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.

Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development

1994 ◽  
Vol 266 (6) ◽  
pp. F911-F918 ◽  
Author(s):  
A. Tufro-McReddie ◽  
D. W. Johns ◽  
K. M. Geary ◽  
H. Dagli ◽  
A. D. Everett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Angiotensin Ii ◽  
Mrna Levels ◽  
Ang Ii ◽  
Kidney Weight ◽  
Renal Growth ◽  
Renin Mrna

To determine whether angiotensin II (ANG II) modulates renal growth and renin and angiotensin type 1 (AT1) gene expression via AT1 during development, weanling rats were given ANG II antagonist losartan (DuP 753) for 3 wk. Body weight (g), kidney weight (g), and kidney weight-to-body weight ratio were lower in losartan-treated rats (162 +/- 7, 1.6 +/- 0.06, and 9.5 +/- 0.1 x 10(-3)) than in control rats (184 +/- 5, 1.8 +/- 0.07, and 10.1 +/- 0.1 x 10(-3); P < 0.05). Renal DNA content (mg/kidney) was lower in losartan-treated (2.4 +/- 0.17) than in control rats (3.3 +/- 0.31; P < 0.05), whereas protein-to-DNA and RNA-to-DNA ratios were similar in losartan-treated and control rats. Renin mRNA levels were sevenfold higher in losartan-treated than in control rats, as determined by quantitative standardized dot blot analysis. In addition, blockade of AT1 with losartan induced recruitment of renin-synthesizing and renin-containing cells in the renal vasculature, as determined by immunocytochemistry and in situ hybridization. To establish whether AT1 blockade has a direct effect on renin gene expression, freshly isolated renin-producing cells were exposed in vitro to losartan (10(-6) M) or culture media (control). Losartan induced a twofold increase in steady-state renin mRNA levels above control (P < 0.05). Intrarenal AT1 mRNA levels were not altered by losartan given either in vivo or in vitro to freshly dispersed cells. To define whether immature renin-secreting cells are responsive to ANG II, renin release was determined by reverse hemolytic plaque assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy

1993 ◽  
Vol 264 (5) ◽  
pp. F874-F881 ◽  
Author(s):  
S. S. el-Dahr ◽  
J. Gee ◽  
S. Dipp ◽  
B. G. Hanss ◽  
R. C. Vari ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Obstructive Nephropathy ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Kininase Ii ◽  
Plasma Angiotensin ◽  
Renin Mrna

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.

scholarly journals Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension

2014 ◽  
Vol 307 (8) ◽  
pp. F931-F938 ◽  
Author(s):  
Nirupama Ramkumar ◽  
Deborah Stuart ◽  
Sara Rees ◽  
Alfred Van Hoek ◽  
Curt D. Sigmund ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Plasma Renin ◽  
Ang Ii ◽  
Water Excretion ◽  
Protein Levels ◽  
Renin Gene ◽  
Induced Hypertension ◽  
Renin Mrna ◽  
Exon 1

The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng·kg−1·min−1 resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 ± 4 mmHg in KO vs. 128 ± 3 mmHg in controls). Urinary renin excretion and epithelial Na+ channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression.

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life

1992 ◽  
Vol 262 (3) ◽  
pp. R459-R463 ◽  
Author(s):  
W. V. Page ◽  
S. Perlman ◽  
F. G. Smith ◽  
J. L. Segar ◽  
J. E. Robillard
Keyword(s):  
Gene Expression ◽  
Plasma Renin ◽  
Renal Nerves ◽  
Mrna Levels ◽  
Angiotensin I ◽  
Fetal Sheep ◽  
Close Analysis ◽  
Renin Gene ◽  
Renin Mrna

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Angiotensin causes vasoconstriction during hemorrhage in baroreceptor-denervated dogs

1983 ◽  
Vol 245 (4) ◽  
pp. H667-H673
Author(s):  
D. B. Averill ◽  
A. M. Scher ◽  
E. O. Feigl
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Aortic Pressure ◽  
Ang Ii ◽  
Arterial Blood ◽  
Aortic Blood ◽  
Aortic Blood Pressure ◽  
Mean Aortic Pressure

The participation of angiotensin II (ANG II) in the maintenance of arterial blood pressure during hypotensive hemorrhage was examined in unanesthetized, baroreceptor-denervated dogs. When mean aortic blood pressure was reduced to 69.0 +/- 2.2 mmHg, plasma renin activity increased from 0.6 +/- 0.3 ng ANG I X ml-1 X h-1 during the prehemorrhage control period to 4.5 +/- 1.6. Twenty minutes after the hemorrhage, mean aortic blood pressure rose to 78.9 +/- 3.1 mmHg. Subsequent infusion of the angiotensin II antagonist saralasin (5.2-14.0 micrograms X kg-1 X min-1) decreased mean aortic pressure to 59.6 +/- 3.3 mmHg. When 5% dextrose was infused in place of saralasin, mean aortic pressure was 79.3 +/- 4.3 mmHg. The lower aortic blood pressure caused by saralasin infusion was the result of a significant decrease in total peripheral resistance. Resistance was 10.3 +/- 3.2 mmHg X l-1 X min lower during saralasin infusion than during dextrose infusion. We conclude that baroreceptor reflexes are not essential for the elevation of plasma renin activity during hemorrhage. In baroreceptor-denervated dogs subjected to hypotensive hemorrhage, the increased formation of ANG II has a vasoconstrictor action that contributes to the maintenance of arterial blood pressure.

Angiotensin II and the maturation of renal cortical Na+/H+ exchanger activity during fetal life in sheep

1996 ◽  
Vol 271 (6) ◽  
pp. R1507-R1513 ◽  
Author(s):  
E. N. Guillery ◽  
M. S. Mathews ◽  
J. Orlowski ◽  
J. E. Robillard
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Membrane Vesicles ◽  
Plasma Renin ◽  
Fetal Life ◽  
Maximal Velocity ◽  
Mrna Levels ◽  
Ang Ii ◽  
The Difference ◽  
Near Term

The postnatal rise in renal Na+ reabsorption is associated with an increase in proximal tubule apical membrane Na+/H+ exchanger (NHE) activity in sheep. Inasmuch as circulating angiotensin II (ANG II) levels increase immediately after birth and ANG II is known to upregulate NHE activity in the adult proximal tubule, we postulated that ANG II plays a role in mediating maturational changes in NHE activity. We therefore studied the effects of ANG II infusion (10 micrograms/h) for 24 h on renal cortical NHE activity in chronically instrumented, twin ovine fetuses (129 +/- 2 days gestation, term is 145 days, n = 10 pairs); one twin of each pair served as a control. After 24 h, the fetuses were killed and brush-border membrane vesicles (BBMV) were prepared from the renal cortices. Postinfusion plasma ANG II levels were significantly higher and plasma renin activities were significantly lower in treated fetuses compared with controls. Kinetic analysis revealed an increase in NHE activity after ANG II treatment; however, the difference was not statistically significant: maximal velocity (in nmol.s-1.mg protein-1) control 1.65 +/- 0.50, treated 2.31 +/- 0.66 (P = 0.11, n = 9 pairs); Michaelis constant control 8.29 +/- 1.17 mM, treated 9.84 +/- 1.26 mM (P = 0.11). Northern blots of total RNA from the cortices of these animals were hybridized to a D-[32P]UTP-labeled antisense RNA probe prepared from a 1.3-kb rat NHE3 cDNA fragment. There were no differences between the groups in NHE3 mRNA levels (32P counts were control 413 +/- 54, treated 340 +/- 46). ANG II does not appear to play an important role in the regulation of NHE activity in the proximal tubule of the near-term sheep fetus.

scholarly journals Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2012 ◽  
Vol 215 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Juan M Saavedra ◽  
Ashok Kumar ◽  
Varunkumar Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna ◽  
Receptor Gene Expression

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2 receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2 receptor mRNA levels, but the decline was more transient. AT1A receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1 receptor antagonist) or with CGP42112 (AT2 receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2 receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2 receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2 receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2 receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1A and AT2 receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.

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.

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.

Angiotensin II regulates renin gene expression

1990 ◽  
Vol 259 (6) ◽  
pp. F882-F887 ◽  
Author(s):  
D. W. Johns ◽  
M. J. Peach ◽  
R. A. Gomez ◽  
T. Inagami ◽  
R. M. Carey
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Messenger Rna ◽  
Specific Activity ◽  
Ang Ii ◽  
Renal Vasculature ◽  
Osmotic Minipump ◽  
Renin Gene ◽  
Renin Mrna ◽  
Enalapril Treatment

We investigated the effect of angiotensin II (ANG II) and enalapril on accumulation of renin messenger RNA (mRNA) and on renal renin distribution (immunohistochemical analysis). Adult Wistar-Kyoto rats received enalapril (0.2 mg/ml) in distilled drinking water for 8 or 12 days. On day 5 of enalapril treatment, an osmotic minipump was implanted in the peritoneum that caused sustained release of ANG II (200 ng.kg-1.min-1) or vehicle (bovine serum albumin) for 3 or 7 days. Control rats received water for 8 or 12 days and osmotic minipump implantation (containing vehicle solution) on the 5th day. Renin mRNA was identified by hybridization with a 32P-labeled full-length complementary DNA and was detected by autoradiography. Enalapril treatment increased renal renin mRNA specific activity (renin mRNA/total RNA). Subsequent infusion of angiotensin II for 3 or 7 days decreased renal renin mRNA specific activity. In addition, renin immunostaining increased along the afferent arteriole after enalapril treatment; however, enalapril-induced spread of renin immunostaining was not inhibited by ANG II. Thus ANG II attenuates the accumulation of renin mRNA stimulated by enalapril treatment without alteration of renal renin distribution. The lack of effect of ANG II on renal renin distribution may be due to the length of turnover time for stored protein. These findings suggest the shortloop negative feedback of ANG II on renin reflects inhibition of renin synthesis by ANG II. Therefore, we propose that ANG II exerts a direct inhibitory effect on renin by regulation of renin gene expression in renal vasculature.

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