scholarly journals Transcriptomic analysis reveals inflammatory and metabolic pathways that are regulated by renal perfusion pressure in the outer medulla of Dahl-S rats

2018 ◽  
Vol 50 (6) ◽  
pp. 440-447 ◽  
Author(s):  
Louise C. Evans ◽  
Alex Dayton ◽  
Chun Yang ◽  
Pengyuan Liu ◽  
Theresa Kurth ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Perfusion Pressure ◽  
Left Kidney ◽  
Respiratory Control ◽  
Renal Perfusion ◽  
Renal Physiology ◽  
Sequencing Analysis ◽  
Functional Changes ◽  
Renal Perfusion Pressure ◽  
Novel Approach

Studies exploring the development of hypertension have traditionally been unable to distinguish which of the observed changes are underlying causes from those that are a consequence of elevated blood pressure. In this study, a custom-designed servo-control system was utilized to precisely control renal perfusion pressure to the left kidney continuously during the development of hypertension in Dahl salt-sensitive rats. In this way, we maintained the left kidney at control blood pressure while the right kidney was exposed to hypertensive pressures. As each kidney was exposed to the same circulating factors, differences between them represent changes induced by pressure alone. RNA sequencing analysis identified 1,613 differently expressed genes affected by renal perfusion pressure. Three pathway analysis methods were applied, one a novel approach incorporating arterial pressure as an input variable allowing a more direct connection between the expression of genes and pressure. The statistical analysis proposed several novel pathways by which pressure affects renal physiology. We confirmed the effects of pressure on p-Jnk regulation, in which the hypertensive medullas show increased p-Jnk/Jnk ratios relative to the left (0.79 ± 0.11 vs. 0.53 ± 0.10, P < 0.01, n = 8). We also confirmed pathway predictions of mitochondrial function, in which the respiratory control ratio of hypertensive vs. control mitochondria are significantly reduced (7.9 ± 1.2 vs. 10.4 ± 1.8, P < 0.01, n = 6) and metabolomic profile, in which 14 metabolites differed significantly between hypertensive and control medullas ( P < 0.05, n = 5). These findings demonstrate that subtle differences in the transcriptome can be used to predict functional changes of the kidney as a consequence of pressure elevation.

Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo

1995 ◽  
Vol 269 (1) ◽  
pp. F134-F139 ◽  
Author(s):  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Perfusion Pressure ◽  
Neuronal Nos ◽  
Oxide Synthase

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma renin activity responses to graded decreases in renal perfusion pressure in fetal and newborn lambs

1992 ◽  
Vol 262 (3) ◽  
pp. R524-R529 ◽  
Author(s):  
N. D. Binder ◽  
D. F. Anderson
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Renin Activity ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
The Right ◽  
The Relationship

We examined the relationship between acute reductions in renal perfusion pressure, as approximated by femoral arterial blood pressure, and plasma renin activity in the uninephrectomized fetal lamb. Renal perfusion pressure was reduced and maintained at a constant value by controlled partial occlusion of the aorta above the renal artery. After 15 min of reduced blood pressure, blood samples were taken for determination of plasma renin activity. This protocol was performed 22 times in 11 fetal lambs. Additionally, three of the fetuses were delivered by cesarean section and studied as newborns for the first week of life. In the fetus, there was a linear relationship between log plasma renin activity and femoral arterial blood pressure (P less than 0.01). After birth, the relationship still existed, although it was shifted to the right (P less than 0.0001). We conclude that there is a significant relationship between plasma renin activity and renal perfusion pressure in the fetal lamb, and as early as 1 day after birth, this relationship shifts to the right in the newborn lamb.

Pressure natriuresis during saline expansion in newborn and adult dogs

1984 ◽  
Vol 246 (6) ◽  
pp. F828-F834 ◽  
Author(s):  
L. I. Kleinman ◽  
R. O. Banks
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
Bilateral Carotid ◽  
Glomerular Filtrate ◽  
Pressure Natriuresis

Pressure natriuresis was studied in anesthetized saline-expanded adult (n = 10) and neonatal (n = 23) dogs. One group (protocol B) received ethacrynic acid and amiloride to block distal nephron function. Studies in the other group (protocol A) were done without diuretics. Renal arterial blood pressure was raised by bilateral carotid artery occlusion. Renal perfusion pressure was then lowered in steps by partially occluding the aorta proximal to the renal arteries. In protocol B carotid occlusion was associated with an increase in both absolute and fractional sodium excretion by adult and newborn dogs. Moreover, there was significant negative correlation (P less than 0.01) between absolute change in renal arterial pressure and change in tubular reabsorption of sodium per milliliter glomerular filtrate for both age groups. For each mmHg increase in blood pressure there was greater inhibition of sodium reabsorption in the puppy (0.55 mueq/ml glomerular filtrate) than in the adult (0.18 mueq/ml, P less than 0.05). In protocol A puppies, the inhibition of sodium reabsorption due to increases in renal perfusion pressure was less than that occurring in protocol B, indicating that some of the sodium escaping proximal nephron reabsorption was reabsorbed distally. Results of these studies indicate that during saline expansion pressure natriuresis is primarily a proximal tubular event, and the sensitivity of the proximal tubule to changes in renal arterial blood pressure is greater in the newborn than the adult kidney.

Snakes and Hypertension

2017 ◽  
Vol 126 (2) ◽  
pp. 321-324
Author(s):  
Edward D. Miller
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Perfusion Pressure ◽  
Renin Angiotensin System ◽  
Renal Perfusion ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renal Perfusion Pressure ◽  
Renal Artery Constriction

Abstract Inhibition of Angiotensin Conversion in Experimental Renovascular Hypertension. By Miller ED Jr, Samuels A, Haber E, and Barger AC. Science 1972; 177:1108–9. Reprinted with permission from AAAS. Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normal in the early phase of renovascular hypertension. These results offer strong evidence that the renin– angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.

Contralateral Natriuresis During Reduced Renal Artery Perfusion Pressure in "Renin-Depleted" Dogs

1972 ◽  
Vol 50 (3) ◽  
pp. 215-227
Author(s):  
L. J. Belleau ◽  
D. Mailhot
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Perfusion Pressure ◽  
Plasma Renin ◽  
Systemic Blood Pressure ◽  
Renal Perfusion ◽  
Systemic Blood ◽  
Renal Perfusion Pressure

The mechanism of contralateral natriuresis subsequent to reduction of renal perfusion pressure was studied. In control dogs a drop in the renal perfusion pressure caused a very significant increase in the arterial and renal venous plasma renin activity, as well as a significant contralateral natriuresis. Systemic blood pressure increased along with contralateral intrarenal resistance. Glomerular filtration rate and renal blood flow did not change in the opposite kidney.In "renin-depleted" dogs a comparable drop in the renal perfusion pressure failed to stimulate renal venous and arterial plasma renin activity. Contralateral natriuresis increased significantly as well as the systemic blood pressure. In the absence of renin, intrarenal resistance of the opposite kidney did not change. Contralateral glomerular filtration rate and renal blood flow remained unchanged.During reduction of renal perfusion pressure, the most significant findings were: (1) absence of renin release despite the stimulation in renin-depleted dogs, (2) increase in contralateral resistance explained by the renin–angiotensin system, (3) systemic blood pressure increment despite renin release inhibition, and (4) the renin–angiotensin system not directly responsible for the contralateral natriuresis following a reduction in the renal perfusion pressure.Contralateral natriuresis cannot be explained by changes in glomerular filtration, renal blood flow, or intrarenal resistance. It is suggested that the rise in blood pressure or another factor, possibly neural or humoral, could explain the contralateral natriuresis.

scholarly journals Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat

1999 ◽  
Vol 276 (3) ◽  
pp. R855-R863 ◽  
Author(s):  
Richard P. E. van Dokkum ◽  
Cheng-Wen Sun ◽  
Abraham P. Provoost ◽  
Howard J. Jacob ◽  
Richard J. Roman
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Renal Damage ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Myogenic Response ◽  
Renal Perfusion Pressure ◽  
Medullary Blood Flow ◽  
Low Blood Pressure

The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contributes to the development of renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney, cortical, and medullary blood flow and PGC were compared in young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume-expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGCwere significantly greater in FHH than in FHL rats. Autoregulation of renal and cortical blood flow was significantly impaired in FHH rats compared with results obtained in FHL rats. Myogenically mediated autoregulation of PGC was significantly greater in FHL than in FHH rats. PGC rose from 46 ± 1 to 71 ± 2 mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg in FHH rats, whereas it only increased from 39 ± 2 to 53 ± 1 mmHg in FHL rats. Isolated perfused renal interlobular arteries from FHL rats constricted by 10% in response to elevations in transmural pressure from 70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats increased by 15%. These results indicate that the myogenic response of small renal arteries is altered in FHH rats, and this contributes to an impaired autoregulation of renal blood flow and elevations in PGC in this strain.

scholarly journals Decreased renal perfusion rapidly increases plasma membrane Na-K-ATPase in rat cortex by an angiotensin II-dependent mechanism

2009 ◽  
Vol 297 (5) ◽  
pp. F1324-F1329 ◽  
Author(s):  
Douglas R. Yingst ◽  
Ali Araghi ◽  
Tabitha M. Doci ◽  
Raymond Mattingly ◽  
William H. Beierwaltes
Keyword(s):  
Blood Pressure ◽  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Cell Surface ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Kidney Cortex ◽  
Renal Perfusion Pressure ◽  
Rapid Changes ◽  
Dependent Mechanism

To understand how rapid changes in blood pressure can regulate Na-K-ATPase in the kidney cortex, we tested the hypothesis that a short-term (5 min) decrease in renal perfusion pressure will increase the amount of Na-K-ATPase in the plasma membranes by an angiotensin II-dependent mechanism. The abdominal aorta of anesthetized Sprague-Dawley rats was constricted with a ligature between the renal arteries, and pressure was monitored on either side during acute constriction. Left renal perfusion pressure was reduced to 70 ± 1 mmHg ( n = 6), whereas right renal perfusion pressure was 112 ± 4 mmHg. In control (nonconstricted) rats ( n = 5), pressure to both kidneys was similar at 119 ± 6 mmHg. After 5 min of reduced perfusion, femoral venous samples were taken for plasma renin activity (PRA) and the kidneys excised. The cortex was dissected, minced, sieved, and biotinylated. Lower perfusion left kidneys showed a 41% increase ( P < 0.003) in the amount of Na-K-ATPase in the plasma membrane compared with right kidneys. In controls, there was no difference in cell surface Na-K-ATPase between left and right kidneys ( P = 0.47 ). PRA was 57% higher in experimental animals compared with controls. To test the role of angiotensin II in mediating the increase in Na-K-ATPase, we repeated the experiments ( n = 6) in rats treated with ramiprilat. When angiotensin-converting enzyme was inhibited, the cell surface Na-K-ATPase of the two kidneys was equal ( P =0.46 ). These results confirm our hypothesis: rapid changes in blood pressure regulate trafficking of Na-K-ATPase in the kidney cortex.

Endothelium-derived relaxing factor regulates renin release in vivo

1992 ◽  
Vol 263 (2) ◽  
pp. F256-F261 ◽  
Author(s):  
D. H. Sigmon ◽  
O. A. Carretero ◽  
W. H. Beierwaltes
Keyword(s):  
Blood Pressure ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Renin Release ◽  
Beta Adrenergic ◽  
Synthesis Inhibition ◽  
Renal Perfusion Pressure ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Endothelium-derived relaxing factor (EDRF), through its inhibitory second messenger guanosine 3',5'-cyclic monophosphate (cGMP), inhibits renin release in vitro. To determine whether EDRF affects renin in vivo, we tested whether EDRF synthesis inhibition could stimulate renin secretion in intact rats. Because EDRF synthesis inhibition increases blood pressure and consequently withdraws sympathetic activity (both renin inhibitory signals), we also studied the effect of L-N omega-nitroarginine methyl ester (L-NAME) when renal perfusion pressure was controlled and during beta-adrenergic blockade. Mean blood pressure (BP), heart rate (HR), and plasma renin activity (PRA) were measured in anesthetized rats before and after EDRF synthesis inhibition by a 10 mg/kg body wt bolus of L-NAME. L-NAME decreased PRA by 67% [from 11.0 +/- 2.7 to 3.7 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, n = 12; P less than 0.001], increased BP by 20 +/- 2 mmHg (P less than 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/min (P less than 0.005). We repeated our experiment in rats instrumented with an intra-aortic balloon catheter to control renal perfusion pressure and pretreated with propranolol to eliminate the beta-adrenergic effect. Under these conditions, L-NAME now increased PRA by 55% (from 6.9 +/- 1.9 to 10.8 +/- 2.6 ng ANG I.ml-1.h-1, n = 12; P less than 0.02), whereas renal perfusion pressure was unchanged (91 +/- 4 vs. 90 +/- 4 mmHg). HR increased slightly from 308 +/- 5 to 315 +/- 3 beats/min (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Renal Perfusion Pressure Determines Infiltration of Leukocytes in the Kidney of Rats With Angiotensin II–Induced Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 849-858 ◽  
Author(s):  
Satoshi Shimada ◽  
Justine M. Abais-Battad ◽  
Ammar J. Alsheikh ◽  
Chun Yang ◽  
Megan Stumpf ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Perfusion Pressure ◽  
Left Kidney ◽  
Renal Perfusion ◽  
Leukocyte Infiltration ◽  
Ang Ii ◽  
Dietary Salt ◽  
Renal Perfusion Pressure ◽  
Induced Hypertension ◽  
The Right

The present study examined the extent to which leukocyte infiltration into the kidneys in Ang II (angiotensin II)-induced hypertension is determined by elevation of renal perfusion pressure (RPP). Male Sprague-Dawley rats were instrumented with carotid and femoral arterial catheters for continuous monitoring of blood pressure and a femoral venous catheter for infusion. An inflatable aortic occluder cuff placed between the renal arteries with computer-driven servo-controller maintained RPP to the left kidney at control levels during 7 days of intravenous Ang II (50 ng/kg per minute) or vehicle (saline) infusion. Rats were fed a 0.4% NaCl diet throughout the study. Ang II–infused rats exhibited nearly a 50 mm Hg increase of RPP (carotid catheter) to the right kidney while RPP to the left kidney (femoral catheter) was controlled at baseline pressure throughout the study. As determined at the end of the studies by flow cytometry, right kidneys exhibited significantly greater numbers of T cells, B cells, and monocytes/macrophages compared with the servo-controlled left kidneys and compared with vehicle treated rats. No difference was found between Ang II servo-controlled left kidneys and vehicle treated kidneys. Immunostaining found that the density of glomeruli, cortical, and outer medullary capillaries were significantly reduced in the right kidney of Ang II–infused rats compared with servo-controlled left kidney. We conclude that in this model of hypertension the elevation of RPP, not Ang II nor dietary salt, leads to leukocyte infiltration in the kidney and to capillary rarefaction.

Abstract P337: Sodium-independent Elevations of Blood Pressure are Accompanied by Immune Cell Infiltration in the Kidney and Renal Damage in Dahl SS Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Brittany M Wade ◽  
David L Mattson
Keyword(s):  
Blood Pressure ◽  
Immune Cells ◽  
Renal Damage ◽  
Immune Cell ◽  
Perfusion Pressure ◽  
Excretion Rate ◽  
Albumin Excretion Rate ◽  
Renal Perfusion ◽  
Immune Cell Infiltration ◽  
Renal Perfusion Pressure

Infiltration of immune cells in the kidney is driven by elevated renal perfusion pressure and amplifies sodium-sensitive hypertension and renal injury in Dahl Salt Sensitive (SS) rats fed a high salt diet. The present studies were performed to determine the importance of immunity in the development of sodium-independent hypertension and renal damage in SS rats and SS lacking T- and B-lymphocytes due to a null mutation in the Rag1 gene (SS-Rag1 em1Mcwi ). The baseline level of mean arterial pressure (MAP) was not different between groups, and the continuous infusion of AngII (5 ng/kg/min, iv) to SS and SS-Rag1 em1Mcwi fed low salt (0.4% NaCl) led to a significantly greater increase in MAP in SS (190±3 mmHg) than in SS-Rag1 em1Mcwi (177±3 mmHg) after 12 days of infusion (n=9 rats/group). Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of AnglI infusion in the SS (from 32±4 to 81±9 mg/day) and in the Rag1 mutants (from 12±2 to 51±8 mg/day). Compared to vehicle-infused rats, kidneys of AngII-treated SS (n=4-5/group) had increased CD45+ total leukocytes (1.8±0.2 vs 4.4±1.2 x 10 6 cells/kidney), including CD11b/c+ macrophages/monocytes and CD3+ T Cells. Upon cessation of the AngII infusion, MAP in the SS-Rag1 em1Mcwi significantly decreased to a level not different from control values (135±5 vs 128±3 mmHg). In contrast, though MAP decreased in the SS when AngII infusion was stopped, blood pressure remained at a level greater than control values throughout the 9-day recovery period (157±8 vs 129±2 mmHg). Albumin excretion rate also tended to decrease in both SS and SS-Rag1 em1Mcwi rats following the return to saline infusion, but the reversibility was not complete. Despite the maintenance of elevated pressure in the SS following AngII withdrawal, there was a significant and complete reversal in the number of CD45+, CD11b/c+, and CD3+ cells in the SS kidneys. The present data indicate that immune cells amplify sodium-independent hypertension and the development of renal damage in the SS rat, but also indicate that factors in addition to renal perfusion pressure may mediate immune cell infiltration into the kidney in hypertension.

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