scholarly journals Renal interactions of renin-angiotensin system, nitric oxide and superoxide anion: implications in the pathophysiology of salt-sensitivity and hypertension

2009 ◽  
pp. S55-S68
Author(s):  
L Kopkan ◽  
L Červenka
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Kidney Function ◽  
Superoxide Anion ◽  
Renin Angiotensin System ◽  
Salt Sensitivity ◽  
Regulatory Function ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Enhanced Production

Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O(2)(-)) formation. Although the involvement of O(2)(-) production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O(2)(-) in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O(2)(-) acts as vasoconstrictor and enhances tubular sodium reabsorption. Nitric oxide (NO), another important radical that exhibits opposite effects than O(2)(-), is also involved in the regulation of kidney function. O(2)(-) rapidly interacts with NO and thus, when O(2)(-) production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O(2)(-) and NO generation, it has been suggested that physiological interactions of RAS, NO and O(2)(-) provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension.

scholarly journals Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats

Life Sciences ◽  
2020 ◽  
Vol 251 ◽  
pp. 117640 ◽  
Author(s):  
M. Nascimento ◽  
G.R. Punaro ◽  
R.S. Serralha ◽  
D.Y. Lima ◽  
M.G. Mouro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
P2x7 Receptor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Preoperative Renin-Angiotensin System Inhibitors Protect Renal Function in Aging Patients Undergoing Cardiac Surgery

2011 ◽  
Vol 167 (2) ◽  
pp. e63-e69 ◽  
Author(s):  
Viachaslau Barodka ◽  
Scott Silvestry ◽  
Ning Zhao ◽  
Xiangyin Jiao ◽  
David J. Whellan ◽  
...  
Keyword(s):  
Renal Function ◽  
Cardiac Surgery ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract 356: A Role for Renal Proximal Tubule Sodium Bicarbonate Cotransporter SLC4A5 in Salt-Sensitivity of Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Julia M Carlson ◽  
John J Gildea ◽  
Helen E McGrath ◽  
Robin A Felder
Keyword(s):  
Sodium Bicarbonate ◽  
Proximal Tubule ◽  
Mrna Expression ◽  
Cell Lines ◽  
Renin Angiotensin System ◽  
Salt Sensitivity ◽  
Renal Proximal Tubule ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Homozygous Variant

SLC4A5 is a sodium-bicarbonate co-transporter involved with sodium homeostasis. Based on unpublished data, two SLC4A5 single nucleotide polymorphisms (SNPs rs1017783 and rs7571842) have been highly associated with an individual’s salt-sensitivity status. Since the renal proximal tubule (RPT) regulates a large percentage of renal sodium transport, we investigated whether SLC4A5 was present in this nephron segment. Using confocal immunofluorescence microscopy, we found expression of SLC4A5 in human RPT cell plasma membrane and intracellular membrane vesicles. We then examined the physiologic implications of the SLC4A5 SNPs in human RPT cells. Using immunoblotting and RT-PCR, we found no significant differences in basal SLC4A5 expression in RPT cells between individuals that are homozygous variant at both SNPs and individuals that are wild-type (WT) for both alleles. Stimulation of the dopaminergic system with 1μM fenoldopam, or the renin-angiotensin system with 10 nM angiotensin II or 10 nM angiotensin III (n=18 per treatment) over 3 and 24 hours did not significantly alter SLC4A5 protein or 24 hour mRNA expression. These data indicate that SLC4A5 is not directly regulated by either the renal dopaminergic or renin-angiotensin system. However, 24 hour stimulation with the sodium ionophore monensin (MON, 1μM) significantly increased overall mRNA expression of SLC4A5 by 182±0.098% over vehicle (VEH) (ΔCq VEH=0.283±0.035; n=18, p<0.001). There was also a significant increase in SLC4A5 mRNA in three cell lines homozygous variant for both alleles compared to three WT cell lines following MON treatment at both 3 hours (138±0.10%; ΔCq WT MON = 0.5±0.052; n=9, p<0.05) and 24 hours (161±0.11%; ΔCq WT MON = 0.39±0.066; n=9, p<0.02). Three but not 24 hour stimulation with MON also significantly increased overall expression of SLC4A5 protein (137±0.00041%; RFU VEH=0.0030±0.00022; n=18, p<0.01). MON, by allowing salt to enter a cell, may be activating an enhancer that leads to increased transcription of SLC4A5 mRNA that is more effective in homozygous variant cell lines. These novel observations demonstrate that SNPs located in a non-promoter DNA intron are associated with enhanced promoter activity that is regulated by altered intracellular sodium.

scholarly journals Synergistic Expression of Angiotensin-Converting Enzyme (ACE) and ACE2 in Human Renal Tissue and Confounding Effects of Hypertension on the ACE to ACE2 Ratio

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2453-2457 ◽  
Author(s):  
Shigeyuki Wakahara ◽  
Tadashi Konoshita ◽  
Shinichi Mizuno ◽  
Makoto Motomura ◽  
Chikako Aoyama ◽  
...  
Keyword(s):  
Renal Function ◽  
Angiotensin Converting Enzyme ◽  
Pairwise Comparison ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Converting Enzyme ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Clinicopathological Variables

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

scholarly journals Hydrogen peroxide and nitric oxide induce anticontractile effect of perivascular adipose tissue via renin angiotensin system activation

Nitric Oxide ◽  
2019 ◽  
Vol 84 ◽  
pp. 50-59 ◽  
Author(s):  
Natália Nóbrega ◽  
Natália Ferreira Araújo ◽  
Daniela Reis ◽  
Larissa Moreira Facine ◽  
Claudiane Aparecida S. Miranda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Adipose Tissue ◽  
Renin Angiotensin System ◽  
Perivascular Adipose Tissue ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Activation

scholarly journals The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function

2018 ◽  
Vol 57 (22) ◽  
pp. 3241-3247 ◽  
Author(s):  
Takashi Matsuyama ◽  
Naro Ohashi ◽  
Sayaka Ishigaki ◽  
Shinsuke Isobe ◽  
Naoko Tsuji ◽  
...  
Keyword(s):  
Renal Function ◽  
Renin Angiotensin System ◽  
Dopamine System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Relationship
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