scholarly journals Effects of serelaxin on renal microcirculation in rats under control and high-angiotensin environments

2018 ◽  
Vol 314 (1) ◽  
pp. F70-F80 ◽  
Author(s):  
Weijian Shao ◽  
Carla B. Rosales ◽  
Camila Gonzalez ◽  
Minolfa C. Prieto ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Excretion Rate ◽  
No Synthase ◽  
Urine Flow ◽  
Ang Ii ◽  
Afferent Arterioles

Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation, remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II-infused male rats. Serelaxin increased mean arterial pressure slightly and significantly increased renal blood flow, urine flow, and sodium excretion rate. Group analysis of all serelaxin infusion experiments showed significant increases in GFR. During infusion with subthreshold levels of Ang II, serelaxin did not alter mean arterial pressure, renal blood flow, GFR, urine flow, or sodium excretion rate. Heart rates were elevated during serelaxin infusion alone (37 ± 5%) and in Ang II-infused rats (14 ± 2%). In studies using the in vitro isolated juxtamedullary nephron preparation, superfusion with serelaxin alone (40 ng/ml) significantly dilated afferent arterioles (10.8 ± 1.2 vs. 13.5 ± 1.1 µm) and efferent arterioles (9.9 ± 0.9 vs. 11.9 ± 1.0 µm). During Ang II superfusion, serelaxin did not alter afferent or efferent arteriolar diameters. During NO synthase inhibition (l-NNA), afferent arterioles also did not show any vasodilation during serelaxin infusion. In conclusion, serelaxin increased overall renal blood flow, urine flow, GFR, and sodium excretion and dilated the afferent and efferent arterioles in control conditions, but these effects were attenuated or prevented in the presence of exogenous Ang II and NO synthase inhibitors.

Effects of acute AT1 receptor blockade by candesartan on arterial pressure and renal function in rats

1998 ◽  
Vol 274 (5) ◽  
pp. F940-F945 ◽  
Author(s):  
Ludek Cervenka ◽  
Chi-Tarng Wang ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Urine Flow ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Doppler Flowmetry ◽  
Higher Doses ◽  
Very High

Experiments were performed on normal anesthetized rats to determine the effects of candesartan, a novel AT1 receptor antagonist, on the arterial pressure and renal hemodynamic responses to bolus doses of angiotensin II (ANG II) and on renal hemodynamics and sodium excretion. Control arterial pressure responses to bolus ANG II doses of 10, 50, 100 and 1,000 ng were 26 ± 6, 54 ± 7, 57 ± 7, and 79 ± 7 mmHg; the decreases in cortical renal blood flow (CRBF), measured with laser-Doppler flowmetry, were 47 ± 9, 64 ± 8, 71 ± 6, and 82 ± 6%. The vasoconstrictor responses to ANG II up to 1,000 ng were completely blocked by candesartan doses of 1 and 0.1 mg/kg, whereas treatment with 0.01 mg/kg candesartan attenuated the arterial pressure and CRBF responses. The higher doses of candesartan (1 and 0.1 mg/kg) elicited rapid decreases in arterial pressure, leading to associated decreases in sodium excretion. Renal blood flow (RBF), glomerular filtration rate (GFR), and urine flow also decreased following treatment with candesartan at 1 mg/kg. In contrast, when candesartan was given at 0.01 mg/kg, which did not decrease arterial pressure significantly, there were significant increases in GFR (16 ± 4), RBF (9 ± 2), urine flow (11 ± 2), sodium excretion (35 ± 7), and fractional sodium excretion (39 ± 8%). The inability to overcome blockade, even with very high ANG II doses, indicates that candesartan is a potent noncompetitive blocker of ANG II pressor and renal vasoconstrictor effects. The lower candesartan dose that did not cause significant hypotension elicited substantial increases in RBF, GFR, and sodium excretion, revealing the direct renal vasodilator and natriuretic effects of AT1 receptor blockade.

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

2000 ◽  
Vol 279 (4) ◽  
pp. R1268-R1276 ◽  
Author(s):  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou ◽  
Ole Skøtt
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Sodium Reabsorption ◽  
Osmotic Diuresis ◽  
Nacl Concentration ◽  
Proximal Tubular ◽  
Distal Tubules

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (EDNaCl) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, EDNaCl fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), EDNaClincreased by 3.6 mM, ( P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 μmol NaCl in a smaller volume caused EDNaCl to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron EDNaCl and PRC. We conclude that EDNa decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.

Angiotensin II induces insulin resistance independent of changes in interstitial insulin

1999 ◽  
Vol 277 (5) ◽  
pp. E920-E926 ◽  
Author(s):  
Joyce M. Richey ◽  
Marilyn Ader ◽  
Donna Moore ◽  
Richard N. Bergman
Keyword(s):  
Insulin Resistance ◽  
Heart Rate ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glucose Uptake ◽  
Peripheral Resistance ◽  
Glucose Turnover ◽  
Ang Ii

We set out to examine whether angiotensin-driven hypertension can alter insulin action and whether these changes are reflected as changes in interstitial insulin (the signal to which insulin-sensitive cells respond to increase glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymph) during hyperinsulinemic euglycemic clamps in anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed to alter mean arterial pressure, heart rate, or femoral blood flow. ANG II infusion resulted in increased mean arterial pressure (68 ± 16 to 94 ± 14 mmHg, P < 0.001) with a compensatory decrease in heart rate (110 ± 7 vs. 86 ± 4 mmHg, P < 0.05). Peripheral resistance was significantly increased by ANG II from 0.434 to 0.507 mmHg ⋅ ml−1⋅ min ( P < 0.05). ANG II infusion increased femoral artery blood flow (176 ± 4 to 187 ± 5 ml/min, P < 0.05) and resulted in additional increases in both plasma and lymph insulin (93 ± 20 to 122 ± 13 μU/ml and 30 ± 4 to 45 ± 8 μU/ml, P < 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 ± 1.2 vs. 5.4 ± 0.7 mg ⋅ kg−1⋅ min−1, P > 0.10). Mimicking of the ANG II-induced hyperinsulinemia resulted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in interstitial insulin.

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1988 ◽  
Vol 74 (1) ◽  
pp. 63-69 ◽  
Author(s):  
S. B. Harrap ◽  
A. E. Doyle
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Spontaneously Hypertensive

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from crossbreeding SHR and normotensive Wistar–Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

1987 ◽  
Vol 65 (11) ◽  
pp. 2219-2224 ◽  
Author(s):  
J. Krayacich ◽  
R. L. Kline ◽  
P. F. Mercer
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Fractional Excretion ◽  
Urine Flow ◽  
Fractional Excretion Of Sodium ◽  
Infusion Of Norepinephrine

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.

scholarly journals Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage

2018 ◽  
Vol 315 (2) ◽  
pp. F241-F246
Author(s):  
Sofia Jönsson ◽  
Jacqueline M. Melville ◽  
Mediha Becirovic-Agic ◽  
Michael Hultström
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Oxygen Tension ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Renal Oxygen Consumption ◽  
Significant Difference ◽  
Renal Vascular

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.

Effect of pentobarbital and hemorrhage on renal autoregulation

1985 ◽  
Vol 249 (3) ◽  
pp. F356-F360
Author(s):  
P. C. Kremser ◽  
B. L. Gewertz
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Lower Limit ◽  
Conscious State ◽  
Pressure Flow ◽  
Renal Autoregulation ◽  
Pentobarbital Anesthesia ◽  
Arterial Hemorrhage

Renal blood flow and hemodynamic autoregulation were assessed in seven chronically instrumented canines studied in the conscious state and after pentobarbital anesthesia administration (30 mg/kg). The effects of acute arterial hemorrhage (10 and 15 ml/kg) were also studied. In the conscious state, no significant changes in autoregulation were observed following 10 mg/kg hemorrhage. With pentobarbital and 10 ml/kg hemorrhage, a significant change in the limits of autoregulation was noted (autoregulatory limit 78.5 +/- 16.6 vs. 88.4 +/- 25.3 mmHg, P less than 0.05). Four animals were also studied in the conscious state following 15 ml/kg acute arterial hemorrhage. In these animals, mean arterial pressure decreased (from 105.0 +/- 11.4 to 87.8 +/- 7.2 mmHg, P less than 0.025) but renal blood flow (from 293 +/- 38 to 272 +/- 65 ml/min) and autoregulatory limit did not change. We conclude that renal blood flow is unaffected by hemorrhage or pentobarbital alone. In the conscious state, renal pressure-flow autoregulation is maintained despite moderate hemorrhage and systemic hypotension. The lower limit of autoregulation is significantly changed by even minor hemorrhage in the pentobarbital-anesthetized state.

Effects of the enantiomers of a new dihydropyridine derivative, S12968 and S12967, on renal functions in rats

1993 ◽  
Vol 71 (10-11) ◽  
pp. 848-853
Author(s):  
José M. López-Novoa ◽  
Inmaculada Montañés
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Hypotensive Effect

The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary sodium, potassium, and calcium excretions, mean arterial pressure, and renal vascular resistance were determined before and every 30 min up to 180 min after administration of the tested substance. The levogyre enantiomer S12968, at a dose of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without significant or with minor changes in glomerular filtration rate, renal plasma flow, or renal blood flow. The hypotensive effect was small and nonsignificant. At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal function, induced marked oliguria, and decreased glomerular filtration rate and renal blood flow to almost negligible values. The dextrogyre enantiomer S12967 had much less effect on renal function. These data showing specific stereoselective renal effects are in agreement with pharmacological studies that have demonstrated that S12968 possesses a higher affinity for the dihydropyridine-binding site than its dextrogyre enantiomer, S12967.Key words: Ca channel antagonists, dihydropyridine, glomerular filtration rate, renal blood flow, natriuresis, mean arterial pressure.

Time Course of Systemic and Renal Plasma Prostanoid Concentrations and Renal Function in Ovine Hyperdynamic Sepsis

1994 ◽  
Vol 86 (5) ◽  
pp. 599-610 ◽  
Author(s):  
Andreas Weber ◽  
Ian M. Schwieger ◽  
Olivier Poinsot ◽  
Denis R. Morel
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Creatinine Clearance ◽  
Renal Blood Flow ◽  
Plasma Renin ◽  
Endotoxin Infusion ◽  
Group 2 ◽  
Group 1

1. We continuously recorded systemic and renal haemodynamic changes, and arterial, renal venous and urinary concentrations of thromboxane B2, 6-keto-prostaglandin F1α and prostaglandin E2, and determined their relationship to renal function in an ovine model of progressive hyperdynamic sepsis. 2. Nine chronically instrumented unanaesthetized sheep were given a continuous intravenous infusion of Escherichia coli endotoxin (20 ng min−1 kg−1) for 3 days. 3. Within the first 12 h of infusion, endotoxin induced a major hypotensive septic syndrome, including a persistent 30% reduction in mean arterial pressure, a 50% decrease in systemic vascular resistance and a 50% increase in mean pulmonary artery pressure, associated with severe lactacidaemia. 4. Renal blood flow decreased by 40%, and creatinine clearance, urine flow, and fractional sodium excretion decreased by more than 75%, of baseline values. After 12 h of endotoxin infusion, cardiac output increased two-fold and renal blood flow recovered to baseline values, whereas creatinine clearance remained depressed. Four sheep died between 13 and 22 h of endotoxaemia; these animals (allocated to group 1) presented a significantly and persistently more reduced renal blood flow (−23%) and creatinine clearance (−77%) after 4 h than the remaining five sheep (allocated to group 2), which survived more than 36 h (−16% and −21%, respectively), whereas systemic and pulmonary haemodynamic and gas exchange data remained similar in both groups. 5. The more pronounced decreases in renal blood flow, creatinine clearance and urine flow in group 1 were associated with higher plasma renin activity and plasma 6-keto-prostaglandin F1α concentrations and a lower fractional urinary excretion of 6-keto-prostaglandin F1α than in group 2, whereas plasma thromboxane B2 concentrations were similarly increased in both groups. Plasma prostaglandin E2 concentrations and urinary excretion were not notably affected by endotoxin infusion in either group. 6. Our results are not in favour of a significant renal production of any of these three prostanoids during endotoxaemia. In both groups, values of creatinine clearance were linearly correlated with simultaneous mean arterial pressure values after starting endotoxin infusion (group 1: creatinine clearance = 1.99 × mean arterial pressure −105, r = 0.95; group 2: creatinine clearance = 2.06 × mean arterial pressure −104, r = 0.80). 7. These findings indicate that during continuous endotoxin administration in sheep (1) the renal haemodynamic and functional responses are biphasic, (2) severe impairment of renal function is associated with elevated plasma renin activity and 6-keto-prostaglandin F1α plasma concentrations and with early fatality, and (3) renal filtration capacity directly depends on renal perfusion pressure, suggesting a loss of renal filtration autoregulation during endotoxaemia.

Prostaglandin E2 but not I2 restores furosemide response in indomethacin-treated rats

1986 ◽  
Vol 250 (6) ◽  
pp. F980-F985 ◽  
Author(s):  
K. A. Kirchner ◽  
C. J. Martin ◽  
J. D. Bower
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Prostaglandin E2 ◽  
Renal Blood Flow ◽  
Sodium Excretion ◽  
Prostaglandin Synthesis ◽  
Synthesis Inhibition ◽  
Vasodilatory Effect ◽  
Sodium Load ◽  
Furosemide Administration

Indomethacin attenuates furosemide's natriuretic response. Although this has been attributed to cyclooxygenase inhibition, attempts to correlate prostaglandin (PG) production with furosemide's natriuresis have led some investigators to conclude that prostaglandins are not involved in this response. This study was designed to evaluate the effects of intraaortic administration of PGE2, PGI2 (100 ng X kg-1 X min-1), or the vasodilators secretin or bradykinin (75 microU X kg-1 X min-1) on the furosemide-indomethacin antagonism. Fractional sodium excretion (FENa) during furosemide administration was 4.59 +/- 0.50% in control rats but 1.84 +/- 0.33% in indomethacin-treated rats (Indo) (P less than 0.001). PGE2 prevented indomethacin from attenuating furosemide's response (FENa, 3.91 +/- 0.25%; P = NS vs. control; P less than 0.01 vs. Indo). PGI2, however, failed to prevent the furosemide-indomethacin antagonism (FeNa, 1.94 +/- 0.59%, P less than 0.001 vs. control; P = NS vs. Indo). Inulin clearance, arterial pressure, filtered sodium load, and renal blood flow were not different between groups. Neither secretin nor bradykinin prevented the indomethacin-furosemide antagonism. This study is consistent with the hypothesis that indomethacin antagonizes furosemide's natriuretic response by prostaglandin synthesis inhibition. Furthermore, PGE2 seems to restore furosemide's response through actions other than a vasodilatory effect.

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