Comparative sensitivities of isolated rat renal arterioles to endothelin

1992 ◽  
Vol 263 (5) ◽  
pp. F894-F899 ◽  
Author(s):  
D. M. Lanese ◽  
B. H. Yuan ◽  
I. F. McMurtry ◽  
J. D. Conger
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Competitive Inhibitor ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Vasoconstrictor Response ◽  
Series Of Experiments ◽  
Respective Concentration

The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P , 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P , 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P , 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(–7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity.

Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide

2007 ◽  
Vol 292 (1) ◽  
pp. H83-H92 ◽  
Author(s):  
Armin Just ◽  
Andrea J. M. Olson ◽  
Christina L. Whitten ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Oxygen Species ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Adrenergic Agonist ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats

NAD(P)H oxidases (NOX) and reactive oxygen species (ROS) are involved in vasoconstriction and vascular remodeling during hypertension produced by chronic angiotensin II (ANG II) infusion. These effects are thought to be mediated largely through superoxide anion (O2−) scavenging of nitric oxide (NO). Little is known about the role of ROS in acute vasoconstrictor responses to agonists. We investigated renal blood flow (RBF) reactivity to ANG II (4 ng), norepinephrine (NE, 20 ng), and α1-adrenergic agonist phenylephrine (PE, 200 ng) injected into the renal artery (ira) of anesthetized Sprague-Dawley rats. The NOX inhibitor apocynin (1–4 mg·kg−1·min−1 ira, 2 min) or the superoxide dismutase mimetic Tempol (1.5–5 mg·kg−1·min−1 ira, 2 min) rapidly increased resting RBF by 8 ± 1% ( P < 0.001) or 3 ± 1% ( P < 0.05), respectively. During NO synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester, 25 mg/kg iv), the vasodilation tended to increase (apocynin 13 ± 4%, Tempol 10 ± 1%). During control conditions, both ANG II and NE reduced RBF by 24 ± 4%. Apocynin dose dependently reduced the constriction by up to 44% ( P < 0.05). Similarly, Tempol blocked the acute actions of ANG II and NE by up to 48–49% ( P < 0.05). In other animals, apocynin (4 mg·kg−1·min−1 ira) attenuated vasoconstriction to ANG II, NE, and PE by 46–62% ( P < 0.01). During NOS inhibition, apocynin reduced the reactivity to ANG II and NE by 60–72% ( P < 0.01), and Tempol reduced it by 58–66% ( P < 0.001). We conclude that NOX-derived ROS substantially contribute to basal RBF as well as to signaling of acute renal vasoconstrictor responses to ANG II, NE, and PE in normal rats. These effects are due to O2− rather than H2O2, occur rapidly, and are independent of scavenging of NO.

A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli

2005 ◽  
Vol 288 (6) ◽  
pp. F1183-F1190 ◽  
Author(s):  
Rekha Singh ◽  
Ashok K. Singh ◽  
David J. Leehey
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Ang Ii ◽  
Sprague Dawley ◽  
New Information ◽  
Sprague Dawley Rats ◽  
And Control

Recent evidence suggests that the intrarenal renin-angiotensin system (RAS) may play an important role in the development of glomerular changes associated with diabetic nephropathy. In this study, the glomerular RAS was examined in male Sprague-Dawley rats made diabetic with streptozotocin (STZ), and the findings compared with those obtained in control nondiabetic rats. In diabetic rat glomerular extracts, angiotensinogen and angiotensin II (ANG II) levels were increased significantly by 2.2- and 1.9-fold, respectively, compared with nondiabetic controls. No significant differences in ANG I and angiotensin-converting enzyme (ACE) levels were observed between these groups. The HPLC analysis of the glomerular extracts demonstrated that exogenous ANG I was converted into various ANG peptides including ANG II, ANG(1–9), and ANG(1–7). A significant increase in formation of ANG II from exogenous ANG I was observed in STZ rats compared with control rats. Preincubation of glomerular extracts with captopril resulted in a 20–30% decrease in ANG II conversion from exogenous ANG I in diabetic and control rats. The possible role of ANG(1–9) in formation of ANG II was examined by HPLC. Exogenous ANG(1–9) in glomerular extracts was converted into ANG II, this conversion being significantly higher in STZ rats than in control rats. These findings provide new information that ANG(1–9) is produced in rat glomerular extracts, can be converted to ANG II, and that this conversion is also stimulated in diabetic rat glomeruli. Thus this study demonstrates that in diabetic rats, glomerular ANG II levels are increased due to an increase in angiotensinogen and an increase in the formation of ANG II.

scholarly journals Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin

2011 ◽  
Vol 12 (4) ◽  
pp. 404-412 ◽  
Author(s):  
Maydelin Muñoz ◽  
Jaimar Rincón ◽  
Adriana Pedreañez ◽  
Ninoska Viera ◽  
Juan P Hernández-Fonseca ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Macrophage Infiltration ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group Water ◽  
Proinflammatory Role ◽  
Renal Expression ◽  
Losartan Treatment

Introduction: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT1 receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. Materials and methods: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O2-) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. Results: ADR rats showed increased expression of ICAM-1, Ang II, O2- and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. Conclusions: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT1 receptors.

scholarly journals Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

2010 ◽  
Vol 298 (1) ◽  
pp. F177-F186 ◽  
Author(s):  
Anne D. M. Riquier-Brison ◽  
Patrick K. K. Leong ◽  
Kaarina Pihakaski-Maunsbach ◽  
Alicia A. McDonough
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Volume Flow Rate ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Associated Proteins ◽  
Gradient Fractionation

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na+/H+ exchanger isoform 3 (NHE3), Na+/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 μg/min for 20 min) that increased PT flow rate ∼20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng·kg−1·min−1 for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H+-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

Renal hemodynamic responses to increased renal venous pressure: role of angiotensin II

1982 ◽  
Vol 243 (3) ◽  
pp. F260-F264 ◽  
Author(s):  
P. R. Kastner ◽  
J. E. Hall ◽  
A. C. Guyton
Keyword(s):  
Angiotensin Ii ◽  
Filtration Rate ◽  
Enzyme Inhibitor ◽  
Venous Pressure ◽  
Renin Secretion ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Filtration Fraction ◽  
A Value

Studies were performed to quantitate the effects of progressive increases in renal venous pressure (RVP) on renin secretion (RS) and renal hemodynamics. RVP was raised in 10 mmHg increments to 50 mmHg. Renin secretion rate increased modestly as RVP was increased to 30 mmHg and then increased sharply after RVP exceeded 30 mmHg. Glomerular filtration rate (GFR), renal blood flow (RBF), and filtration fraction (FF) did not change significantly when RVP was elevated to 50 mmHg. GFR and RBF were also measured after the renin-angiotension system (RAS) was blocked with the angiotensin converting enzyme inhibitor (CEI) SQ 14225. After a 60-min CEI infusion, RBF was elevated (32%), GFR was unchanged, FF was decreased, and total renal resistance (TRR) was decreased. As RVP was increased to 50 mmHg, GFR and FF decreased to 36.3 and 40.0% of control, respectively, RBF returned to a value not significantly different from control, and TRR decreased to 44.8% of control. The data indicate that the RAS plays an important role in preventing reductions in GFR during increased RVP because blockade of angiotensin II (ANG II) formation by the CEI results in marked decreases in GFR at high RVPs. The decreases in GFR after ANG II blockade and RVP elevation were not due to lack of renal vasodilation, since TRR was maintained below while RBF was maintained either above or at the pre-CEI levels.

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

1985 ◽  
Vol 248 (3) ◽  
pp. R371-R377 ◽  
Author(s):  
B. S. Huang ◽  
M. J. Kluger ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Body Temperature ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Significant Rise ◽  
Ang Ii ◽  
Deep Body Temperature ◽  
Angiotensin System ◽  
Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Abstract 41: Fructose Stimulates Na/H Exchanger 3 Activity and Enhances the Ability of Angiotensin II to Activate Na/H Exchanger 3 in the Proximal Tubule

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pablo Cabral ◽  
Nancy Hong ◽  
Jeffrey Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Physiological Saline ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Basal Rate ◽  
Low Concentrations ◽  
Sprague Dawley Rats ◽  
High Fructose ◽  
Salt Sensitive Hypertension

Consumption of high-fructose corn syrup as a sweetener has increased dramatically. Fructose has been implicated in the epidemic of diabetes, obesity and hypertension including salt-sensitive hypertension. However, the mechanisms are poorly understood. The proximal nephron reabsorbs 60-70% of the fluid and Na, and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport has been implicated in several forms of hypertension. We hypothesized that fructose stimulates NHE3 activity and enhances the ability of angiotensin II (ANG II) to activate NHE3 in the proximal tubule. To test our hypothesis we isolated and perfused proximal tubules from Sprague Dawley rats. NHE3 activity was measured as the recovery of intracellular pH after an NH4Cl acid pulse using the pH sensitive dye BCECF. The rate of pH recovery was measured in Fluorescent Units per second (FU/sec). In the presence of a 5.5 mM glucose-containing physiological saline the basal rate of pH recovery was 3.1 ± 0.8 FU/sec. When the luminal solution was exchanged to a 0.6 mM glucose + 5 mM fructose-containing physiological saline in a second period, the rate of pH recovery increased to 5 ± 1 FU/sec (p<0.03, n=8).To study whether this effect was due to the addition of fructose or the removal of glucose to the lumen, we performed a separate set of experiments where 5 mM glucose was substituted for 5 mM fructose. In the presence of 0.6 mM glucose the basal rate of pH recovery was 3.6 ± 1.5 FU/sec. When 5 mM fructose was added the rate of pH recovery increased to 5.9 ± 2 FU/sec (p<0.02, n=5). Control experiments showed no differences between periods when 5 mm glucose was added back to the luminal perfusate. Finally, we tested the effect of low concentrations of ANG II in the presence or absence of luminal fructose. In the presence of 5.5 mM glucose, ANG II 10-12 M did not affect the rate of pH recovery (change: -1.1 ± 0.5 FU/sec, n=9). However, in the presence of 5 mM fructose, ANG II increased the rate of pH recovery (change: 4.0 ± 2.2 FU/sec, p< 0.03 n=6). We conclude that acute treatment with fructose stimulates NHE3 activity and enhances the ability of ANG II to activate NHE3 in the proximal tubule. These results may partially explain the mechanism by which a fructose diet induces hypertension.

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II

1993 ◽  
Vol 265 (3) ◽  
pp. R591-R595 ◽  
Author(s):  
R. L. Thunhorst ◽  
S. J. Lewis ◽  
A. K. Johnson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Arterial Blood ◽  
Endogenous Formation

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

scholarly journals Contrasting pharmacological ETB receptor blockade with genetic ETB deficiency in renal responses to big ET-1

2001 ◽  
Vol 6 (1) ◽  
pp. 39-43 ◽  
Author(s):  
DAVID M. POLLOCK
Keyword(s):  
Renal Plasma Flow ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Clearance Studies ◽  
Etb Receptor ◽  
Pharmacological Blockade ◽  
Series Of Experiments ◽  
Renal Responses

Renal clearance studies were conducted to determine the role of ETB receptors in the renal response to big endothelin-1 (big ET-1). Two series of experiments were conducted on Inactin-anesthetized rats to contrast acute pharmacological blockade of ETB receptors vs. genetic ETB receptor deficiency. In the first series, Sprague-Dawley rats were given either ETB-selective antagonist, A-192621, or vehicle (0.9% NaCl) prior to infusion of big ET-1 (10 pmol·kg−1·min−1) for 60 min. A-192621 significantly increased baseline mean arterial pressure (MAP; 102 ± 4 vs. 141 ± 6 mmHg, P < 0.05) and urine flow rate (0.5 ± 0.1 vs. 1.3 ± 0.2 μl/min, P < 0.05) without any effect on glomerular filtration rate (GFR) or effective renal plasma flow (ERPF). Big ET-1 significantly increased MAP in both groups but to a higher level in rats given antagonist (120 ± 6 vs. 169 ± 6 mmHg, P < 0.05). Big ET-1 increased urine flow in control rats but decreased in rats given antagonist. GFR and ERPF were decreased in rats given big ET-1, an effect that was exaggerated by ETB blockade. Another series of experiments examined the response to big ET-1 in rats lacking functional renal ETB receptors, known as spotting lethal ( sl) rats. Surprisingly, rats heterozygous ( sl/+) for ETB receptor deficiency had a significantly higher baseline MAP compared with homozygous ( sl/ sl) rats (134 ± 6 vs. 112 ± 7 mmHg, P < 0.05), although other variables were similar. Big ET-1 produced no significant change in MAP in either group. Urine flow, GFR, and ERPF were significantly decreased in both groups, although these changes were much larger in sl/ sl rats. These experiments indicate that the ETB receptor plays an important role in limiting the renal hemodynamic response to big ET-1. Furthermore, the diuretic actions of big ET-1 require a functional ETB receptor.

Mechanism of the biphasic arteriolar response to angiotensin II

1984 ◽  
Vol 247 (1) ◽  
pp. H88-H94 ◽  
Author(s):  
J. T. Fleming ◽  
I. G. Joshua
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin Synthesis ◽  
Krebs Solution ◽  
Ang Ii ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
Third Order ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Alpha Chloralose

Male Sprague-Dawley rats (140-180 g) were anesthetized with alpha-chloralose and urethan. The cremaster muscle with intact blood supply and neural innervation was suspended in a tissue bath containing a modified Krebs solution. With the use of television microscopy the luminal diameters of third-order arterioles (14-32 micron) were measured before and after adding angiotensin II (ANG II, bath concn 10(-6) M). The arterioles responded to ANG II with an initial, transient constriction followed by a more prolonged dilation to a diameter larger than the control diameter. Pretreating the muscle with [Sar1, Ile8]ANG II significantly attenuated both the arteriolar constriction and subsequent dilation induced by ANG II. Treatment of the cremaster muscle with mefenamic acid or indomethacin, inhibitors of prostaglandin synthesis, produced a significant reduction in the diameter of the arterioles and abolished the dilator phase of the arteriolar response to ANG II without preventing the ANG II-induced constriction. These results demonstrate that within the intact microcirculation, ANG II produces both an arteriolar constriction and a dilation that are mediated by specific ANG II receptors. The ANG II-induced dilation of the arterioles appears to be caused by increased prostaglandin synthesis and release.

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