Abstract MP02: Acute Increases Of Renal Perfusion Pressure Activate Mechanistic Target Of Rapamycin Complex 1 And Increase Macrophage Infiltration In The Kidney Of Sprague Dawley Rats.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Satoshi Shimada ◽  
Chun Yang ◽  
Vikash Kumar ◽  
David L Mattson ◽  
Allen W Cowley
Keyword(s):  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macrophage Infiltration ◽  
Target Of Rapamycin ◽  
Lipocalin 2 ◽  
Sprague Dawley ◽  
Ultrasonic Probe ◽  
Renal Perfusion Pressure ◽  
Mechanistic Target Of Rapamycin ◽  
Pressure Natriuresis

Studies were carried out to determine whether acute elevation of renal perfusion pressure (RPP) activates the mechanistic target of rapamycin complex 1 (mTORC1) and inflammation-related genes which may trigger a rapid infiltration of immune cells. RPP was elevated by 40 mmHg (HP group) for 30 minutes in male SD rats (n=5, 10-12 weeks of age) while measuring renal blood flow (RBF; Transonic ultrasonic probe) and urine flow rate. Sham rats (Sham group) were studied in the same way, but RPP was not changed. Since initial studies found that the acute increase of RPP resulted in activation of mTORC1 (pS6 S235/6 /S6; P<0.05) but not mTORC2 (pAKT T308 /AKT ), the effects of inhibition of mTORC1 with rapamycin (Rapa) pretreatment (1.5 mg/kg; n=10) were then determined (HP+Rapa group). RBF was well autoregulated in both HP and HP+Rapa treated rats averaging 6.9 ± 0.5 vs 7.0 ± 0.8 ml/min/gkw in HP (p=0.72) and 8.1 ± 0.8 vs 8.4 ± 0.5 in HP+Rapa group (p=0.34) with a 40 mmHg elevation of RPP. Pressure-natriuresis was unexpectedly blunted in HP+Rapa treated rats increasing from 0.40 ± 0.21 to 4.0 ± 1.1 in HP rats compared to 0.21 ± 0.07 to 2.3 ± 0.5 μmol/min/gkw; p<0.05) in the HP+Rapa treated rats. Urine volumes were similarly affected. Elevation of RPP increased the mTORC1 activity (pS6 S235/6 /S6) in renal cortex (2.8 ± 0.4 vs 4.8 ± 0.5 A.U.; p<0.05, n=5) and outer medulla (2.0 ± 0.3 vs 5.0 ± 0.6 A.U.; p<0.05, n=5) of HP rats compared to Sham. Rapa treatment suppressed this activation. rtPCR analysis found increased mRNA expression of lipocalin-2 (Lcn2; involved innate immune responses; p<0.05), heme oxygenase (Hmox1; p<0.05) and cyclooxygenase 2 (Cox2; p=0.08) in HP rats compared to Sham, responses which were generally blunted by Rapa. Importantly, as determined by immunohistochemistry, CD68 positive macrophage staining was significantly increased (p<0.001) with elevation of RPP in HP compared to sham rat kidneys. This was significantly reduced by Rapa treatment (p<0.001). We conclude that the mTORC1 pathway can be activated very quickly following elevations of RPP and appears to be responsible for rapid macrophage infiltration which is prevented by Rapa treatment. So too, inhibition of mTORC1 with Rapa reduced the pressure-diuresis response through yet unknown mechanisms.

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.

Renal interstitial hydrostatic pressure and pressure natriuresis in pregnant rats

2000 ◽  
Vol 279 (2) ◽  
pp. F353-F357 ◽  
Author(s):  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium ◽  
Pressure Natriuresis

The objective of this study was to test the hypothesis that a decrease in renal interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9), midterm pregnant (MP; 12–14 days after conception; n = 10), and late-term pregnant (LP; 18–21 days after conception; n = 12) female Sprague-Dawley rats at two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP level, RIHP was 5.9 ± 0.3 mmHg for NP, 3.4 ± 0.4 mmHg for MP ( P < 0.05 vs. NP), and 2.9 ± 0.1 mmHg for LP ( P < 0.05 vs. NP) rats. The increase in RPP from 99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all groups; however, the increases in fractional excretion of sodium (ΔFENa), urine flow rate (ΔV), and ΔRIHP were significantly greater ( P < 0.05) in NP compared with both MP and LP rats. ΔFENa, ΔV, and ΔRIHP were 2.06 ± 0.28%, 81.44 ± 14.10 μl/min, and 3.0 ± 0.5 mmHg for NP; 0.67 ± 0.13%, 28.03 ± 5.28 μl/min, and 0.5 ± 0.2 mmHg for MP; and 0.48 ± 0.12%, 18.14 ± 4.70 μl/min, and 0.4 ± 0.1 mmHg for LP rats. In conclusion, RIHP is significantly lower in pregnant compared with nonpregnant rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP in response to an increase in RPP is blunted. These changes in RIHP may play an important role in the blunted pressure natriuresis and contribute to the conservation of sodium and water that is critical for fetal growth and development during normal pregnancy.

Renal interstitial hydrostatic pressure and PGE2 in pressure natriuresis

1991 ◽  
Vol 260 (5) ◽  
pp. F643-F649 ◽  
Author(s):  
J. M. Gonzalez-Campoy ◽  
C. Long ◽  
D. Roberts ◽  
T. J. Berndt ◽  
J. C. Romero ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Blood Flows ◽  
Renal Perfusion Pressure ◽  
Fractional Excretion Of Sodium ◽  
Anesthetized Dogs ◽  
Pressure Natriuresis ◽  
Indomethacin Treatment

The present study tested the hypothesis that the presence of renal prostaglandin E2 (PGE2) is necessary for full natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during increased renal perfusion pressure (RPP). In control untreated pentobarbital-anesthetized dogs (n = 7), fractional excretion of sodium (FENa) was 1.17 +/- 0.48, 1.07 +/- 0.24, and 2.69 +/- 0.57% at RPP of 90, 122, and 148 mmHg, respectively. These changes in FENa were associated with effective renal blood flows (ERBF) of 1.43 +/- 0.20, 1.49 +/- 0.23, and 1.99 +/- 0.40 ml.min-1.g kidney wt-1, respectively. Similarly, glomerular filtration rate (GFR) was 0.53 +/- 0.10, 0.71 +/- 0.10, and 0.72 +/- 0.14 ml.min-1.g kidney wt-1, respectively. Treatment with indomethacin, a cyclooxygenase inhibitor, significantly lowered FENa to 0.45 +/- 0.13, 0.77 +/- 0.21, and 1.19 +/- 0.59% at RPP of 91, 121, and 146 mmHg, respectively. Additionally, indomethacin treatment lowered ERBF (0.51 +/- 0.15, 0.52 +/- 0.10, and 0.85 +/- 0.21 ml.min-1.g kidney wt-1) and GFR (0.28 +/- 0.09, 0.34 +/- 0.09, and 0.47 +/- 0.09 ml.min-1.g kidney wt-1) at low, middle, and high RPP, respectively. PGE2 replacement (n = 6) into renal artery at 0.01 microgram.min-1.kg body wt-1 returned FENa, ERBF, and GFR to control levels over the same range of RPP, whereas prostacyclin (PGI2) infusion (n = 7) at the same dose did not. RIHP was 4.2 +/- 1.2, 4.2 + 0.5, and 7.5 +/- 1.7 mmHg with increasing RPP in control untreated group and increased to similar levels with indomethacin treatment and during PGE2 or PGI2 replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial appendectomy reduces ANF but not sodium excretion in acute vasopressin hypertension

1990 ◽  
Vol 258 (1) ◽  
pp. R77-R81
Author(s):  
R. S. Zimmerman ◽  
R. W. Barbee ◽  
A. Martinez ◽  
A. A. MacPhee ◽  
N. C. Trippodo
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Circulating Levels

The present study was designed to determine whether atrial appendectomy would decrease the sodium excretion associated with pressor doses of arginine vasopressin (AVP) infusion in rats by decreasing circulating levels of atrial natriuretic factor (ANF). Ten to 21 days after either sham (n = 9) or bilateral atrial appendectomy (n = 13) AVP (19 ng.kg-1.min-1) was infused for 90 min in anesthetized Sprague-Dawley rats. Atrial appendectomy decreased circulating ANF levels from 469 +/- 70 pg/ml in sham-operated animals to 259 +/- 50 pg/ml (P less than 0.05) in atrial-appendectomized animals after 90 min of AVP infusion. Despite a reduction in circulating levels of ANF, sodium excretion, potassium excretion, and urine flow increased and were not affected by bilateral atrial appendectomy. Glomerular filtration rate and mean arterial pressure significantly increased in both groups of rats. The present study supports non-ANF factors such as increases in renal perfusion pressure and/or glomerular filtration rate as potential mechanisms in AVP-induced natriuresis.

beta-Adrenoceptor modulation of renin response to short-term reductions in pressure in young SHR

1992 ◽  
Vol 263 (2) ◽  
pp. R405-R411
Author(s):  
J. P. Porter
Keyword(s):  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Short Term ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Beta Adrenoceptor ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Renal Nerve Activity

The increase in renin secretion in response to short-term (5 min) reductions in arterial pressure has recently been shown to be similar in young spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) animals. This was puzzling, since tonic renal nerve activity is thought to be elevated in the young SHR, and this has the potential to enhance the renin response. The purpose of the present investigation was to determine whether beta-adrenoceptor modulation of pressure-dependent renin release is diminished in the SHR. In conscious, age-matched SHR, WKY, and Sprague-Dawley rats, the effect on arterial plasma renin activity of 5-min reductions in renal perfusion pressure to 90 and 50 mmHg was determined before and during beta-adrenoceptor activation with isoproterenol or beta-adrenoceptor blockade with propranolol. Isoproterenol augmented the renin response at 50 mmHg in all three strains, with the greatest effect occurring in the Sprague-Dawley rats. The response at 90 mmHg was also enhanced in the SHR and Sprague-Dawley rats, but not the WKY rats. Propranolol had no effect in the SHR and WKY animals, but significantly reduced the renin response at 50 mmHg in the Sprague-Dawley rats. Thus, under the conditions of the present investigation (i.e., short-term reductions in pressure), tonic renal nerve activity does not affect pressure-dependent renin release through a beta-adrenergic receptor mechanism in either the SHR or WKY rats. However, under conditions of acute beta-adrenoceptor activation, the renin response is enhanced at a higher renal perfusion pressure in the SHR than in the WKY rat.

Renal autoregulation and pressure natriuresis during ANF-induced diuresis

1987 ◽  
Vol 253 (3) ◽  
pp. F424-F431 ◽  
Author(s):  
R. V. Paul ◽  
K. A. Kirk ◽  
L. G. Navar
Keyword(s):  
Arterial Pressure ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Similar Response ◽  
Water Excretion ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
Pressure Natriuresis ◽  
Atrial Natriuretic

We examined the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) in the anesthetized dog during selective renal arterial infusion of two different synthetic atrial natriuretic factor (ANF) analogues. Rat atriopeptin II (5 X 10(-8) M in renal arterial blood) caused increases in sodium and water excretion but left RBF and GFR unchanged. A similar response was seen with rat 8-33 atrial natriuretic peptide (ANP) (10(-9) M), but a twofold higher dose of this peptide produced a transient increase in RBF and a sustained 16% increase in GFR. The normal pattern of RBF autoregulation in response to decreases in renal perfusion pressure was not altered by either peptide. GFR was also efficiently autoregulated during ANF infusion; however, there was a threefold increase in the slope of the relationship between sodium excretion and arterial pressure (pressure natriuresis) during 8-33 ANP infusion (control 1.11 +/- 0.39, 8-33 ANP 4.00 +/- 0.86 mu eq/mmHg, P less than 0.01). We conclude that ANF-induced diuresis can be sustained without detectable changes in either the autoregulation-responsive or autoregulation-independent components of renal vascular resistance. Factors other than GFR, which are highly responsive to renal perfusion pressure, are important in modulating the natriuresis caused by ANF. The augmentation of pressure natriuresis within the GFR autoregulatory range suggests an influence of ANF on the magnitude of arterial pressure-induced changes in tubular sodium reabsorption.

ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

2004 ◽  
Vol 286 (5) ◽  
pp. R865-R873 ◽  
Author(s):  
Charlotte Mehlin Sorensen ◽  
Paul Peter Leyssac ◽  
Max Salomonsson ◽  
Ole Skott ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Perfusion Pressure ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Perfusion Pressure ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Over Time

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (Pprox), and proximal tubular flow rate (QLP). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl]ED), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 ± 0.3 to 6.0 ± 0.3 ml/min after 5 min (NS) to 5.2 ± 0.2 ml/min after 30 min ( P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 ± 11.0 × 10-5 to 87.1 ± 25.1 × 10-5 Goldblatt units (GU)/ml after 5 min ( P < 0.05) to 158.5 ± 42.9 × 10-5 GU/ml after 30 min ( P < 0.01). GFR, Pprox, and [NaCl]ED all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.

Urinary excretion of urodilatin is increased during pressure natriuresis in the isolated perfused rat kidney

1999 ◽  
Vol 277 (3) ◽  
pp. F347-F351
Author(s):  
Matthias Heringlake ◽  
Klaus Wagner ◽  
Jan Schumacher ◽  
Horst Pagel
Keyword(s):  
Perfusion Pressure ◽  
Rat Kidney ◽  
Renal Perfusion ◽  
Direct Relation ◽  
Renal Perfusion Pressure ◽  
Arterial Blood ◽  
Urinary Potassium ◽  
Perfused Rat Kidney ◽  
Pressure Natriuresis ◽  
Serial Measurements

The findings about mechanisms regulating production and excretion of urodilatin [ANP-(95–126)], a member of the atrial natriuretic peptide (ANP) family, are controversial. To elucidate a possible relationship between arterial blood pressure and renal urodilatin excretion, we studied the effects of different perfusion pressures on urine flow (UV), urinary sodium (UNaV), urinary potassium (UKV), and urodilatin excretion (UUROV), and the concentration of urodilatin in the perfusate (PURO) of isolated perfused rat kidneys. Kidneys were perfused for 180 min with constant perfusion pressures (80 and 120 mmHg, respectively; each, n = 4) in a closed circuit system. Samples of urine and perfusate were taken every 30 min. Mean UV, UNaV, UKV, and UUROV values were significantly higher with a perfusion pressure of 120 mmHg than with 80 mmHg, whereas PURO did not change significantly. Serial measurements revealed no direct relation of UUROV with either UNaV or UV. This suggests that renal perfusion pressure is a determinant of UUROV and that urinary and venous effluent concentrations of urodilatin (probably production) are not coupled directly and that UUROV and UNaV may dissociate during acute variations of sodium excretion and UV.

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