Renin inhibition: the holy grail of renin–angiotensin system blockade?

McInnes, Gordon T.

doi:10.1038/sj.jhh.1002221

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…In addition, PRA is an independent risk factor of myocardial infarction in hypertensive patients and microvascular complications in patients with diabetes mellitus [34]. Furthermore, Ang II causes an increase in vascular resistance and blood pressure because of its powerful vasoconstrictor effect, its effect on catecholamine levels [35] and its aldosterone-inducing effects [36].…”

Section: Discussionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

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Background: Interrupting the renin-angiotensin system (RAS) with an angiotensin II receptor blocker (ARB) has been found to induce RAS overactivation. In this study, we investigated the effect of 2 calcium channel blockers (CCBs), cilnidipine (L-/N-type CCB) and amlodipine (L-type CCB), on the RAS activation induced by an ARB in a strain of spontaneously hypertensive rats (SHR/Izm, 10 weeks of age). Methods: Rats intravenously catheterized for blood collection were randomly divided into groups that were administered the vehicle, the ARB valsartan or valsartan combined with one of the 2 CCBs. Their blood and kidneys were collected 270 min after administration. Results: Valsartan increased the plasma angiotensin II (Ang II) level in a dose-dependent manner. Cilnidipine suppressed the increase in plasma renin activity and plasma Ang II levels induced by valsartan, but amlodipine did not. Combined administration of cilnidipine, but not amlodipine, and valsartan significantly reduced the noradrenaline content in the renal cortex. Conclusions: The results of this study suggest that the suppressive effect of cilnidipine on the valsartan-induced increase in RAS activity can be partly explained by its sympatholytic action mediated by N-type calcium channel blockade, and that combined administration of cilnidipine and valsartan might provide a synergistic therapeutic effect.

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Section: Discussionmentioning

confidence: 99%

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Aritomi

Niinuma²,

Ogawa³

et al. 2011

Am J Nephrol

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“…However, while concern about the escape phenomena usually focuses on the return of angiotensin II to pretreatment levels, the decreased PRA may be equally or more important since pre-treatment PRA is an independent risk factor for myocardial infarction in hypertensive patients and for microvascular complications in diabetes (McInnes 2007). Although aliskiren increases plasma renin concentrations, PRA remains suppressed because cleavage of angiotensinogen is blocked.…”

Section: The Future Of Aliskirenmentioning

confidence: 99%

The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction

Verdecchia

Angeli²,

Mazzotta³

et al. 2008

VHRM

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An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.

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“…Other studies have examined aliskiren's effect on surrogate heart failure, diabetic, and renal end points. 34,36,37 There are no published long-term clinical outcome trials but several have been proposed and are underway, with many funded by the drug's manufacturer. 23,36 Aliskiren trial in type 2 diabetes using cardiorenal end points (ALTITUDE) will randomize 8600 patients with type II diabetes and either a history of cardiovascular disease (myocardial infarction, stroke, heart failure, or coronary artery disease) or microalbuminuria/diabetic nephropathy to placebo or aliskiren 300 mg daily.…”

Section: Direct Renin Inhibitorsmentioning

confidence: 99%

“…34,36,37 There are no published long-term clinical outcome trials but several have been proposed and are underway, with many funded by the drug's manufacturer. 23,36 Aliskiren trial in type 2 diabetes using cardiorenal end points (ALTITUDE) will randomize 8600 patients with type II diabetes and either a history of cardiovascular disease (myocardial infarction, stroke, heart failure, or coronary artery disease) or microalbuminuria/diabetic nephropathy to placebo or aliskiren 300 mg daily. 38 The primary end point consists of a composite of both cardiovascular and renal events associated with diabetes including cardiovascular death and resuscitated death, nonfatal myocardial infarction, nonfatal stroke, unplanned hospitalization for heart failure, end-stage renal disease or renal death or doubling of baseline serum creatinine concentration.…”

Section: Direct Renin Inhibitorsmentioning

confidence: 99%

Review: Update on Newer Antihypertensive Medicines and Interventions

Gerstenblith

2010

J Cardiovasc Pharmacol Ther

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The incidence and prevalence of systemic hypertension are reaching global epidemic proportions. Despite a diverse pharmacologic armamentarium of agents to treat high blood pressure, suboptimal control remains a significant problem in as many as 43% of patients and this rate has not significantly improved over the past 2 decades. There are a variety of factors contributing to this including patient nonadherence due to complex drug regimens and medication side effects, undertreatment, and treatment resistance. There, thus, remains a need to develop novel agents and approaches to antihypertensive therapy that facilitate attainment of optimal blood pressure levels. This monograph will review a number of new pharmacologic targets and interventions as well as a novel method of drug delivery to patients.

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Renin inhibition: the holy grail of renin–angiotensin system blockade?

Cited by 9 publications

References 26 publications

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback

The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction

Review: Update on Newer Antihypertensive Medicines and Interventions

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