Role of Kinins in the Control of Renal Papillary Blood Flow, Pressure Natriuresis, and Arterial Pressure

The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.

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Role of cellular L-arginine uptake and nitric oxide production on renal blood flow and arterial pressure regulation

Current Opinion in Nephrology & Hypertension ◽

10.1097/mnh.0b013e32835a6ff7 ◽

2013 ◽

Vol 22 (1) ◽

pp. 45-50 ◽

Cited By ~ 23

Author(s):

Niwanthi W. Rajapakse ◽

David L. Mattson

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Arterial Pressure ◽

Renal Blood Flow ◽

Nitric Oxide Production ◽

Pressure Regulation ◽

Oxide Production ◽

Arginine Uptake ◽

Arterial Pressure Regulation

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Short- and long-term enalapril affect renal medullary hemodynamics in the spontaneously hypertensive rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.1.r10 ◽

1999 ◽

Vol 276 (1) ◽

pp. R10-R16 ◽

Cited By ~ 4

Author(s):

Stephen A. W. Dukacz ◽

Michael A. Adams ◽

Robert L. Kline

Keyword(s):

Blood Flow ◽

Arterial Pressure ◽

Spontaneously Hypertensive Rat ◽

Day Treatment ◽

Ace Inhibition ◽

Spontaneously Hypertensive ◽

Short And Long Term ◽

Pressure Natriuresis ◽

The Relationship

Long-term angiotensin-converting enzyme (ACE) inhibition in the spontaneously hypertensive rat (SHR) resets pressure natriuresis and shifts the relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) to lower levels of arterial pressure. These effects persist after withdrawal of treatment. The purpose of this study was to determine the effect of short- and long-term ACE inhibition on medullary blood flow (MBF). Enalapril (25 mg ⋅ kg−1 ⋅ day−1in drinking water) was given to male SHR from 4 to 14 wk of age. Four weeks after stopping treatment, we measured MBF over a wide range of RAP using laser-Doppler flowmetry in anesthetized rats. Additional rats, either untreated or previously treated for 10 wk, received 3-day enalapril treatment just before the experiment. MAP (mmHg ± SE) was 178 ± 6 ( n = 8), 134 ± 6 ( n = 8), 138 ± 5 ( n = 9), and 111 ± 6 mmHg ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. Total renal blood flow for the groups receiving 3-day treatment was significantly higher when compared with that in rats with an intact renin-angiotensin system. Three-day treatment had no effect on the relationship between RAP and RIHP, whereas that in rats receiving 10-wk treatment was shifted to lower levels of RAP by ∼30 mmHg. Both 10-wk and 3-day treatment independently increased the slope of the RAP versus MBF relationship at values of RAP > 100 mmHg. The slopes in perfusion units/mmHg were 0.12 ± 0.01 ( n = 8), 0.26 ± 0.01 ( n = 8), 0.27 ± 0.01 ( n = 9), and 0.30 ± 0.02 ( n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. These results indicate that the effect of short-term and the persistent effect of long-term enalapril alter renal medullary hemodynamics in a way that may contribute to the resetting of the pressure-natriuresis relationship in treated rats.

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Prostaglandins in the sodium excretory response to altered renal arterial pressure in dogs

AJP Renal Physiology ◽

10.1152/ajprenal.1985.248.1.f8 ◽

1985 ◽

Vol 248 (1) ◽

pp. F8-F14 ◽

Cited By ~ 6

Author(s):

P. K. Carmines ◽

P. D. Bell ◽

R. J. Roman ◽

J. Work ◽

L. G. Navar

Keyword(s):

Blood Flow ◽

Glomerular Filtration Rate ◽

Arterial Pressure ◽

Prostaglandin E2 ◽

Sodium Excretion ◽

Filtration Rate ◽

Systemic Arterial Pressure ◽

Pressure Natriuresis ◽

Excretion Rates ◽

Prostaglandin System

Acute variations in renal arterial pressure are associated with corresponding alterations in absolute and fractional sodium excretion even under conditions of highly efficient autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). Since prostaglandins recently have been implicated in the regulation of sodium excretion, we investigated the hypothesis that the renal prostaglandin system participates in "pressure natriuresis." Anesthetized sodium-replete dogs were subjected to partial carotid artery constriction to elevate systemic arterial pressure. Under these control conditions, sodium excretion was 103 +/- 18 mueq/min (n = 17) and urinary prostaglandin E2 excretion averaged 4.6 +/- 1.5 ng/min (n = 8). Decreases in renal arterial pressure within the auto-regulatory range reduced sodium excretion (2.1%/mmHg) and prostaglandin E2 excretion (1.7%/mmHg), whereas GFR and RBF were not affected. There was a significant correlation between the changes in sodium and prostaglandin E2 excretion rates (r = 0.932, P less than 0.01). In nine dogs treated with indomethacin, sodium excretion was reduced by 70% while GFR and autoregulatory capability were unaffected. There was a marked attenuation of the effect of changes in arterial pressure on sodium excretion, with this parameter exhibiting changes averaging 0.6%/mmHg (P less than 0.001). These observations suggest that the renal prostaglandin system may exert an important influence on the pressure-natriuresis mechanism.

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Renal Response to Nonshocking Hemorrhage: the Role of Intrarenal Shunts

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.193.2.360 ◽

1958 ◽

Vol 193 (2) ◽

pp. 360-364 ◽

Cited By ~ 4

Author(s):

Allan V. N. Goodyer ◽

Louis R. Mattie ◽

Allen Chetrick

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Body Weight ◽

Arterial Pressure ◽

The Body ◽

Arterial Blood ◽

Anesthetized Dogs ◽

Renal Innervation ◽

Aortic Obstruction

In anesthetized dogs, bleeding (1.5–3% of the body weight) was allowed while renal arterial pressure was maintained at constant levels by graded changes of mechanical aortic obstruction. The renal hematocrit decreased, (as measured with I131 albumin and acid hematin, and as compared to the blood hematocrit), primarily as a result of an increased renal plasma volume. These changes are correlated with previously identified alterations of sodium excretion, all independent of renal innervation or arterial blood pressure. It is proposed that hemorrhage may involve an intrarenal redistribution of blood flow favoring diversion of plasma to cell-poor capillaries or to lymphatic spaces.

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NOS inhibition blunts and delays the compensatory dilation in hypoperfused contracting human muscles

Journal of Applied Physiology ◽

10.1152/japplphysiol.00680.2009 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1685-1692 ◽

Cited By ~ 26

Author(s):

Darren P. Casey ◽

Michael J. Joyner

Keyword(s):

Blood Flow ◽

Steady State ◽

Arterial Pressure ◽

Brachial Artery ◽

Muscle Blood Flow ◽

Systemic Arterial Pressure ◽

Balloon Inflation ◽

Forearm Vascular Conductance ◽

Forearm Exercise

We previously demonstrated that skeletal muscle blood flow is restored in the exercising forearm during experimental hypoperfusion via local dilator and/or myogenic mechanisms. This study examined the role of nitric oxide (NO) in the restoration of blood flow to the active muscles during hypoperfusion. Eleven healthy subjects (10 men/1 woman; 25 ± 1 yr of age) performed rhythmic forearm exercise (10% and 20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included baseline, exercise, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local (brachial artery catheter pressure, BAP) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. The exercise bouts were repeated during NG-monomethyl-l-arginine (l-NMMA) infusion (NO synthase inhibition). Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from BF (ml/min) and BAP (mmHg). FBF and FVC fell acutely with balloon inflation during all trials ( P < 0.01). Recovery of FBF and FVC [(inflation − nadir)/(steady-state exercise − nadir)] with l-NMMA administration was reduced during 20% exercise (FBF = 77 ± 7% vs. 88 ± 8%; FVC = 71 ± 8% vs. 90 ± 9%; P < 0.01) but not 10% exercise (FBF = 83 ± 4% vs. 81 ± 5%, P = 0.37; FVC = 75 ± 10% vs. 76 ± 7%; P = 0.44) compared with the respective control trial. The time to steady-state vasodilator response was substantially longer during the l-NMMA trials (10% = 74 ± 4 s vs. 61 ± 6 s; 20% = 53 ± 4 s vs. 41 ± 4 s; P < 0.05). Thus the magnitude and timing of the NO contribution to compensatory dilation during forearm exercise with hypoperfusion was dependent on exercise intensity. These observations suggest that NO is released by contracting muscles or that a portion of the dilation caused by ischemic metabolites is NO dependent.

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Central and peripheral contributors to skeletal muscle hyperemia: response to passive limb movement

Journal of Applied Physiology ◽

10.1152/japplphysiol.00895.2009 ◽

2010 ◽

Vol 108 (1) ◽

pp. 76-84 ◽

Cited By ~ 33

Author(s):

John McDaniel ◽

Anette S. Fjeldstad ◽

Steve Ives ◽

Melissa Hayman ◽

Phil Kithas ◽

...

Keyword(s):

Heart Rate ◽

Blood Flow ◽

Cardiac Output ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Stroke Volume ◽

Limb Movement ◽

Leg Blood Flow ◽

Passive Exercise

The central and peripheral contributions to exercise-induced hyperemia are not well understood. Thus, utilizing a reductionist approach, we determined the sequential peripheral and central responses to passive exercise in nine healthy men (33 ± 9 yr). Cardiac output, heart rate, stroke volume, mean arterial pressure, and femoral blood flow of the passively moved leg and stationary (control) leg were evaluated second by second during 3 min of passive knee extension with and without a thigh cuff that occluded leg blood flow. Without the thigh cuff, significant transient increases in cardiac output (1.0 ± 0.6 l/min, Δ15%), heart rate (7 ± 4 beats/min, Δ12%), stroke volume (7 ± 5 ml, Δ7%), passive leg blood flow (411 ± 146 ml/min, Δ151%), and control leg blood flow (125 ± 68 ml/min, Δ43%) and a transient decrease in mean arterial pressure (3 ± 3 mmHg, 4%) occurred shortly after the onset of limb movement. Although the rise and fall rates of these variables differed, they all returned to baseline values within 45 s; therefore, continued limb movement beyond 45 s does not maintain an increase in cardiac output or net blood flow. Similar changes in the central variables occurred when blood flow to the passively moving leg was occluded. These data confirm the role of peripheral factors and reveal an essential supportive role of cardiac output in the hyperemia at the onset of passive limb movement. This cardiac output response provides an important potential link between the physiology of active and passive exercise.

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Control of sodium excretion in NE-ACTH hypertension: role of pressure natriuresis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.6.r894 ◽

1988 ◽

Vol 255 (6) ◽

pp. R894-R900

Author(s):

L. L. Woods ◽

H. L. Mizelle ◽

J. E. Hall

Keyword(s):

Arterial Pressure ◽

Water Balance ◽

Moderate Hypertension ◽

Significant Rise ◽

Systemic Hypertension ◽

Sodium Balance ◽

Sodium Retention ◽

Background Infusion ◽

Pressure Natriuresis

The purpose of this study was to test the hypothesis that, in the presence of high circulating catecholamines, ACTH decreases renal excretory capability and that its natriuretic effects are caused by increased renal arterial pressure (RAP). In six conscious dogs, norepinephrine (NE, 0.4 micrograms.kg-1.min-1) alone for 5 days caused a small but significant rise in arterial pressure (AP) from 102 +/- 6 to 115 +/- 8 mmHg. An infusion of ACTH (600 micrograms/day) for 7 days, superimposed upon the NE, caused a further rise in AP to a plateau of 143 +/- 9 mmHg after 5 days while cumulative sodium balance fell to -149 +/- 41 meq by the 7th day. Cumulative water balance fell to -660 +/- 232 ml by the 3rd day and then increased slightly. In contrast, when ACTH infusion was repeated during NE infusion while RAP was prevented from increasing using a servo-controlled aortic occluder, cumulative sodium balance increased to 197 +/- 35 meq and AP rose from 108 +/- 5 to 168 +/- 5 mmHg after 7 days and did not plateau. Cumulative water balance rose to 2,325 +/- 445 ml. Thus, in dogs receiving a background infusion of NE, ACTH causes moderate hypertension and natriuresis. However, when RAP is not allowed to rise, ACTH is associated with sodium retention and severe systemic hypertension, suggesting that the natriuretic effects of ACTH are caused by increased RAP and that the natriuresis blunts the chronic hypertensive effects of ACTH.

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The Arteriolar Glycocalyx Plays a Role in the Regulation of Blood Flow in the Iliac of the Anaesthetised Pig

Physiological Research ◽

10.33549/physiolres.933630 ◽

2018 ◽

pp. 41-44 ◽

Cited By ~ 2

Author(s):

T. RUANE-O’HORA ◽

F. MARKOS

Keyword(s):

Blood Flow ◽

Iliac Artery ◽

Flow Measurement ◽

Flow Resistance ◽

Vascular Conductance ◽

Vascular Bed ◽

Resistance Vessels ◽

Flow Pressure

The role of the glycocalyx of arterial resistance vessels in regulating blood flow in vivo is not fully understood. Therefore, the effect of glycocalyx damage using two separate compounds, hyaluronidase and N-Formylmethionyl-leucyl-phenylalanine (fMLP), was evaluated in the iliac artery vascular bed of the anaesthetised pig. Blood flow and pressure were measured in the iliac, an adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3 occlusions at 3-4 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and vascular conductance (flow/pressure) was calculated. Saline, hyaluronidase (14 and 28 µg/ml/min), and fMLP (1 µM/min) were infused separately, downstream of the adjustable snare and their effect on arterial conductance assessed. Hyaluronidase at the higher infusion rate and fMLP both caused a reduction in arterial conductance, and hence an increase in blood flow resistance. In conclusion, the results show that glycocalyx damage causes an increase in resistance to blood flow in the iliac artery vascular bed.

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