Reduced glomerular angiotensin II receptor density in early untreated diabetes mellitus in the rat

1984 ◽  
Vol 247 (1) ◽  
pp. F110-F116 ◽  
Author(s):  
B. J. Ballermann ◽  
K. L. Skorecki ◽  
B. M. Brenner
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Ii ◽  
Salt Intake ◽  
Plasma Renin ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Receptor Density ◽  
Angiotensin Ii Receptor ◽  
Plasma Renin Concentration ◽  
High Salt Intake

Density and affinity of glomerular angiotensin II (ANG II) receptors were determined in normal, untreated, and insulin-treated streptozotocin-diabetic rats 3-4 wk after the onset of diabetes mellitus. With low, intermediate, and high salt intake, angiotensin II receptor density varied inversely with the plasma renin concentration (PRC) in normal, insulin-treated, and untreated diabetic rats. PRC values with all three dietary regimens were lower in the untreated diabetic rats when compared with the other groups. Despite lower plasma renin concentration, however, untreated diabetic rats were also found to have significantly lower glomerular ANG II receptor concentrations at all levels of salt intake. On a normal salt intake, glomerular ANG II receptor density was reduced significantly in untreated diabetic rats (853 +/- 74 (SE) fmol/mg protein), compared with insulin-treated diabetic rats (1,185 +/- 118 fmol/mg) and normal controls (1,058 +/- 83 fmol/mg). ANG II receptor affinity did not change with alternations in salt intake or degree of diabetic control. Reduced glomerular ANG II receptor density in the presence of a suppressed renin-ANG II axis may underlie the altered renal vascular responsiveness to ANG II known to occur in diabetes mellitus.

Hemodynamics, fluid volume, and hormonal responses to chronic high-salt intake in dogs

1990 ◽  
Vol 259 (6) ◽  
pp. H1629-H1636 ◽  
Author(s):  
J. E. Krieger ◽  
J. F. Liard ◽  
A. W. Cowley
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Total Body Weight ◽  
High Salt ◽  
Plasma Sodium ◽  
Plasma Protein Concentration ◽  
Hormonal Responses ◽  
High Salt Intake

The sequential hemodynamics, fluid and electrolyte balances, and the hormonal responses to a 7-day high-salt (NaCl) intake were investigated in sodium-depleted conscious dogs (n = 6). Studies were carried out in metabolic cages mounted on sensitive load cells, which enabled continuous 24 h/day monitoring of total body weight (TBW) as an index of changes in body water. Beat-by-beat hemodynamics were determined 24 h/day. Water (700 ml/day iv) intake was maintained constant. Daily fluid and electrolyte balances and hormonal analyses were performed. An increase of daily salt intake from 8 to 120 meq increased TBW 251 +/- 44 g (P less than 0.05), which was sustained thereafter. Average 24-h mean arterial pressure (MAP) and heart rate (HR) remained unchanged. Average cardiac output (CO) increased 11% (P less than 0.05) above control values by day 2, while total peripheral resistance (TPR) decreased proportionally. CO and TPR returned to control values only when low salt was resumed. Blood volume (BV) was unchanged on day 2 as indicated by direct measurement of BV (51Cr-labeled red blood cells) or by analysis of plasma protein concentration. A 92-meq (P less than 0.05) sodium retention was observed initially, and plasma sodium concentration increased slightly. Plasma renin activity, angiotensin II, and aldosterone levels decreased significantly, whereas vasopressin and atrial natriuretic peptide levels remained unchanged. In summary, chronic high-salt intake resulted in a net retention of water and sodium with no changes in MAP, HR, or BV. The rise in CO was offset by a reduction in TPR, which appeared at least in part related to angiotensin II suppression.

scholarly journals Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats

2017 ◽  
Vol 114 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Jiao Lu ◽  
Hong-Wei Wang ◽  
Monir Ahmad ◽  
Marzieh Keshtkar-Jahromi ◽  
Mordecai P Blaustein ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Cortex ◽  
Salt Intake ◽  
Plasma Corticosterone ◽  
High Salt ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Endogenous Ouabain ◽  
Salt Hypertension

AbstractAimsHigh salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt.Methods and resultsIn protocol I, Wistar rats were infused subcutaneously with low-dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In protocol II, Ang II-high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT1R) blocker (losartan) or vehicles. Ang II alone raised mean arterial pressure (MAP) ∼10 mmHg, but Ang II-high salt increased MAP ∼50 mmHg. Ang II-high salt elevated plasma corticosterone, aldosterone and endogenous ouabain but not Ang II alone. Both Ang II alone and Ang II-high salt increased mRNA and protein expression of CYP11B2 (aldosterone synthase gene) in the adrenal cortex but not of CYP11B1 (11-β-hydroxylase gene). In the aorta, Ang II-high salt increased sodium-calcium exchanger-1 (NCX1) protein. The Ang II-high salt induced increase in MAP was largely prevented by central infusion of MR blockers, benzamil or losartan. Central blockades significantly lowered plasma aldosterone and endogenous ouabain and markedly decreased Ang II-high salt induced CYP11B2 mRNA expression in the adrenal cortex and NCX1 protein in the aorta.ConclusionThese results suggest that in Ang II-high salt hypertension, MR-ENaC-AT1R signalling in the brain increases circulating aldosterone and endogenous ouabain, and arterial NCX1. These factors can amplify blood pressure responses to centrally-induced sympatho-excitation and thereby contribute to severe hypertension.

Enhanced intrarenal receptor-mediated prorenin activation in chronic progressive anti-thymocyte serum nephritis rats on high salt intake

2012 ◽  
Vol 303 (1) ◽  
pp. F130-F138 ◽  
Author(s):  
Yanjie Huang ◽  
Tatsuo Yamamoto ◽  
Taro Misaki ◽  
Hiroyuki Suzuki ◽  
Akashi Togawa ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Salt Intake ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
High Salt ◽  
Ang Ii ◽  
Kidney Fibrosis ◽  
High Salt Intake ◽  
Collecting Ducts

Despite suppression of the circulating renin-angiotensin system (RAS), high salt intake (HSI) aggravates kidney injury in chronic kidney disease. To elucidate the effect of HSI on intrarenal RAS, we investigated the levels of intrarenal prorenin, renin, (pro)renin receptor (PRR), receptor-mediated prorenin activation, and ANG II in chronic anti-thymocyte serum (ATS) nephritic rats on HSI. Kidney fibrosis grew more severe in the nephritic rats on HSI than normal salt intake. Despite suppression of plasma renin and ANG II, marked increases in tubular prorenin and renin proteins without concomitant rises in renin mRNA, non-proteolytically activated prorenin, and ANG II were noted in the nephritic rats on HSI. Redistribution of PRR from the cytoplasm to the apical membrane, along with elevated non-proteolytically activated prorenin and ANG II, was observed in the collecting ducts and connecting tubules in the nephritic rats on HSI. Olmesartan decreased cortical prorenin, non-proteolytically activated prorenin and ANG II, and apical membranous PRR in the collecting ducts and connecting tubules, and attenuated the renal lesions. Cell surface trafficking of PRR was enhanced by ANG II and was suppressed by olmesartan in Madin-Darby canine kidney cells. These data suggest the involvement of the ANG II-dependent increase in apical membrane PRR in the augmentation of intrarenal binding of prorenin and renin, followed by nonproteolytic activation of prorenin, enhancement of renin catalytic activity, ANG II generation, and progression of kidney fibrosis in the nephritic rat kidneys on HSI. The origin of the increased tubular prorenin and renin remains to be clarified. Further studies measuring the urinary prorenin and renin are needed.

Hemodynamics and blood volume in angiotensin II salt-dependent hypertension in dogs

1989 ◽  
Vol 257 (5) ◽  
pp. H1402-H1412 ◽  
Author(s):  
J. E. Krieger ◽  
R. J. Roman ◽  
A. W. Cowley
Keyword(s):  
Cardiac Output ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Salt Intake ◽  
Control Period ◽  
Ang Ii ◽  
Sequential Effects ◽  
High Salt Intake ◽  
Total Body

The sequential effects of an increased daily NaCl intake on hemodynamics, fluid electrolyte balances, and hormonal responses were evaluated in dogs (n = 7) with fixed circulating levels of angiotensin II (ANG II). During the control period, ANG II was infused at 3 ng.kg-1.min-1 while dogs were maintained on an 8 meq NaCl/day diet. Water intake was fixed at 700 ml/day. Continuously recorded (24 h/day) changes of total body weight (TBW) were used as an index of total body water. Cardiac stroke volume and arterial pressure were recorded, and each beat was digitized to provide hourly and 24-h average cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR). After three stable control days, daily salt intake was increased to 120 meq for 7 days. TBW increased gradually to 448 +/- 111 g (2.9%, P less than 0.05) above control by day 3. An 11% expansion of blood volume (P less than 0.05) was found (51CR-labeled red blood cells) on day 2 of high NaCl. CO rose 12% and MAP 20% (P less than 0.05) in parallel with TBW by day 4. By day 7, CO remained only 5% elevated, whereas MAP had stabilized at 20% above control levels. TPR remained significantly elevated from days 3 through 7. A positive Na balance averaging 91 +/- 8 meq (P less than 0.05) occurred on day 1. Plasma Na concentration was increased 2-3 meq/l above control throughout the period of high-salt intake. Plasma renin activity and aldosterone levels decreased to nearly undetectable levels, vasopressin rose slightly, and atrial natriuretic peptide levels increased significantly. Dogs maintained at 8 meq/day NaCl during the same infusion of ANG II showed no changes in MAP, CO, TPR, or TBW. In summary, the salt-induced hypertension was consistently related to small but significant fluid retention, blood volume expansion, elevations of cardiac output, and a gradual increase in TPR.

Changes in angiotensin II receptor density and calcium handling during proliferation in SHR aortic myocytes

1996 ◽  
Vol 271 (6) ◽  
pp. H2330-H2338 ◽  
Author(s):  
S. F. Cortes ◽  
V. S. Lemos ◽  
C. Corriu ◽  
J. C. Stoclet
Keyword(s):  
Angiotensin Ii ◽  
Strain Difference ◽  
Calcium Handling ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Receptor Density ◽  
Angiotensin Ii Receptor ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Wistar Kyoto

The aim of the present work was to characterize angiotensin II (ANG II) receptors and their effect on intracellular free Ca2+ concentration ([Ca2+]i) in proliferating aortic smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Independently from the proliferating state of cultures, apparent affinities of ligands (ANG II > losartan > > CGP-42112A) were consistent with the presence of AT1 receptors in primary cells from SHR and WKY. In proliferating cultures, increases in [Ca2+]i elicited by ANG II (100 nM) were dramatically attenuated or abolished in VSMCs from both strains compared with confluent and postconfluent cultures. Ca2+ releases induced by ionomycin and by ANG II in the absence of extracellular Ca2+ were also impaired in proliferating cultures. In addition, no significant strain difference was found in proliferating cultures with respect to ANG II receptor density, basal [Ca2+]i, and ANG II-induced increases in [Ca2+]i. However, ANG II receptor density significantly increased in SHR, but not in WKY VSMCs at postconfluence. Furthermore, basal [Ca2+]i was elevated in confluent and postconfluent cultures from SHR but not WKY. In confluent cultures, ANG II- and ionomycin-induced Ca2+ releases were enhanced in SHR VSMCs compared with WKY VSMCs. These results show that ANG II-induced Ca2+ release and ionomycin-sensitive Ca2+ stores are enhanced in SHR VSMCs but dramatically decreased in proliferating VSMC cultures from both strains. Mechanisms underlying these alterations remain to be defined. However, the results suggest that alterations in ANG II AT1 receptor density and in intracellular Ca2+ handling in confluent and postconfluent cultures are not associated with the proliferative phenotype of SHR VSMCs. In addition, no evidence for any change in ANG II receptor subtype associated with proliferation of VSMCs was found in either strain.

Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II

1992 ◽  
Vol 263 (5) ◽  
pp. E863-E869 ◽  
Author(s):  
H. Schunkert ◽  
J. R. Ingelfinger ◽  
H. Jacob ◽  
B. Jackson ◽  
B. Bouyounes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Feedback Regulation ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Mrna Levels ◽  
Ang Ii ◽  
Plasma Renin Concentration ◽  
Arterial Blood ◽  
Renin Mrna

The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng.kg-1 x min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg.kg-1 x day-1 quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences.

Salt intake and angiotensin II alter microvessel density in the cremaster muscle of normal rats

1992 ◽  
Vol 263 (3) ◽  
pp. H664-H667 ◽  
Author(s):  
I. Hernandez ◽  
A. W. Cowley ◽  
J. H. Lombard ◽  
A. S. Greene
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Microvessel Density ◽  
Salt Intake ◽  
Plasma Renin ◽  
Ang Ii ◽  
Cremaster Muscle ◽  
Salt Diet ◽  
Dose Dependent Increase ◽  
Dose Dependent

This study investigated the effect of salt intake and angiotensin II (ANG II) levels on microvessel density (MVD). Rats with indwelling arterial and venous catheters were placed on either a high-salt (HS; 4%) or a low-salt diet (LS; 0.4%) for 2 or 4 wk, and blood pressure, heart rate, and plasma renin activity were measured. Plasma ANG II was fixed at normal levels in half of the rats on HS by continuous intravenous infusion of ANG II (5 ng.kg-1.min-1). Samples of cremaster muscle were examined histologically to determine MVD. No difference in MVD was observed between HS and LS groups after 2 wk. After 4 wk on HS, MVD was reduced (22.4%, P less than 0.05) compared with the LS group. In rats fed HS, ANG II infusion induced a significant dose-dependent increase in MVD from 85.11 +/- 3.34 to 98.94 +/- 4.62 (ANG II, 5 ng.kg-1.min-1) and to 107.60 +/- 7.00 (ANG II, 10 ng.kg-1.min-1) (P less than 0.05), with no change in blood pressure. Maintenance of ANG II levels for 4 wk blocked the rarefaction due to salt. These results suggest that the decrease in MVD due to salt could be the result of a dietary-induced fall in plasma ANG II levels.

Angiotensin II receptor alterations during pregnancy in rabbits

1986 ◽  
Vol 251 (1) ◽  
pp. E58-E64 ◽  
Author(s):  
G. P. Brown ◽  
R. C. Venuto
Keyword(s):  
Angiotensin Ii ◽  
Mesenteric Artery ◽  
Dissociation Constants ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Systemic Blood Pressure ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Angiotensin Ii Receptor

Despite activation of the renin-angiotensin system during pregnancy, renal and peripheral vascular blood flows increase, and the systemic blood pressure and the pressor response to exogenous angiotensin II (Ang II) fall. Gestational alterations in Ang II receptors could contribute to these changes. Ang II binding parameters were determined utilizing 125I-Ang II in vascular (glomeruli and mesenteric arteries) and nonvascular (adrenal glomerulosa) tissues from 24- to 28-day pregnant rabbits. Comparisons were made utilizing tissues from nonpregnant rabbits. Binding site concentrations (N) and dissociation constants (Kd) were obtained by Scatchard analyses of binding inhibition data. In glomeruli from nonpregnant and pregnant rabbits, N was 515 +/- 84 and 300 +/- 54 fmol X mg-1 protein (P less than 0.005; n = 8), respectively. Kd did not differ (P greater than 0.05). In mesenteric artery membranes from nonpregnant (n = 3) and pregnant (n = 4) rabbits, N was 304 +/- 21 and 112 +/- 23 fmol X mg-1 (P less than 0.005), respectively. Kd did not differ. Neither N nor Kd differed in adrenal glomerulosa tissues (n = 6). Meclofenamate (M) inhibits prostaglandin synthesis, reduces plasma renin activity, and enhances the pressor response to infused Ang II in pregnant rabbits. Administration of M to pregnant rabbits increased N in glomerular and in mesenteric artery membranes from 298 +/- 16 to 381 +/- 8 fmol X mg-1 (n = 3) and from 144 +/- 13 to 218 +/- 13 fmol X mg-1 (n = 4), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary salt intake modulates progression of antithymocyte serum nephritis through alteration of glomerular angiotensin II receptor expression

2004 ◽  
Vol 286 (2) ◽  
pp. F267-F277 ◽  
Author(s):  
Hiroyuki Suzuki ◽  
Tatsuo Yamamoto ◽  
Naoki Ikegaya ◽  
Akira Hishida
Keyword(s):  
Salt Intake ◽  
Renin Angiotensin System ◽  
Receptor Expression ◽  
Type I ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake ◽  
Glomerular Lesions

Dietary salt intake modulates the renin-angiotensin system (RAS); however, little is known about the effect of salt intake on the progression of glomerulonephritis. We investigated the glomerular expression of TGF-β1 type I (TβRI) and II (TβRII) TGF-β receptors and RAS components in rats with antithymocyte serum (ATS) nephritis on normal (NSI)-, low (LSI)-, and high-salt intake (HSI) and on HSI rats receiving candesartan cilexetil (CC) and LSI rats receiving PD-123319. Glomerular lesions were less severe in rats on LSI and aggravated in those on HSI compared with those on NSI. Intrarenal renin and glomerular ANG II levels were significantly higher in LSI and lower in HSI rats. In ATS nephritis, HSI increased glomerular TβRI, TβRII, and ANG II type 1 receptor (AT1R), and decreased glomerular ANG II type 2 receptor (AT2R), whereas LSI decreased glomerular TGF-β1 and TβRI and increased glomerular AT2R. CC ameliorated glomerular lesions, reduced glomerular TGF-β1 and TβRII, and increased glomerular AT2R. PD-123319 aggravated glomerular lesions and increased glomerular TGF-β1 and TβRII. Our results suggest that dietary salt intake influences progression of ATS nephritis by modulating glomerular TGF-β1 and TβR expression resulting, at least in part, from altered glomerular AT1R and AT2R expression.

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