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.

Central effects of angiotensin II and dopamine in sodium-depleted sheep

1985 ◽  
Vol 248 (5) ◽  
pp. R541-R548
Author(s):  
B. S. Huang ◽  
R. L. Malvin ◽  
R. J. Grekin
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Angiotensin System ◽  
Aldosterone Level ◽  
Central Effects ◽  
Dopaminergic Pathway

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

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.

Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume-expanded rats

1991 ◽  
Vol 260 (6) ◽  
pp. R1200-R1209 ◽  
Author(s):  
D. L. Mattson ◽  
H. Raff ◽  
R. J. Roman
Keyword(s):  
Angiotensin Ii ◽  
Capillary Pressure ◽  
Plasma Levels ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renal Perfusion ◽  
Renal Hemodynamics ◽  
Tubular Reabsorption ◽  
Ang Ii ◽  
The Right

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.

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.

scholarly journals The renin-angiotensin system in the type II diabetic obese Zucker rat.

1993 ◽  
Vol 4 (6) ◽  
pp. 1354-1361
Author(s):  
C T Harker ◽  
M P O'Donnell ◽  
B L Kasiske ◽  
W F Keane ◽  
S A Katz
Keyword(s):  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Type Ii ◽  
Zucker Rat ◽  
Angiotensin System ◽  
Obese Zucker Rat ◽  
Converting Enzyme Inhibition ◽  
Renin Content

Recently, the obese Zucker rat (OZR), an animal model of non-insulin-dependent (type II) diabetes, was shown to respond to converting enzyme inhibition with decreased albuminuria and a marked attenuation of glomerular injury. It was hypothesized that the OZR would possess low plasma renin values and an increased vascular responsiveness to angiotensin II, and therefore, the renin-angiotensin system (PRA, active renin, inactive renin, renal renin content, and plasma angiotensinogen) and vascular reactivity in OZR at 10 and 24 wk of age were investigated. PRA and renin concentration, inactive plasma renin, and renal renin content were all significantly (P < 0.05) reduced in OZR when compared with age-matched lean controls. The ratio of inactive to total renin was significantly increased in the OZR. OZR aortic ring vascular reactivity to KCl, norepinephrine, and angiotensin II was assessed. Despite essentially equal or increased contractile responses to KCl and norepinephrine at both 10 and 24 wk of age, the OZR was not more sensitive to angiotensin II and displayed a significantly reduced contractile response to angiotensin II at 24 wk of age, when compared with lean age-matched controls. It was concluded that the renal protective effect of converting enzyme inhibition in OZR, despite significantly reduced PRA and concentration, inactive plasma renin, and renal renin content, may not be due to a diabetes-induced increased vascular reactivity to angiotensin II.

Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II

1986 ◽  
Vol 251 (1) ◽  
pp. F34-F39 ◽  
Author(s):  
M. S. Paller ◽  
T. H. Hostetter
Keyword(s):  
Angiotensin Ii ◽  
Dietary Protein ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Chronic Administration ◽  
Plasma Renin ◽  
Prostaglandin Synthesis ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Inhibition Of Prostaglandin Synthesis

The effect of dietary protein on the renin-angiotensin system was studied in rats. Rats were fed isocaloric, 50% (high protein, HP), or 6% (low protein, LP) protein diets with identical electrolyte content for 10 days. Food intake and electrolyte excretion were equivalent on the two diets. Plasma renin activity (PRA) was higher in HP (10.0 +/- 2.5 vs. 3.5 +/- 0.5 ng ANG I . ml-1 . h-1, P less than 0.02) as was plasma aldosterone. However, in conscious rats mean arterial pressure (MAP) was not different between groups. The pressor response to graded doses of angiotensin II (ANG II) was diminished by 30-60% with HP (all doses, P less than 0.05). ANG II binding by mesenteric artery smooth muscle particles did not differ between HP and LP. Chronic administration of captopril did not normalize the pressor response in HP. Urinary prostaglandin (PG) E and 6-keto-PGF1 alpha excretion was markedly increased by the HP diet. Acute inhibition of prostaglandin synthesis with meclofenamate restored the pressor response to ANG II in HP to that in LP. In summary, a HP diet increased PRA, plasma aldosterone, urinary PGE, and 6-keto-PGF1 alpha and decreased pressor responsiveness to ANG II. Resistance to ANG II was not reversed by chronic converting enzyme inhibition but was abolished by inhibition of prostaglandin synthesis.

Prostacyclin attenuates both the pressor and adrenocortical response to angiotensin II in human pregnancy

1989 ◽  
Vol 76 (5) ◽  
pp. 529-534 ◽  
Author(s):  
F. Broughton Pipkin ◽  
R. Morrison ◽  
P. M. S. O'Brien
Keyword(s):  
Angiotensin Ii ◽  
Diastolic Pressure ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Normal Pregnancy ◽  
Ang Ii ◽  
Angiotensin System ◽  
Basal Plasma ◽  
Second Trimester Pregnancy

1. The effects of angiotensin II (ANG II) infusion without and with simultaneous infusion of prostacyclin (PGI2; 1.4 pmol min−1 kg−1; 5 ng min−1 kg−1) have been studied in 16 women in second-trimester pregnancy. Ten received one infusion of ANG II alone, followed by its infusion together with PGI2; the remainder received two identical infusions of ANG II alone as controls. 2. PGI2 administration was associated with a small fall in diastolic pressure (P < 0.01) and a proportionally greater rise in heart rate (P < 0.001). Small rises in basal plasma renin and ANG II concentrations and a fall in aldosterone concentration were not statistically significant. 3. The diastolic pressor response to ANG II was blunted during PGI2 infusion by comparison with controls (P < 0.025); this diminution in response was greatest in patients who had initially been most sensitive to ANG II (P < 0.02). 4. The evoked increment in plasma aldosterone during ANG II infusion was considerably reduced (P < 0.005) in the presence of PGI2. 5. These data further support the hypothesis of a role for PGI2 in relation to the blunted pressor response to ANG II of normal pregnancy. The apparent inhibitory effects of PGI2 on aldosterone secretion may partly explain the previously described dissociation between the renin-angiotensin system and aldosterone in pregnancy.

Renal and tubuloglomerular feedback effects of [Sar1,Ala8]angiotensin II in the rat

1982 ◽  
Vol 242 (2) ◽  
pp. F149-F157 ◽  
Author(s):  
D. W. Ploth ◽  
R. N. Roy
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Renin Angiotensin System ◽  
Distal Tubule ◽  
Plasma Renin ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
Renin Angiotensin ◽  
Peritubular Capillaries ◽  
Angiotensin Blockade

Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during control conditions and during renin-angiotensin blockade with the angiotensin II (ANG II) antagonist [Sar1,Ala8]angiotensin II (saralasin, 20 micrograms.kg-1.min-1). Plasma renin activity was increased fourfold during saralasin infusion. Glomerular filtration rate (GFR) and renal blood flow increased in parallel from 1.09 +/- 0.04 to 1.26 +/- 0.05 ml/min and from 6.4 +/- 0.5 to 7.6 +/- 0.5 ml/min, respectively. Absolute and fractional sodium excretion were increased sixfold during ANG II blockade. Hydrostatic pressures in proximal tubules, peritubular capillaries, and distal tubules were unchanged. Estimates of nephron GFR (SNGFR) based on collections of distal tubular fluid were increased from 21.6 +/- 1.2 to 24.3 +/- 0.9 nl/min during ANG II blockade. Increases in SNGFR and decreases in fractional absorption at micropuncture sites beyond the late proximal tubule during saralasin administration resulted in increases of flow rate and Cl- delivery at the early distal tubule. Tubuloglomerular feedback activity, assessed by measuring changes in proximal tubule stop-flow pressure in response to alterations in orthograde microperfusion rate from late proximal tubule sites, was significantly attenuated over the range of physiological flow rates for the late proximal tubule during blockade of the renin-angiotensin system. Acute blockade of ANG II in this rat model results in attenuated tubuloglomerular feedback activity and associated changes of hemodynamic and excretory behavior by the kidney.

Angiotensin II Blockade during Combined Thiazide—β-Adrenoreceptor-Blocker Treatment

1979 ◽  
Vol 57 (s5) ◽  
pp. 123s-125s ◽  
Author(s):  
H. Ibsen ◽  
A. Leth ◽  
A. McNair ◽  
J. Giese
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Diastolic Blood Pressure ◽  
Plasma Volume ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Close Correlation ◽  
Ang Ii ◽  
Arterial Blood ◽  
Change In Mean

1. Sixteen patients (11 male, five female), median age 41 years, with essential hypertension insufficiently controlled by hydrochlorothiazide (75 mg/day; diastolic blood pressure ≥ 100 mmHg), were studied. 2. Plasma renin concentration [renin], plasma angiotensin II concentration ([ANG II]), plasma volume and exchangeable sodium (NaE) were determined, and a saralasin infusion (5·4 nmol min−1 kg−1) was carried out while the patients were on thiazide alone and, in 14 cases, 3 months after addition of a β-adrenoreceptor blocker (propranolol, six, metoprolol, six, and atenolol, two patients). 3. On thiazide alone, saralasin caused a significant decrease in mean arterial blood pressure in 12 out of 16 patients. The saralasin response was closely related to pre-saralasin plasma [ANG II] (r = −0·73, P &lt; 0·01). Plasma [renin] and [ANG II] were higher than normal in the group as a whole. 4. After addition of a β-adrenoreceptor blocker systolic and diastolic blood pressure decreased from 164/109 mmHg to 136/94 mmHg. Plasma [renin] and [ANG II] decreased by 40 and 58% respectively. At this point, saralasin caused no significant change in mean arterial pressure. No close correlation was found between plasma [renin] or [ANG II] or saralasin response on thiazide treatment and changes in blood pressure during subsequent thiazide/β-adrenoreceptor-blocker treatment. Plasma volume and NaE did not change significantly. 5. In patients with thiazide-induced stimulation of the renin—angiotensin system, addition of a β-adrenoreceptor blocker leads to suppression of the system and, at the same time, ANG II-dependence of blood pressure disappears. This contributes to the antihypertensive effect of β-adrenoreceptor blockers in this particular situation.

Humoral responses to intracerebroventricularly administered angiotensin II in dogs

1984 ◽  
Vol 247 (3) ◽  
pp. E336-E342
Author(s):  
T. Eguchi ◽  
E. L. Bravo
Keyword(s):  
Angiotensin Ii ◽  
Plasma Cortisol ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Angiotensin System ◽  
Artificial Cerebrospinal Fluid ◽  
Aldosterone Production ◽  
Humoral Responses

The mechanism(s) by which intracerebroventricularly administered angiotensin II (ANG II) regulates aldosterone production was investigated in dogs with chronically implanted cannula into a lateral cerebroventricle. In salt-replete and salt-depleted dogs, artificial cerebrospinal fluid (CSF) with or without ANG II (1, 10, 100 ng X kg-1 X min-1) was infused intracerebroventricularly for 2 h under pentobarbital anesthesia. Artificial CSF produced no significant humoral changes. Intracerebroventricular ANG II decreased plasma renin activity and increased both ACTH and plasma cortisol in both groups but decreased plasma aldosterone (PA) only in salt-depleted dogs. Dexamethasone pretreatment during intracerebroventricular ANG II decreased PA further in salt-replete but not in salt-depleted dogs. Moreover, the fall in PA during intracerebroventricular ANG II in salt-depleted dogs was prevented when intravenous infusion of ANG II (10 ng X kg-1 X min-1) was given simultaneously to maintain circulating ANG II levels. We conclude that PA response to intracerebroventricular ANG II is mediated primarily through the renin-angiotensin system in the salt-depleted state; however, in the salt-replete state, ACTH assumes a more important role.

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