Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers: Evidence for and against the combination in the treatment of hypertension and proteinuria

Andersen, Niels Holmark; Mogensen, Carl Erik

doi:10.1007/s11906-002-0070-x

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…Among the potential mediators of mesangial matrix expansion in diabetic nephropathy, the peptide ANG II is particularly outstanding, and many lines of evidence suggest activation of the intrarenal renin-angiotensin system (RAS) in diabetes (21). The RAS has been extensively studied in diabetes, and strong evidence indicates that the inhibition of angiotensin-converting enzyme (ACE) and/or ANG II receptors delays the progression of diabetic nephropathy (3,37). Despite these benefits, the renoprotective effects of RAS inhibition cannot be fully explained only by the hemodynamic effects of the system causing a reduction in blood pressure.…”

mentioning

confidence: 99%

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Vidotti

Casarini

Cristovam

et al. 2004

American Journal of Physiology-Renal Physiology

199

175

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Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. The results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of (pro)renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. The increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. The consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.

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mentioning

confidence: 99%

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Vidotti

Casarini

Cristovam

et al. 2004

American Journal of Physiology-Renal Physiology

199

175

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“…[133] compared losartan with enalapril and obtained similar effects in a 1‐year study. The concept of dual blockade was used in the CALM study [134–135]. There was a similar effect on blood pressure and microalbuminuria of each drug, but interestingly with dual blockade there was a better effect on blood pressure and possibly microalbuminuria.…”

Section: Antihypertensive Treatment Ace‐inhibition and New Studies Omentioning

confidence: 99%

Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes*

Mogensen

2003

Journal of Internal Medicine

188

119

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. Mogensen CE (Aarhus University hospital, Aarhus C, Denmark). Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes (Review). J Intern Med 2003; 254: 45–66. Over the past decade, there has been considerable focus on the concept of microalbuminuria, not only because it predicts renal disease in type 1 and type 2 diabetes, but also because it relates to premature mortality in the diabetic and in the general population. More importantly, intervention at this stage is now possible with the perspective of preserving glomerular filtration rate (GFR) and ameliorating cardiovascular disease and ensuing strong end‐points. Initial studies. The concept of microalbuminuria was introduced about 20 years ago and since then there has been a multitude of studies and papers on this subject using the original definition, but not always, in the US. Before that time it was suggested, mainly from the US, that diabetic renal disease was an untreatable relentlessly progressive condition. Genetic studies. There is an overwhelming number of studies on genetics and diabetes and also covering the genetics of diabetic complications including nephropathy. However, so far the results are extremely disappointing. Patients at risk cannot be identified and genetic analyses are of no value as a guide to treatment. The notion that the development of complications is controlled mainly by a special genetic pattern is increasingly doubtful. In genetic studies, it is rather phenotypic well‐accepted risk factors that dominate. Structural basis of microalbuminuria. Patients with microalbuminuria have significant abnormalities in the kidney, including glomeruli. This is quite clear in patients with type 1 diabetes, but is also seen in type 2 diabetes, where on the other hand, other risk factors such as hypertension and dyslipidaemia also seem to be of importance, including loss of autoregulation. Renal biopsies are generally not indicated in the management of diabetic patients. Microalbuminuria and early mortality. It is quite clear that microalbuminuria predicts early mortality both in type 1 and type 2 diabetes. The association to other risk factors may partly explain this – but this does not account for the whole picture. Endothelial dysfunction as well as inflammatory and arteriosclerotic abnormalities in blood vessels may be a relevant hypothesis that needs to be further explored along with other possibilities. Clinical course and associated abnormalities. The risk factor for progression in normoalbuminuric patients to microalbuminuria is higher than normal albumin excretion (strongest factor), poor glycaemic control, elevated blood pressure, and to some extent smoking. The clinical course of microalbuminuria is usually progressive, but with the more effective intervention now available we encounter that the so‐called natural history (without intervention) is increasingly difficult to study. Microalbuminuria is clearly associated with a number of abnormalities, almost in all organs, but GFR is generally well p...

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“…Several clinical studies in normotensive and hypertensive patients with type I diabetes have demonstrated reduction of microalbuminuria with usual doses of ACE inhibitors, independent of BP reduction [52]. Trials evaluating the importance of dose in microalbuminuric patients with type I diabetes have been positive but few in number (Table 1).…”

Section: Microalbuminuriamentioning

confidence: 99%

“…What are the options in patients where despite highdose monotherapy proteinuria is still elevated? An alternative and appropriate strategy, based on limited data, is the combined use of ACE inhibitors and ARBs [52]. The difficulty in determining the effectiveness of this approach has been the tendency to combine very low or moderate doses of ACE inhibitors and ARBs together without first titrating the initial agent to its maximum [47,51,57].…”

Section: Optimal Renoprotective Dosementioning

confidence: 99%

How high should an ACE inhibitor or angiotensin receptor blocker be dosed in patients with diabetic nephropathy?

Weinberg

Kaperonis²,

Bakris

2003

Current Science Inc

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Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), two drug classes that effectively block the actions of the renin-angiotensin system (RAS), have unique capabilities as antihypertensive agents. Recent landmark clinical trials have demonstrated their important roles as primary therapy for the prevention of renal disease in diabetes. The optimal dosage of these RAS blockers required to slow the progression of renal disease or impair the development of cardiovascular risk is not known. However, data from many studies strongly support the use of the higher doses of ACE inhibitors or ARBs to reduce proteinuria. All studies of kidney disease progression demonstrate benefit on slowing only when blood pressure is reduced when using higher doses. In order to accrue the optimum benefit from ACE inhibitors and ARBs, the dose-response relationship for diabetic renal disease will have to be determined. The best strategy, ie, supramaximal doses of ACE inhibitors or ARBs or combining them, is still a matter of debate but may be resolved soon by results of ongoing studies.

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Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers: Evidence for and against the combination in the treatment of hypertension and proteinuria

Cited by 13 publications

References 44 publications

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes*

How high should an ACE inhibitor or angiotensin receptor blocker be dosed in patients with diabetic nephropathy?

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