Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Sata, Naoyuki; Tanaka, Yasuhiro; Suzuki, Syusaku; Kamimura, Ryouzou; Mifune, Hiroharu; Nakamura, Kazuo; Miyahara, Kenkichi; Arima, Terukatsu

doi:10.1253/circj.67.1053

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Thus we postulate that the up-regulation of ANP gene expression that we observed in vitro after blocking both AT 1 and AT 2 receptors could have been due to the conversion of AngII into Ang- (1)(2)(3)(4)(5)(6)(7). This is also consistent with the report that ACEi and ARB directly stimulate ANP secretion in vivo [28].…”

Section: Discussionsupporting

confidence: 92%

Angiotensin-converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1–7)

et al. 2012

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Deficiency of ACE2 (angiotensin-converting enzyme 2), which degrades Ang (angiotensin) II, promotes the development of glomerular lesions. However, the mechanisms explaining why the reduction in ACE2 is associated with the development of glomerular lesions have still to be fully clarified. We hypothesized that ACE2 may regulate the renoprotective actions of ANP (atrial natriuretic peptide). The aim of the present study was to investigate the effect of ACE2 deficiency on the renal production of ANP. We evaluated molecular and structural abnormalities, as well as the expression of ANP in the kidneys of ACE2-deficient mice and C57BL/6 mice. We also exposed renal tubular cells to AngII and Ang-(1-7) in the presence and absence of inhibitors and agonists of RAS (renin-angiotensin system) signalling. ACE2 deficiency resulted in increased oxidative stress, as well as pro-inflammatory and profibrotic changes. This was associated with a down-regulation of the gene and protein expression on the renal production of ANP. Consistent with a role for the ACE2 pathway in modulating ANP, exposing cells to either Ang-(1-7) or ACE2 or the Mas receptor agonist up-regulated ANP gene expression. This work demonstrates that ACE2 regulates renal ANP via the generation of Ang-(1-7). This is a new mechanism whereby ACE2 counterbalances the renal effects of AngII and which explains why targeting ACE2 may be a promising strategy against kidney diseases, including diabetic nephropathy.

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Section: Discussionsupporting

confidence: 92%

Angiotensin-converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1–7)

et al. 2012

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“…The natriuretic peptides were significantly reduced by eprosartan during the entire study day. This contrasts with other reports on the effect of AT1 blockade on concentrations of ANP, as ANP increased after treatment with irbesartan for 30 days in patients with essential hypertension [37] and also after administration of candesartan for 8 weeks in the rat [38]. The reason for this discrepancy is unclear, but could be related to fact that we evaluated only the very short term effect of eprosartan during sodium restriction.…”

Section: Discussioncontrasting

confidence: 83%

Eprosartan modulates the reflex activation of the sympathetic nervous system in sodium restricted healthy humans

Vase

Lauridsen

Bech

et al. 2008

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• A sympatho-inhibitory effect of ACE-inhibitors and AT1 receptor antagonists has been widely demonstrated in animal models, but in humans this effect tends only to be present during chronic treatment in conditions with pre-existing high levels of sympathetic activity.• Sodium restriction increases renal sympathetic nerve activity and the activity of the renin-angiotensin system and may be a favourable condition to demonstrate sympatho-inhibition as a short-term effect of the AT1 receptor antagonist eprosartan in healthy humans. WHAT THIS STUDY ADDS• Results from our study indicate that during sodium restriction eprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. • During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex. AIMSTo test the hypothesis that eprosartan inhibits both nonbaroreflex and arterial baroreflex mediated activation of the sympathetic nervous system, assessed by renal tubular function, systemic haemodynamics and vasoactive hormones, in sodium restricted healthy humans. METHODSThe effect of eprosartan on urinary sodium, lithium and water excretion, heart rate (HR), blood pressure and vasoactive hormones was measured before, during and after a cold pressor test (CPT) and sodium nitroprusside (SNP) infusion in a randomized, placebo controlled, double-blind, crossover study in 17 healthy subjects. Glomerular filtration rate and renal tubular function were determined by a continuous infusion clearance technique and vasoactive hormones by radioimmunoassays. RESULTSEprosartan attenuated the impact of the CPT on HR (mean difference from placebo (95% confidence interval) (3.9 (0.7, 7.0) min) and mean arterial pressure (MAP) (4.7 (0.3, 9.2) mmHg), but no effect of eprosartan was observed on the impact of the CPT on renal tubular function. During a SNP induced reduction in MAP of 10 mmHg eprosartan decreased fractional excretions of sodium (0.46 (0.14, 0.76)%) and lithium (5.1 (2.5, 7.6)%) and tended to increase HR (4.1 (-0.26, 8.4) min -1 ) and plasma concentrations of norepinephrine (33.8 (-5.8, 72.1) pg ml CONCLUSIONSThese findings suggest that during mild sodium restriction eprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex.

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“…In SHRs, a reduction in body weight (−14%) was only found after 30 mg/kg/day candesartan given over 6 weeks (Kohya et al 1995). However, findings from high-dose candesartan (≥10 mg/kg/ day) applications were discrepant regarding body weight in Wistar rats, since two studies revealed a reduction in body weight (Mukawa et al 2003;Zorad et al 2006) and two others described those doses as ineffective (Igarashi et al 2001;Sata et al 2003). In our study, the body weight was reduced in SHR selectively after the highest dose of candesartan (16 mg/kg/day).…”

Section: Discussionmentioning

confidence: 99%

Weight loss and hypophagia after high-dose AT1-blockade is only observed after high dosing and depends on regular leptin signalling but not blood pressure

Müller-Fielitz

Markert

Wittmershaus

et al. 2011

Naunyn-Schmied Arch Pharmacol

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AT(1)-blockade has been shown to induce weight loss in animals or patients. The aim of this study was to investigate whether weight reduction after AT(1)-blockade is dependent on dose, blood pressure reduction and leptin signalling. Spontaneously hypertensive rats (SHR) and lean and obese Zucker rats were treated for 4 weeks with candesartan (0, 2, 6 or 16 mg/kg/day). Body weight, food intake and hypothalamic mRNA levels of (an)orexigenic peptides were determined. Obese Zucker rats served as a model of primary leptin resistance. In SHR, body mass index and food intake were decreased selectively by 16 mg/kg/day candesartan but not after using normal (2 mg/kg/day) or supranormal (6 mg/kg/day) doses. Correlation analysis between blood pressure and body weight indicated no relationship of hypotensive potency on weight loss. The hypothalamic mRNA levels of the orexigenic peptide MCH (melanin-concentrating hormone) were diminished in parallel. Consistent to the results in SHRs, 16 mg/kg/day candesartan revealed a decrease of body weight, food intake and hypothalamic MCH mRNA levels in lean Zucker rats. In obese Zucker rats, none of these parameters were reduced by candesartan. Loss of body weight and hypophagia are not general features of AT(1)-blockers, since neither was seen after normal or moderately supranormal doses, but they were, after the highest doses. These actions of AT(1)-blockers occur independently of their ability to lower blood pressure. They do depend on an intact leptin signalling, since they were absent in obese Zucker rats that feature a genetic mutation of the leptin receptor.

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Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Cited by 9 publications

References 31 publications

Angiotensin-converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1–7)

Angiotensin-converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1–7)

Eprosartan modulates the reflex activation of the sympathetic nervous system in sodium restricted healthy humans

Weight loss and hypophagia after high-dose AT1-blockade is only observed after high dosing and depends on regular leptin signalling but not blood pressure

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