). We used an established integrative mathematical model of human physiology to investigate these possibilities from baseline conditions that mimic sympathetic overactivity and impaired renal function in patients with resistant HT. After a small fistula was stimulated, there were sustained increases in cardiac output, atrial pressures, and plasma ANP concentration (3-fold), without suppression of RSNA; at 8 wk, BP was reduced 14 mmHg along with a 32% fall in TPR. In contrast, when this simulation was repeated while clamping ANP at baseline BP decreased only 4 mmHg, despite a comparable fall in TPR. Furthermore, when chronic resetting of atrial mechanoreceptors was prevented during the fistula, RSNA decreased 7%, and along with the same threefold increase in ANP, BP fell 19 mmHg. This exaggerated fall in BP occurred with a similar decrease in TPR when compared with the above simulations. These findings suggest that ANP, but not TPR, is a key determinant of long-term BP lowering after the creation of an AV fistula and support a contribution of suppressed RSNA if resetting of the atrial-renal reflex is truly incomplete. NEW & NOTEWORTHY The mechanisms that contribute to the antihypertensive effects of a small arteriovenous (AV) fistula comparable to the size used by the ROX coupler currently in clinical trials are unclear and not readily testable in clinical or experimental studies. The integrative mathematical model of human physiology used in the current study provides a tool for understanding key causal relationships that account for blood pressure (BP) lowering and for testing competing hypotheses. The findings from the simulations suggest that after creation of a small AV fistula increased ANP secretion plays a critical role in mediating long-term reductions in BP. Measurement of natriuretic peptide levels in hypertensive patients implanted with the ROX coupler would provide one critical test of this hypothesis.

Evaluation of whole body autoregulation in conscious dogs

1988 ◽  
Vol 255 (1) ◽  
pp. H44-H52 ◽  
Author(s):  
P. J. Metting ◽  
J. R. Strader ◽  
S. L. Britton
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Systemic Circulation ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Whole Body ◽  
Pharmacological Blockade ◽  
The Relationship

The ability of the systemic circulation to maintain cardiac output during decreases in arterial pressure was evaluated in conscious dogs with intact reflexes (n = 8) and during pharmacological blockade of the autonomic nervous system, angiotensin II formation, and arginine vasopressin (n = 6). Cardiac output was measured electromagnetically, and aortic pressure was controlled via a gravity reservoir connected to a carotid artery. When aortic pressure was decreased in either small steps to approximately 60% of control, or decreased in a single square-wave step to 75% of control and maintained for 2 h, cardiac output decreased to the same or a greater extent in both control and areflexic dogs. Thus total peripheral resistance did not decrease, and autoregulation of the cardiac output did not occur in response to short-term (less than or equal to 2 h) decreases in arterial pressure, even in the absence of the major pressor systems. After long-term (greater than 8 h) decreases in arterial pressure to 75% of control in five dogs with all reflexes intact, significant autoregulation of the cardiac output occurred. The relationship between the gain of blood flow autoregulation and the corresponding values of mixed venous oxygen tension suggests that whole body autoregulation results when oxygen extraction reserve becomes limited.

Graphic format for teaching long-term control of systemic arterial pressure.

1996 ◽  
Vol 270 (6) ◽  
pp. S40
Author(s):  
J J Faber
Keyword(s):  
Cardiac Output ◽  
Steady State ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Systemic Arterial Pressure ◽  
Filling Pressure ◽  
Arterial Blood ◽  
Ventricular Filling Pressure ◽  
Ventricular Filling

Circulatory homeostasis is a difficult notion. The graphic format presented here facilitates the teaching of long-term control of systemic arterial blood pressure and cardiac output. It is based on the view that the following four "function curves" cooperate in long-term regulation: the relation between blood volume and ventricular filling pressure, the relation between ventricular filling pressure and cardiac output, the relation between cardiac output and peripheral resistance, and the relation between arterial pressure and natriuresis. Positioning the function curves in the format presented here clarifies their cooperativity. The distinction between a nonsteady state and a steady state deserves emphasis. Long-term pathophysiology of the circulation is most easily taught on the basis of the assumption that, generally, there will be a steady state. The format clarifies why some known physiological relations are almost impossible to demonstrate in the intact organism, and it discourages explanations of pathophysiology that are not firmly based on physiology.

Haemodynamics during Long-Term Thiazide Treatment in Essential Hypertension: Differences between Responders and Non-Responders

1979 ◽  
Vol 57 (s5) ◽  
pp. 359s-362s ◽  
Author(s):  
P. Van Brummelen ◽  
A. Man In 't Veld ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Cardiac Output ◽  
Essential Hypertension ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Volume ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Haemodynamic Effect ◽  
Pronounced Increase

1. Blood pressure, systemic haemodynamics, plasma volume, renin and aldosterone were measured during placebo treatment and after 1, 4 and 12 weeks of hydrochlorothiazide in 13 patients with uncomplicated essential hypertension. Nine of these patients were also studied after 24 and 36 weeks of treatment. 2. Mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was greater than 10% (responders); four of these were studied for 36 weeks. The remainder were considered non-responders. 3. Hydrochlorothiazide lowered cardiac output. The maximal decrease was observed after 12 weeks of treatment (P < 0·01). In responders this was followed by a return to pretreatment values and a significant decrease in total peripheral resistance, whereas in non-responders cardiac output remained reduced and total peripheral resistance was permanently elevated. 4. Changes in plasma volume, renin and aldosterone were not significantly different in responders and non-responders although non-responders tended to show a greater degree of plasma volume depletion and a more pronounced increase in plasma aldosterone. 5. Thus it is unlikely that the initial decrease in cardiac output is an important determinant of the long-term haemodynamic effect of thiazide diuretics.

scholarly journals A computational analysis of the long-term regulation of arterial pressure

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 208 ◽  
Author(s):  
Daniel A. Beard ◽  
Klas H. Pettersen ◽  
Brian E. Carlson ◽  
Stig W. Omholt ◽  
Scott M. Bugenhagen
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Arterial Pressure ◽  
Dominant Role ◽  
Renin Angiotensin System ◽  
Primary Hypertension ◽  
Model Parameters ◽  
Arterial Blood ◽  
Urine Production

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. capturing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.

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