Angiotensin II infusion improves renal function in experimental hyperdynamic sepsis

ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.

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Role of angiotensin II in the altered renal function of congestive heart failure.

Circulation Research ◽

10.1161/01.res.55.5.669 ◽

1984 ◽

Vol 55 (5) ◽

pp. 669-675 ◽

Cited By ~ 131

Author(s):

I Ichikawa ◽

J M Pfeffer ◽

M A Pfeffer ◽

T H Hostetter ◽

B M Brenner

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Renal Function ◽

Angiotensin Ii

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Effects of combination therapy with angiotensin II type I receptor blockers and calcium channel blockers on renal function in hypertensive patientsA retrospective, “real-world” comparative study

Arzneimittelforschung ◽

10.1055/s-0031-1296250 ◽

2011 ◽

Vol 60 (02) ◽

pp. 64-70 ◽

Cited By ~ 1

Author(s):

Harutaka Yamada ◽

Norihiro Suga ◽

Kunihiro Maeda ◽

Yukihiro Kimura ◽

Naoto Miura ◽

...

Keyword(s):

Renal Function ◽

Angiotensin Ii ◽

Combination Therapy ◽

Comparative Study ◽

Calcium Channel ◽

Real World ◽

Calcium Channel Blockers ◽

Channel Blockers ◽

Type I ◽

Receptor Blockers

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Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽

10.1161/hyp.60.suppl_1.a7 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Quaisar Ali ◽

Yonnie Wu ◽

Tadashi Inagami ◽

Tahir Hussain

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Angiotensin Ii ◽

Renin Activity ◽

Ang Ii ◽

Male And Female ◽

Female Mice ◽

Gender Specific

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

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Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00328.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. G313-G321 ◽

Cited By ~ 3

Author(s):

Mads Israelsen ◽

Emilie Kristine Dahl ◽

Bjørn Stæhr Madsen ◽

Signe Wiese ◽

Flemming Bendtsen ◽

...

Keyword(s):

Renal Function ◽

Angiotensin Ii ◽

Vascular Resistance ◽

Impaired Renal Function ◽

Combined Treatment ◽

Suppressive Effect ◽

Peripheral Vascular Resistance ◽

Decompensated Cirrhosis ◽

Peripheral Vascular ◽

Renin Angiotensin

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, P < 0.01) but had no significant effects on GFR. Renin ( P < 0.05), angiotensin II ( P < 0.005), and aldosterone ( P < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min−1·m−2, P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (−0.92 L/min, P < 0.005) and renin ( P < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P < 0.05) and increased renin ( P < 0.005), angiotensin II ( P < 0.005), and aldosterone ( P < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites. NEW & NOTEWORTHY This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.

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