The PPARγ agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats

2006 ◽  
Vol 291 (6) ◽  
pp. E1228-E1234 ◽  
Author(s):  
Anne Zanchi ◽  
Christine Perregaux ◽  
Marc Maillard ◽  
Daniel Cefai ◽  
Juerg Nussberger ◽  
...  
Keyword(s):  
Sodium Chloride ◽  
Angiotensin Ii ◽  
Zucker Rats ◽  
Ang Ii ◽  
Filtration Fraction ◽  
Intravenous Glucose ◽  
Renal Effects ◽  
Insulin Resistant ◽  
Renal Hemodynamic ◽  
Pparγ Agonist

Glitazones are efficient insulin sensitizers that blunt the effects of angiotensin II (ANG II) in the rat. Sodium chloride is another important modulator of the systemic and renal effects of ANG II. Whether glitazones interfere with the interaction between sodium and the response to ANG II is not known. Therefore, we investigated the effects of pioglitazone on the relationship between sodium and the systemic and renal effects of ANG II in rats. Pioglitazone, or vehicle, was administered for 4 wk to 8-wk-old obese Zucker rats. Animals were fed a normal-sodium (NS) or a high-sodium (HS) diet. Intravenous glucose tolerance tests, systemic and renal hemodynamic responses to ANG II, and the renal ANG II binding and expression of ANG II type 1 (AT1) receptors were measured. The results of our study were that food intake and body weight increased, whereas blood pressure, heart rate, filtration fraction, and insulin levels decreased significantly with pioglitazone in obese rats on both diets. Pioglitazone blunted the systemic response to ANG II and abolished the increased responsiveness to ANG II induced by a HS diet. Pioglitazone modified the renal hemodynamic response to changes in salt intake while maintaining a lower filtration fraction with ANG II perfusion. These effects were associated with a decrease in the number and expression of the AT1 receptor in the kidney. In conclusion, these data demonstrate that the peroxisome proliferator-activated receptor-γ agonist pioglitazone modifies the physiological relationship between sodium chloride and the response to ANG II in insulin-resistant rats.

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2537-H2542 ◽  
Author(s):  
David W. Stepp ◽  
Erika I. Boesen ◽  
Jennifer C. Sullivan ◽  
James D. Mintz ◽  
Clark D. Hair ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zucker Rats ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Insulin Resistant

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

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.

Hypertension in insulin-resistant Zucker obese rats is independent of sympathetic neural support

1992 ◽  
Vol 262 (3) ◽  
pp. E368-E371 ◽  
Author(s):  
M. B. Zemel ◽  
J. D. Peuler ◽  
J. R. Sowers ◽  
L. Simpson
Keyword(s):  
Angiotensin Ii ◽  
Neural Activity ◽  
Vascular Reactivity ◽  
Zucker Rats ◽  
Ganglionic Blockade ◽  
Intravenous Injections ◽  
Insulin Resistant ◽  
Arterial Blood ◽  
Obese Rats ◽  
Blood Pressure Responses

We have previously reported that insulin-resistant Zucker obese rats exhibit hypertension associated with impaired vascular smooth muscle (VSM) Ca2+ transport and proposed that this results from failure of insulin to regulate VSM Ca2+ transport in insulin resistance. However, hypertension in insulin-resistant states is generally attributed to hyperinsulinemia, with a consequent stimulation of sympathetic neural activity. Accordingly, the present study was conducted to determine whether the hypertension observed in Zucker obese rats compared with their lean controls was dependent on either increased sympathetic neural activity or exaggerated vascular reactivity. Intra-arterial blood pressure responses to ganglionic blockade with Ecolid (chlorisondamine chloride) and to graded intravenous injections of angiotensin II and norepinephrine were compared in 6- to 8-wk-old male Zucker rats and their lean controls (n = 10/group). The obese rats exhibited significant hypertension before ganglionic blockade (P less than 0.001), and this difference was largely sustained during ganglionic blockade (P less than 0.005). Furthermore, the obese rats exhibited greater pressor sensitivity to both angiotensin II and to norepinephrine during ganglionic blockade (P less than 0.01). Thus enhanced pressor sensitivity, independent of sympathetic neural activity, appears to support hypertension in Zucker obese rats.

Angiotensin II modulates the intrarenal effects of atrial natriuretic peptide

1988 ◽  
Vol 255 (3) ◽  
pp. F545-F551
Author(s):  
H. M. Siragy ◽  
N. E. Lamb ◽  
C. E. Rose ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Systemic Effects ◽  
Ang Ii ◽  
Renal Effects

The mechanism by which atrial natriuretic peptide (ANP) increases renal water and solute excretion is not fully understood. We studied the renal effects of ANP and angiotensin II (ANG II) separately and together in uninephrectomized conscious dogs (n = 7) in sodium metabolic balance (80 meq/day). Exogenous ANG II and ANP were without measurable systemic effects as demonstrated by absence of changes in blood pressure, plasma aldosterone concentration, and plasma renin activity. The quantity of ANG II that had significant renal effects that were without measurable systemic effects was 0.2 pmol.kg-1.min-1. Three infusion rates of ANP had significant renal effects (1, 10, and 20 pmol.kg-1.min-1). These quantities of ANP caused significant diuresis, natriuresis, kaliuresis, and increased glomerular filtration rate without significant changes in renal plasma flow. ANG II alone caused significant antidiuresis, antinatriuresis, and decreased glomerular filtration rate and renal plasma flow. When ANG II and ANP were given together, no change in urinary flow rate, urinary sodium or potassium excretion, or renal plasma flow was observed, whereas glomerular filtration rate increased. Filtration fraction increased significantly with ANG II and ANP separately and together. Intrarenal ANP prevents the ANG II-induced decrement in urinary sodium excretion and urine flow rate. ANP may play an important role in escape from the sodium-retaining action of intrarenal ANG II.

PIOGLITAZONE BLUNTS THE SYSTEMIC AND RENAL RESPONSE TO ANGIOTENSIN II IN INSULIN RESISTANT OBESE ZUCKER RATS

2004 ◽  
Vol 22 (Suppl. 2) ◽  
pp. S40-S41
Author(s):  
A. Zanchi ◽  
C. Perregaux ◽  
M. R. Maillard ◽  
M. Burnier
Keyword(s):  
Angiotensin Ii ◽  
Zucker Rats ◽  
Renal Response ◽  
Insulin Resistant ◽  
Obese Zucker Rats

Role of angiotensin II in arterial pressure and renal hemodynamics in rats with altered renal development: age- and sex-dependent differences

2013 ◽  
Vol 304 (1) ◽  
pp. F33-F40 ◽  
Author(s):  
Virginia Reverte ◽  
Antonio Tapia ◽  
Goretti Baile ◽  
Juan Gambini ◽  
Ignacio Gíménez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adverse Event ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Mesenteric Arteries ◽  
Renal Development ◽  
Ang Ii ◽  
Renal Hemodynamic ◽  
Age Dependent ◽  
Renal Changes

Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT1 receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT1 receptor antagonist (ARAnp) during the nephrogenic period. ARAnp-treated rats were hypertensive, but an age-dependent rise in AP was only found in males. Three days of treatment with candesartan (7 mg·kg−1·day−1) led to a fall of AP that was greater ( P < 0.05) in male than in female 10- to 11-mo-old ARAnp-treated rats. Oxidated proteins were elevated ( P < 0.05), and the decrease in AP elicited by candesartan was reduced ( P < 0.05) when these rats are also treated with tempol (18 mg·kg−1·day−1). Hypertension was not maintained by an elevation of AT1 receptors in kidneys and mesenteric arteries. The acute renal hemodynamic response to ANG II (30 ng·kg−1·min−1) was similarly enhanced ( P < 0.05) in both sexes of ARAnp-treated rats at 3–4 but not at 10–11 mo of age. Our results suggest that an adverse event during the nephrogenic period induces an ANG II-dependent increment in AP that is aggravated only in males during aging and that oxidative stress but not an increase in AT1 receptor contributes to the rise in AP. This study also shows that the renal hemodynamic sensitivity to ANG II is transitorily enhanced in both sexes of rats with altered renal development.

scholarly journals Angiotensin II and the Renal Hemodynamic Response to an Isolated Increased Renal Venous Pressure in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaohua Huang ◽  
Shereen M. Hamza ◽  
Wenqing Zhuang ◽  
William A. Cupples ◽  
Branko Braam
Keyword(s):  
Angiotensin Ii ◽  
Ace Inhibitor ◽  
Venous Pressure ◽  
Ace Inhibition ◽  
Hemodynamic Response ◽  
Systemic Effect ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Renal Hemodynamic ◽  
Renal Vascular

Elevated central venous pressure increases renal venous pressure (RVP) which can affect kidney function. We previously demonstrated that increased RVP reduces renal blood flow (RBF), glomerular filtration rate (GFR), and renal vascular conductance (RVC). We now investigate whether the RAS and RBF autoregulation are involved in the renal hemodynamic response to increased RVP. Angiotensin II (ANG II) levels were clamped by infusion of ANG II after administration of an angiotensin-converting enzyme (ACE) inhibitor in male Lewis rats. This did not prevent the decrease in ipsilateral RBF (−1.9±0.4ml/min, p&lt;0.05) and GFR (−0.77±0.18ml/min, p&lt;0.05) upon increased RVP; however, it prevented the reduction in RVC entirely. Systemically, the RVP-induced decline in mean arterial pressure (MAP) was more pronounced in ANG II clamped animals vs. controls (−22.4±4.1 vs. −9.9±2.3mmHg, p&lt;0.05), whereas the decrease in heart rate (HR) was less (−5±6bpm vs. −23±4bpm, p&lt;0.05). In animals given vasopressin to maintain a comparable MAP after ACE inhibition (ACEi), increased RVP did not impact MAP and HR. RVC also did not change (0.018±0.008ml/minˑmmHg), and the reduction of GFR was no longer significant (−0.54±0.15ml/min). Furthermore, RBF autoregulation remained intact and was reset to a lower level when RVP was increased. In conclusion, RVP-induced renal vasoconstriction is attenuated when ANG II is clamped or inhibited. The systemic effect of increased RVP, a decrease in HR related to a mild decrease in blood pressure, is attenuated also during ANG II clamp. Last, RBF autoregulation remains intact when RVP is elevated and is reduced to lower levels of RBF. This suggests that in venous congestion, the intact RBF autoregulation could be partially responsible for the vasoconstriction.

Interactions Between Insulin and Angiotensin II on Calcium Mobilization in Skin Fibroblasts from Insulin Resistant Patients with Essential Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 726-726
Author(s):  
Ceolotto Giulio ◽  
Baritono Elisabetta ◽  
Valente Roberto ◽  
Monari Alessandra ◽  
Reato Stefania ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Pertussis Toxin ◽  
Inhibitory Effect ◽  
Skin Fibroblasts ◽  
Ang Ii ◽  
Atpase Inhibitor ◽  
Specific Primers ◽  
Insulin Resistant

P181 Objectives: Insulin attenuates angiotensin II (Ang II)-induced Cai2+ mobilization in insulin sensitive (IS) control subjects. Therefore we compared the interactions between Ang II and insulin on Cai2+ mobilization in skin fibroblasts from insulin resistant (IR) and insulin sensitive (IS) patients with essential hypertension (HT). Methods: Skin fibroblasts from 9 normotensives (NT) and 18 HT were cultured and used after 4 passages. Ca2+ was measured in monolayers of 24h serum-deprived cells using Fura-2 AM. mRNA expression of Gαi2 subunit was determined by RT-PCR using a 5 and 3 specific primers. Results: Resting and Ang II-stimulated (100nM) Cai2+ peak were higher in fibroblasts from HT than NT (76±3 vs 62±3 nM, p<0.01 and 225±8 vs 164±12 nM, p<0.01). In the absence of extracellular Ca2+, the Cai2+ response to Ang II was still significantly enhanced in fibroblasts from HT (212±8 vs 158±9 nM, p<0.01). Thapsigargin (500 nM), a Ca2+ -ATPase inhibitor, induced a Cai2+ rise that was similar in HT and NT (from 42±7 to 93±15 vs 52±5 to 106±8 nM). Pertussis toxin (20ng/ml, 6h), inhibitor of Gαi2 subunit, reduced Ang II stimulated Cai2+ peak both in NT (from 153±7 to 98±8nM, p<0.01) and HT (from 189±16 to 138±12, p<0.01). In IS HT, insulin (100 nM, 20 min) blunted the Ang II stimulated Cai2+ response (from 208±9 to 167±9 nM, p<0.01), while in IR HT it did not (from 205±16 to 208±13 nM, ns). Pertussis toxin attenuated AngII stimulated Cai2+ peak in IS HT (from 208±4 to 112±2 p<0.01), but not in IR HT (from 207±10 to 165±9). mRNA expression of Gαi2 subunit was increased in IR HT compared to IS HT. Conclusion: In human skin fibroblasts the inhibitory effect of insulin on Ang II - induced Cai2+ mobilization is blunted in IR HT by a pertussis toxin sensitive mechanism, probably involving a Gαi2subunit.

Renal response to atrial natriuretic factor is modulated by intrarenal angiotensin II

1988 ◽  
Vol 254 (3) ◽  
pp. R453-R456 ◽  
Author(s):  
C. J. Showalter ◽  
R. S. Zimmerman ◽  
T. R. Schwab ◽  
B. S. Edwards ◽  
T. J. Opgenorth ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Filtration Rate ◽  
Ang Ii ◽  
Natriuretic Factor ◽  
Renal Hemodynamic ◽  
Atrial Natriuretic

The present study in anesthetized dogs (n = 8) was designed to test the hypothesis that intrarenal angiotensin II (ANG II) attenuates the increase in sodium excretion in response to atrial natriuretic factor (ANF). To test this hypothesis, renal hemodynamic and excretory responses to systemically administered ANF (0.3 micrograms.kg-1.min-1) were assessed in the presence of ANG II infusion into the left kidney (ANG II K) at a nonpressor dose (1.5 ng.kg-1.min-1) and with an infusion of saline into the right kidney, the latter which served as control (CK). During ANF infusion, absolute increases in urinary sodium excretion (delta + 160.8 +/- 44.7 vs. delta + 369.4 +/- 56.9 mu eq/min, P less than 0.005) and fractional sodium excretion (delta + 2.55 +/- 0.62 vs. delta + 4.26 +/- 0.82%, P less than 0.03) were markedly attenuated in the ANG II K compared with CK. Glomerular filtration rate increased only in the CK. Urine osmolality decreased in both the ANG II K and CK. These studies demonstrate an attenuated natriuresis to ANF in the presence of intrarenally infused ANG II, which is associated with a blunted increase in glomerular filtration rate. These studies support the hypothesis that the renal hemodynamic and excretory responses to ANF are modulated by intrarenal ANG II.

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