AT2Receptor Blockade Reduces Cardiac Interstitial Cell DNA Synthesis and Cardiac Function After Rat Myocardial Infarction

Kuizinga, Marti C.; Smits, J. F. M.; Arends, Jan Willem; Daemen, M. J. A. P.

doi:10.1006/jmcc.1997.0607

Cited by 52 publications

(35 citation statements)

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“…The renin and Ang II response to the AT 2 receptor blockade was similar to the response observed during valsartan treatment and suggests that both AT 1 and AT 2 receptors have an inhibitory effect on the activity of the RAS. This result was unexpected because previous studies 7,8,10,15,28 demonstrated opposite effects for these 2 receptors. AT 2 receptor inhibition of renin synthesis and secretion is in agreement with its presumed vasodilator and cardiovascular protective effects.…”

Section: Discussionmentioning

confidence: 70%

“…4 -6 Currently, the AT 2 receptor has several described functions related to inhibition of cell growth, promotion of cell differentiation, and stimulation of apoptosis. [7][8][9][10][11][12] Previously, we demonstrated that during sodium depletion, the AT 2 receptor mediates renal production of bradykinin, nitric oxide (NO), and cGMP. [13][14][15][16][17] Unlike the well-known effect of AT 1 receptor on renin production, 18 -19 the influence of the AT 2 receptor on renal renin biosynthesis and Ang II production is not known.…”

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confidence: 99%

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Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

et al. 2005

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Abstract-Renin is regulated by angiotensin subtype 1 (AT 1 ) receptor, but it is unknown whether angiotensin subtype 2 (AT 2 ) receptor contributes to this regulation. We hypothesized that AT 2 receptors inhibit angiotensin II (Ang II) through inhibition of renin biosynthesis. We monitored changes in renal Ang II, renin mRNA and protein expression, and plasma renin concentration (PRC) in response to renal cortical administration of the AT 1 receptor blocker valsartan or the AT 2 receptor blocker PD 123319 (PD) in conscious rats administered low sodium intake (LS (Ang II) is the major effector hormone of the renin-angiotensin system (RAS). Most of the known physiological functions and pathologic effects associated with Ang II are mediated by the angiotensin subtype 1 (AT 1 ) receptor, including renin inhibition. 1 In contrast, the functions of the angiotensin subtype 2 (AT 2 ) receptor are still being elucidated. The AT 2 receptor is expressed abundantly during fetal development and declines after birth. [1][2][3] In mammalian adults, the AT 2 receptor had been reported in multiple organs, including the kidney. 4 -6 Currently, the AT 2 receptor has several described functions related to inhibition of cell growth, promotion of cell differentiation, and stimulation of apoptosis. [7][8][9][10][11][12] Previously, we demonstrated that during sodium depletion, the AT 2 receptor mediates renal production of bradykinin, nitric oxide (NO), and cGMP. [13][14][15][16][17] Unlike the well-known effect of AT 1 receptor on renin production, 18 -19 the influence of the AT 2 receptor on renal renin biosynthesis and Ang II production is not known.In this study, we tested the hypothesis that the AT 2 receptor inhibits renal renin synthesis and Ang II production. We used multiple techniques including renal interstitial microdialysis, [13][14][15][16][17] real-time quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and enzymelinked immunoassays for monitoring changes in renal Ang II, renin mRNA, renin protein expression, and plasma renin concentration to investigate whether intrarenal AT 2 receptors regulate renin production and Ang II formation. We monitored renal interstitial levels of Ang II in conscious rats during sodium restriction, a condition known to increase AT 2 receptor expression, and during AT 1 and AT 2 receptor blockade. 5 A distinct advantage of the microdialysis technique 13 is the ability to monitor renal Ang II levels in conscious rats without undesirable hemodynamic changes. In this study, we demonstrate for the first time to our knowledge that AT 2 receptors regulate the activity of the RAS through inhibition of renin biosynthesis in young rats. Methods Renal Microdialysis TechniqueFor the determination of renal interstitial fluid (RIF) Ang II, we constructed a microdialysis probe as previously described. [13][14][15][16][17] In vitro, best recovery for Ang II was observed with a perfusion rate of 3 L/min, and was Ϸ53%. Animal PreparationThe experiments were approved by the U...

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Section: Discussionmentioning

confidence: 70%

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confidence: 99%

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

et al. 2005

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“…We infused PD123319, the AT2 receptor antagonist, at a dose previously utilized for chronic infusion by osmotic mini-pump. (Kuizinga et al, 1998;Cao et al, 1999) To determine whether AT2 antagonism aected Angiotensin II-induced atherosclerosis in the absence of established disease, these drugs were coinfused into 2 month old mice in which the disease would have been minimal (Nakashima et al, 1994) We used a lower dose of Angiotensin II to attempt to maximize the dierences during co-infusion. Under these conditions, there was a striking enhancement of the development of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Antagonism of AT2 receptors augments Angiotensin II‐induced abdominal aortic aneurysms and atherosclerosis

Daugherty

Manning

Cassis

2001

British J Pharmacology

265

244

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; P=0.003). In contrast, the co-infusion of Angiotensin II with PD123319 resulted in a marked increase in the incidence and severity of aortic aneurysms. 3 To determine whether AT2 antagonism also promoted Angiotensin II-induced atherosclerosis, Angiotensin II was infused into young female apoE7/7 mice that had little spontaneous atherosclerosis. In these mice, co-infusion of PD123319 led to a dramatic increase in the extent of atherosclerosis. This increase was associated with no change in plasma lipid concentrations and only transient and modest increases in blood pressure during co-infusion with PD123319. 4 While antagonism of AT1 receptors totally prevented the formation of aneurysms, antagonism of AT2 receptors promoted a large increase in the severity of Angiotensin II-induced vascular pathology.

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“…34 Moreover, the cellular effects of angiotensin II are mediated by two structurally distinct receptor subtypes, angiotensin II type 1 and type 2 receptors, and angiotensin II type 1 and type 2 receptors have opposite functions. [35][36][37] It is also suspected that angiotensin II receptor stimulates the kininogenkinin system and induces cough; therefore it was interesting for us to examine the association between angiotensin II receptor polymorphisms and ACE-inhibitor-related cough. Our data indicate that there was no association between ACE, angiotensin II type 1 and type 2 receptor genotypes, and the occurrence of ACE-inhibitor-related cough; therefore, the common genetic variants of ACE, angiotensin II type 1 and type 2 receptors do not explain the occurrence of ACE-inhibitor-relatedcough.…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphisms of the renin–angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough

et al. 2002

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The use of angiotensin-converting enzyme (ACE) inhibitors to treat hypertension has recently increased. However, their use is associated with a persistent dry cough in a significant percentage of such patients. The present study was designed to assess the contribution of polymorphisms as a genetic marker of ACE-inhibitorrelated cough in a Japanese hypertensive population. Genotyping was carried out in 190 patients, 70 with cough and 120 without cough, who had been treated with ACE inhibitors. Polymorphisms of ACE insertion/ deletion (I/D), angiotensin II type 1 receptor (1166A/C), type 2 receptor (3123C/A), and bradykinin B2 receptor (À58T/C, exon 1, I/D), were analyzed in these subjects. The TT genotype and T allele of bradykinin B2 receptor (À58T/C) were identified at a significantly higher frequency in the cough (+) patients than in the cough (À) patients. This difference was even more pronounced in women. However, there was no significant relationship between polymorphisms of ACE, angiotensin II receptors, or bradykinin B2 receptor exon 1, and occurrence of ACE-inhibitor-related cough. The transcriptional activity of the bradykinin B2 receptor promoter is involved in the occurrence of cough, and this new marker may provide a valuable tool to detect patients at risk of developing this side effect of ACE inhibitors. In conclusion, Susceptibility to develop cough is associated with a genetic variant of the bradykinin B2 receptor promoter; thus, it may be possible to identify those patients who will develop this adverse reaction to ACE inhibitors in advance.

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AT2Receptor Blockade Reduces Cardiac Interstitial Cell DNA Synthesis and Cardiac Function After Rat Myocardial Infarction

Cited by 52 publications

References 0 publications

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

Angiotensin Subtype-2 Receptors Inhibit Renin Biosynthesis and Angiotensin II Formation

Antagonism of AT2 receptors augments Angiotensin II‐induced abdominal aortic aneurysms and atherosclerosis

Association of polymorphisms of the renin–angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough

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