New angiotensins

Varagić, Jasmina; Trask, Aaron J.; Jessup, Jewell A.; Chappell, Mark C.; Ferrario, Carlos M.

doi:10.1007/s00109-008-0340-4

Cited by 70 publications

(74 citation statements)

References 102 publications

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“…15 In various tissues, including the heart and kidneys, the concentration of proang-12 is much higher than those of Ang I and Ang II. 8,9,16 By contrast, the concentration of proang-12 in plasma is lower than that of either Ang I or Ang II. This suggests that proang-12 may be a component of only the tissue RAS in rats.…”

Section: Introductionmentioning

confidence: 95%

“…The vasoconstrictor and pressor effects of proang-12 are abolished by ACE inhibitors and angiotensin receptor blockers, which suggests ACE is involved in the conversion of proang-12 to Ang II. [8][9][10] However, Prosser et al 11,12 reported that chymase inhibition attenuates proang-12-induced cardiac damage caused by ischemia-reperfusion in rat hearts ex vivo, as well as proang-12-induced constriction of isolated rat arteries. This suggests that chymase is also involved in the conversion of proang-12 to Ang II.…”

Section: Introductionmentioning

confidence: 99%

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Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

et al. 2011

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It has been suggested that proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, may function as a component of the tissue renin-angiotensin system (RAS). To investigate the role of proang-12 in the production of angiotensin II (Ang II), we measured its plasma and tissue concentrations in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, with and without RAS inhibition. The 15-week-old male WKY and SHR rats were left untreated or were treated for 7 days with 30 mg kg À1 per day losartan, an angiotensin receptor blocker, or with 20 mg kg À1 per day imidapril, an angiotensin-converting enzyme (ACE) inhibitor. Both treatments increased renin activity and the concentrations of angiotensin I (Ang I) and Ang II in the plasma of WKY and SHR rats, but neither affected plasma proang-12 levels. In contrast to the comparatively low level of proang-12 seen in plasma, cardiac and renal levels of proang-12 were higher than those of Ang I and Ang II. In addition, despite activation of the RAS in the systemic circulation, tissue concentrations of proang-12 were significantly reduced following treatment with losartan or imidapril. Similar reductions were also observed in the tissue concentrations of Ang II in both strains, without a reduction in Ang I. These results suggest that tissue concentrations of proang-12 and Ang II are regulated independently of the systemic RAS in WKY and SHR rats, which is consistent with the notion that proang-12 is a component of only the tissue RAS.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

et al. 2011

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“…Intracellular cross-talk between mineralocorticoid and AT1 receptors provides another theoretical basis for the combined therapy with MRBs and ARBs (Figure 1). Finally, the appreciation that there are other effects of angiotensin II (48) or specific effects of some ARBs that are not mediated through classical AT-1 receptors (37,49,50) suggests a theoretical advantage of using MRBs with ARBs rather than ACEIs. ARBs are currently more expensive than ACEIs (51), but generic ARBs may become available in 2010, so cost should have less influence on clinical decision making.…”

Section: Combinations Of Mrbs With Other Inhibitors Of the Raasmentioning

confidence: 99%

Mineralocorticoid Receptor Blockers and Chronic Kidney Disease

Jain

Campbell

Warnock

2009

Clinical Journal of the American Society of Nephrology

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The increasing prevalence of chronic kidney disease (CKD) and the public health initiatives for detection and slowing its progression have placed special emphasis on controlling proteinuria and the renin-angiotensin-aldosterone system (RAAS). In addition to the traditional blockers of angiotensin-converting enzyme and angiotensin receptors, mineralocorticoid receptor blockers (MRBs) have come into focus as anti-proteinuric agents with moderate anti-hypertensive effects. The beneficial effects of MRBs on mortality in patients with cardiac disease have been well described. We review the role of aldosterone in end-organ damage, the rationales for using MRBs as adjuncts to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in treating CKD, and the adverse effects that may occur when these agents are used in combination. Suggestions are included for avoiding serious adverse events in CKD patients treated with MRBs. There is a clearly defined need for prospective outcome studies focused on cardiovascular mortality as well as progression of CKD in patients treated with MRBS and other inhibitors of the RAAS.Clin J Am Soc Nephrol 4: 1685 -1691, 2009 . doi: 10.2215 T here are compelling indications for the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in treating patients with chronic kidney disease (CKD), hypertension, and proteinuria, with the expressed goal of preventing progression to ESRD (1). Proteinuria appears to be an independent predictor of renal and cardiovascular outcomes (2,3). Anti-proteinuric therapy is an important part of treatment for slowing progression of CKD (4,5).Increased aldosterone levels are seen in patients treated with ACEIs and ARBs ("escape" or "breakthrough"), supporting the use of MRBs as adjuncts to ACEIs or ARBs (6 -8). As summarized in two recent meta-analyses (9,10), adding MRBs to ACEIs or ARBs: a) reduces proteinuria; b) hyperkalemia can be clinically significant when the estimated GFR (eGFR) is Ͻ30 ml/min/1.73 m 2 , when other drugs that increase serum potassium are used, and when oral potassium supplements are given; and c) the long-term effects of combined therapy on renal outcomes and mortality need to be defined.Randomized controlled trials demonstrate a beneficial effect of adding MRBs to ACEIs or ARBs on survival in patients with left ventricular dysfunction (11,12). MRBs are now widely used in many patients with less severe heart disease, although the supporting evidence is not as strong as for the severe heart failure studies (13). The beneficial cardiac effects of MRBs have not been demonstrated in patients with eGFR Ͻ60 ml/min/ 1.73 m 2 . Recent work has explored the cellular mechanisms of interactions between mineralocorticoid and angiotensin II, type I (AT-1) receptors. Our purpose is to review this information, provide rationales for using MRBs in combination with other inhibitors of the RAAS, and to better define the potential benefits and risks of combined therapy in CKD patients....

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“…Previous studies suggested that the ACE2-Ang 1-7 axis has an important role in hypertensive disease and CHF. [7][8][9] Takeda et al 10 reported that treatment with candesartan increased ACE2 mRNA level and decreased angiotensinogen mRNA level in the heart. Recently, it was shown that olmesartan increased ACE2 expression during the remodeling of the heart after myocardial infarction, 11 and olmesartan improved left ventricular remodeling with an increase in cardiac ACE2 expression in stroke-prone spontaneously hypertensive rats.…”

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confidence: 99%

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

et al. 2009

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In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB. A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n¼25): continuous candesartan treatment at a stable dose; and olmesartan group (n¼25): candesartan (8 mg day À1 ) was changed to olmesartan given at a dose of 20 mg day À1 . There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135 ± 36 vs. 123 ± 29 g m À2 ; Po0.01). These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

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New angiotensins

Cited by 70 publications

References 102 publications

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system

Mineralocorticoid Receptor Blockers and Chronic Kidney Disease

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

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