Clinical Perspectives and Fundamental Aspects of Local Cardiovascular and Renal Renin-Angiotensin Systems

Mello, Walmor C. De; Fröhlich, Edward D.

doi:10.3389/fendo.2014.00016

Cited by 40 publications

(49 citation statements)

References 123 publications

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“…The possibility that the change in the inward calcium current be due to the secretion of Ang (1-7) and consequent activation of Mas receptors located extracellularly at the cell membrane, was ruled out because in cells exposed to A-779 added to the extracellular fluid, no change in the effect of intracellular Ang (1-7) was found. The increment of inward calcium current caused by intracellular Ang (1)(2)(3)(4)(5)(6)(7) contrasts with the small effect of Ang (1-7) administered extracellularly (not shown) confirming previous studies showing no influence of Ang (1-7) on calcium transients in cardiomyocytes [23,24]. Intracellular Ang (1-7) also increased the rate of I Ca inactivation which is known to influence the duration of the plateau of the action potential and the cardiac excitability.…”

Section: Discussionsupporting

confidence: 82%

“…Evidence is available, for instance, that the Mas receptor is internalized when activated by Ang (1-7) [17] what lead us to think that the presence of Ang (1)(2)(3)(4)(5)(6)(7) in the nucleus and perinuclear compartment may be related to internalization of the Mas/ Ang (1-7) complex. Furthermore, internalization of Ang (1-7) can be also produced by megalin which is a scavenger receptor [12,28].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of components of the renin-angiotensin system in different cells [1,2] lead to the suspicion that there is an intracrine renin-angiotensin aldosterone system (RAAS)-a concept substantiated by the finding that the intracellular administration of Ang II causes a severe impairment of cell communication and a change of the inward calcium current [3,4] in the heart. The decrease of gap junction communication induced by intracellular Ang II was blocked by losartan [3] administered into the cytosol revealing the role of an intracellular AT1 receptor in the decoupling action of the peptide.…”

Section: Introductionmentioning

confidence: 99%

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Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation

Mello

2015

Mol Cell Biochem

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The influence of intracellular administration of angiotensin (1-7) (Ang 1-7) on the inward calcium current was investigated in myocytes isolated from the left ventricle of Wistar Kyoto rat hearts using the patch-clamp technique. The results indicated: (1) the intracellular administration of Ang (1-7) (100 nM) enhanced the peak inward calcium current (I Ca); (2) the intracellular administration of A779 (100 nM) which a Mas receptor inhibitor, abolished the effect of Ang (1-7) on the calcium current; (3) the activation of PKA and consequent phosphorylation of calcium channels seems to be the mechanism involved in the increment of calcium current induced by the heptapeptide because the intracellular dialysis of the PKA inhibitor suppressed the effect of the heptapeptide; (4) the effect of Ang (1-7) was not related to its secretion into the extracellular space; (5)intracellular dialysis of Ang II (100 nM) has an opposite effect and reduced the peak I Ca; (6) extracellular administration of Ang II (100 nM) to cells previously dialyzed with Ang (1-7) also reduced the peak I Ca previously enhanced by Ang (1-7); and (7) intracellular Ang (1-7) reduced the heart cell volume. Implications for heart contractility were discussed.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation

Mello

2015

Mol Cell Biochem

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“…In addition, the RAS is known to play an essential role in the pathogenesis of several types of cardiovascular disease as well as in cardiac remodeling [17,18]. Growing evidence reveals that in addition to the classic systemic RAS, a local RAS operates, in organs such as the heart, large arteries, kidneys, and even in single cells to further modulate cardiovascular regulation [19,20]. In the RAS, the precursor protein angiotensinogen (AGT) is first converted into angiotensin I (Ang I) by renin (Ren).…”

Section: Introductionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

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Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

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“…Local RAS activation and its components lead to structural and functional changes in kidney cells, which are independent of those elicited by the classical renin-angiotensin endocrine system (12). Local intracrine/intracellular ANG II is profoundly involved in cell proliferation, oxidative stress, nitric oxide production, and electrolyte metabolism (53).…”

mentioning

confidence: 99%

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

Wang

Luo

Lin

et al. 2015

American Journal of Physiology-Renal Physiology

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Ureteral obstruction is associated with reduced expression of renal aquaporins (AQPs), urinary concentrating defects, and an enhanced inflammatory response, in which the renin-angiotensin system (RAS) may play an important role. We evaluated whether RAS blockade by a direct renin inhibitor, aliskiren, would prevent the decreased renal protein expression of AQPs in a unilateral ureteral obstruction (UUO) model and what potential mechanisms may be involved. UUO was performed for 3 days (3UUO) and 7 days (7UUO) in C57BL/6 mice with or without aliskiren injection. In 3UUO and 7UUO mice, aliskiren abolished the reduction of AQP2 protein expression but not AQP1, AQP3, and AQP4. mRNA levels of renal AQP2 and vasopressin type 2 receptor were decreased in obstructed kidneys of 7UUO mice, which were prevented by aliskiren treatment. Aliskiren treatment was also associated with a reduced inflammatory response in obstructed kidneys of UUO mice. Aliskiren significantly decreased mRNA levels of several proinflammatory factors, such as transforming growth factor-β and tumor necrosis factor-α, seen in obstructed kidneys of UUO mice. Interestingly, mRNA and protein levels of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β were dramatically increased in obstructed kidneys of 7UUO mice, which were significantly suppressed by aliskiren. In primary cultured inner medullary collecting duct cells, IL-1β significantly decreased AQP2 expression. In conclusions, RAS blockade with the direct renin inhibitor aliskiren increased water channel AQP2 expression in obstructed kidneys of UUO mice, at least partially by preventing NLRP3 inflammasome activation in association with ureteral obstruction.

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Clinical Perspectives and Fundamental Aspects of Local Cardiovascular and Renal Renin-Angiotensin Systems

Cited by 40 publications

References 123 publications

Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation

Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

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