Elevated renal perfusion pressure does not contribute to natriuresis induced by isotonic saline infusion in freely moving dogs

Seeliger, Erdmann; Andersen, Jens V.; Bie, Peter; Reinhardt, H. W.

doi:10.1113/jphysiol.2004.066670

Cited by 10 publications

(20 citation statements)

References 35 publications

(77 reference statements)

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“…There is no doubt that changes in renal arterial perfusion pressure can strongly affect renal salt and water excretion (Guyton, 1980) and that this has major effects on blood pressure and other cardiovascular variables. But, as Bie and others have shown convincingly (Seeliger et al 2004; Bie, 2009), there also are powerful factors regulating sodium excretion that appear to function independent of any changes in renal arterial perfusion pressure. By demonstrating that a model based exclusively on these latter factors (along with other standard circulatory features) can reproduce the shift in the pressure–natriuresis relationship always observed in hypertensive individuals, we emphasize that such a shift per se cannot be taken as evidence of a functional alteration in the pressure–natriuresis mechanism (i.e.…”

Section: Discussionmentioning

confidence: 97%

“…SE2: sodium intake–natriuresis mechanism It is a well‐established empirical fact that urinary sodium excretion is tightly regulated to match sodium intake under steady‐state conditions, but critical gaps remain in our understanding of the mechanisms responsible (Bie, 2009). Although renal perfusion pressure (which is equivalent to mean arterial pressure in the normal intact circulation) is indisputably one very important factor influencing renal sodium excretion, a necessary link between mean arterial pressure and sodium excretion has been questioned (Seeliger et al 2004; Bie, 2009). In particular, at steady‐state, healthy kidneys are capable of excreting a wide range of sodium intakes with no measureable change in mean arterial pressure.…”

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confidence: 99%

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A new conceptual paradigm for the haemodynamics of salt‐sensitive hypertension: a mathematical modelling approach

Averina

Othmer

Fink

et al. 2012

The Journal of Physiology

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Key points• Causes of chronically-elevated arterial blood pressure (hypertension) are highly debated and difficult to study experimentally. Mathematical models can help elucidate potential causes of hypertension that are experimentally inaccessible.• All current models are based on one key assumption that long-term regulation of blood pressure depends on sodium excretion by the kidney. This assumption leads to the conclusion that hypertension must be caused by kidney dysfunction.• However, some experimental evidence suggests that kidney function can remain normal and that instead elevated neural activity to the vasculature causes hypertension.• We developed a mathematical model where sodium excretion is independent of blood pressure and neural activation to the vasculature triggers hypertension. Our model reproduces the solutions of earlier models, yet still shows the empirically well-established correlation between changes in sodium excretion and blood pressure. • Thus the model provides a novel platform for studying non-kidney based theories of hypertension aetiology.Abstract A conceptually novel mathematical model of neurogenic angiotensin II-salt hypertension is developed and analysed. The model consists of a lumped parameter circulatory model with two parallel vascular beds; two distinct control mechanisms for both natriuresis and arterial resistances can be implemented, resulting in four versions of the model. In contrast with the classical Guyton-Coleman model (GC model) of hypertension, in the standard version of our new model natriuresis is assumed to be independent of arterial pressure and instead driven solely by sodium intake; arterial resistances are driven by increased sympathetic nervous system activity in response to the elevated plasma angiotensin II and increased salt intake (AngII-salt). We compare the standard version of our new model against a simplified Guyton-Coleman model in which natriuresis is a function of arterial pressure via the pressure-natriuresis mechanism, and arterial resistances are controlled via the whole-body autoregulation mechanism. We show that the simplified GC model and the new model correctly predict haemodynamic and renal excretory responses to induced changes in angiotensin II and sodium inputs. Importantly, the new model reproduces the pressure-natriuresis relationship -the correlation between arterial pressure and sodium excretion -despite the assumption of pressure-independent natriuresis. These results show that our model provides a conceptually new alternative to Guyton's theory without contradicting observed haemodynamic changes or pressure-natriuresis relationships. Furthermore, the new model supports the view that hypertension need not necessarily have a renal aetiology and that long-term arterial pressure could be determined by sympathetic nervous system activity without involving the renal sympathetic nerves.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

A new conceptual paradigm for the haemodynamics of salt‐sensitive hypertension: a mathematical modelling approach

Averina

Othmer

Fink

et al. 2012

The Journal of Physiology

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“…However, under normal conditions, acute sodium loading may cause natriuresis without any change in blood pressure (27,30), and occasionally a significant natriuretic response to slow sodium loading may develop concomitant with a significant, albeit minute, decrease in arterial pressure (2). In addition, it has been shown in freely moving dogs that the natriuretic response to more robust sodium loading remains intact when changes in renal arterial pressure are prevented by a servocontrol mechanism (31). A substantial number of experimental results, therefore, seem to demonstrate that mechanisms serving to maintain sodium balance can be activated without any increase in (renal) arterial blood pressure.…”

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confidence: 98%

Chronic activation of plasma renin is log-linearly related to dietary sodium and eliminates natriuresis in response to a pulse change in total body sodium

Kjølby¹,

Bie²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Responses to acute sodium loading depend on the load and on the level of chronic sodium intake. To test the hypothesis that an acute step increase in total body sodium (TBS) elicits a natriuretic response, which is dependent on the chronic level of TBS, we measured the effects of a bolus of NaCl during different low-sodium diets spanning a 25-fold change in sodium intake on elements of the renin-angiotensin-aldosterone system (RAAS) and on natriuresis. To custom-made, low-sodium chow (0.003%), NaCl was added to provide four levels of intake, 0.03-0.75 mmol.kg(-1).day(-1) for 7 days. Acute NaCl administration increased PV (+6.3-8.9%) and plasma sodium concentration (~2%) and decreased plasma protein concentration (-6.4-8.1%). Plasma ANG II and aldosterone concentrations decreased transiently. Potassium excretion increased substantially. Sodium excretion, arterial blood pressure, glomerular filtration rate, urine flow, plasma potassium, and plasma renin activity did not change. The results indicate that sodium excretion is controlled by neurohumoral mechanisms that are quite resistant to acute changes in plasma volume and colloid osmotic pressure and are not down-regulated within 2 h. With previous data, we demonstrate that RAAS variables are log-linearly related to sodium intake over a >250-fold range in sodium intake, defining dietary sodium function lines that are simple measures of the sodium sensitivity of the RAAS. The dietary function line for plasma ANG II concentration increases from theoretical zero at a daily sodium intake of 17 mmol Na/kg (intercept) with a slope of 16 pM increase per decade of decrease in dietary sodium intake.

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“…A total of 81 chronically instrumented female Beagles, about 2 years of age, and weighing 12-16 kg, were studied by standardized methods described in detail in previous papers (10,24,29,30,34,36,37). On completion of the experiments, implants were removed and the dogs were given to suitable private individuals.…”

Section: Methodsmentioning

confidence: 99%

Are large amounts of sodium stored in an osmotically inactive form during sodium retention? Balance studies in freely moving dogs

Seeliger¹,

Ladwig²,

Reinhardt³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Alterations in total body sodium (TBSodium) that covered the range from moderate deficit to large surplus were induced by 10 experimental protocols in 66 dogs to study whether large amounts of Na+ are stored in an osmotically inactive form during Na+ retention. Changes in TBSodium, total body potassium (TBPotassium), and total body water (TBWater) were determined by 4-day balance studies. A rather close correlation was found between individual changes in TBSodium and those in TBWater (r2 = 0.83). Changes in TBSodium were often accompanied by changes in TBPotassium. Taking changes of both TBSodium and TBPotassium into account, the correlation with TBWater changes became very close (r2 = 0.93). The sum of changes in TBSodium and TBPotassium was accompanied by osmotically adequate TBWater changes, and plasma osmolality remained unchanged. Calculations reveal that even moderate TBSodium changes often included substantial Na+/K+ exchanges between extracellular and cellular space. The results support the theory that osmocontrol effectively adjusts TBWater to the body's present content of the major cations, Na+ and K+, and do not support the notion that, during Na+ retention, large portions of Na+ are stored in an osmotically inactive form. Furthermore, the finding that TBSodium changes are often accompanied by TBPotassium changes and also include Na+/K+ redistributions between fluid compartments suggests that cells may serve as readily available Na+ store. This Na+ storage, however, is osmotically active, since osmotical equilibration is achieved by opposite redistribution of K+.

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Elevated renal perfusion pressure does not contribute to natriuresis induced by isotonic saline infusion in freely moving dogs

Cited by 10 publications

References 35 publications

A new conceptual paradigm for the haemodynamics of salt‐sensitive hypertension: a mathematical modelling approach

A new conceptual paradigm for the haemodynamics of salt‐sensitive hypertension: a mathematical modelling approach

Chronic activation of plasma renin is log-linearly related to dietary sodium and eliminates natriuresis in response to a pulse change in total body sodium

Are large amounts of sodium stored in an osmotically inactive form during sodium retention? Balance studies in freely moving dogs

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