Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment

Meiracker, Anton H. van den; Veld, A. J. Man In't; Admiraal, P. J. J.; Eck, Henk J. Ritsema van; Boomsma, Frans; Derkx, F. H. M.; Schalekamp, M. A. D. H.

doi:10.1097/00004872-199208000-00015

Cited by 119 publications

(71 citation statements)

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“…27 Valsartan was generally well tolerated when added to an ACE inhibitor in this population. In both the 80 and 160 mg BID groups, hypotension did occasionally occur, but usually only after the first dose, while the patient was fasting and had already received lisinopril.…”

Section: Discussionmentioning

confidence: 82%

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

et al. 1999

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for the Vasodilator Heart Failure Trial (V-HeFT) Study Group* Background-ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heartfailure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects. Methods and Results-Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4-to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (Ϫ4.3 mm Hg; Pϭ0.16), pulmonary artery diastolic pressure (Ϫ4.7 mm Hg; Pϭ0.013), and systolic blood pressure (Ϫ6.8 mm Hg; Pϭ0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (Ϫ52.1 pg/mL; Pϭ0.001) and 160 mg BID (Ϫ47.8 pg/mL; PϽ0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (Ϫ97 pg/mL; Pϭ0.10). Seventy-four of the 83 patients completed the trial. Conclusions-Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.

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Section: Discussionmentioning

confidence: 82%

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

et al. 1999

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“…2,3 Second, ACE inhibitors continue to reduce BP even after plasma angiotensin II levels have returned to normal, a phenomenon known as angiotensin II escape. 4,5 In addition to the endothelium, large amounts of ACE are found in renal tissues. 6 This is especially true for the human kidney, which makes much more ACE than the kidneys of mice and rats.…”

mentioning

confidence: 99%

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

Giani

Janjulia

Kamat

et al. 2014

Journal of the American Society of Nephrology

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The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na + /H + exchanger 3, Na + /Pi co-transporter 2, phosphorylated Na + /K + /Cl 2 cotransporter, and phosphorylated Na + /Cl 2 cotransporter; and greater reductions in abundance and processing of the g isoform of the epithelial Na + channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition.

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“…The rationale behind dual RAAS blockade was initially based on data showing that ACEI monotherapy resulted in incomplete blockade with AI and renin accumulation and the subsequent 'escape' production of AII by non-ACE pathways. 7 Ménard et al 8 first reported a synergistic effect between ACE and ARB, albeit in a mouse model, and suggested that these two drug classes would overcome the escape phenomenon resulting from incomplete blockade. It was hoped that the addition of an ARB, by attenuating the 'AII escape', would provide a more complete blockade of the RAAS and that a complete blockade would translate into better BP control as well as incremental nephroprotective and cardioprotective effects.…”

Section: The Biologic Rationale For Dual Raas Blockadementioning

confidence: 99%

Is there benefit in dual renin– angiotensin–aldosterone system blockade? No, yes and maybe: A guide for the perplexed

Wong

2013

Diabetes and Vascular Disease Research

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Since the initial discovery of Angiotensin converting enzyme inhibitors (ACEI) in the 1960s and the launch of Captopril as the first available for clinical use in the 1970s, there now exist three other classes of drugs that block the renin angiotensin aldosterone system (RAAS): the angiotensin II receptor blockers (ARB), aldosterone antagonists (AA) and direct renin inhibitors (DRI). With the proven efficacy of RAAS blockers as monotherapy in many arenas there has been considerable interest in the use of dual therapy combinations of these medications that target different points in the pathway. By potentially offering a more complete RAAS blockade with a commensurate enhanced clinical effect, the strong biological rationale for dual therapy has led to it being embraced by clinicians as a treatment option, for hypertension and nephroprotection in particular. However, the initial enthusiasm for this treatment has been tempered by the recent results from several large trials such as ONTARGET and ALTITUDE, which do not support a specific dual therapy approach. In contrast, there is supportive evidence for dual blockade of specific combinations in selected patient groups and data are lacking for others. In the wake of this complex contemporary evidence, the conundrum now faced by clinicians committed to individualised care is, for which patients dual therapy could still be of benefit. This review examines for the practising clinician the current 'state of play' for dual blockade of various combinations and a perspective on its use in cardio-renal disease and diabetic complications.

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Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment

Cited by 119 publications

References 0 publications

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

Renal Angiotensin-Converting Enzyme Is Essential for the Hypertension Induced by Nitric Oxide Synthesis Inhibition

Is there benefit in dual renin– angiotensin–aldosterone system blockade? No, yes and maybe: A guide for the perplexed

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