Prediction of sustained antihypertensive efficacy of chronic captopril therapy: Relationships to immediate blood pressure response and control plasma renin activity

Waeber, Bernard; Gavras, Irène; Brunner, Hans R.; Cook, Courtney; Charocopos, Fotis; Gavras, Haralambos

doi:10.1016/0002-8703(82)90278-2

Cited by 33 publications

(13 citation statements)

References 16 publications

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“…Ang II formation occurring from chymase activity associated with the extracellular matrix in the cardiac interstitium may thus be a major site of local Ang II formation in the human heart. ACE inhibitors are widely used in the treatment of hypertension and congestive heart failure (2,3,42). Because it is presumed that Ang II levels in the failing heart are reduced substantially after ACE inhibitor therapy, some investigators believe that Ang II effects on the failing human heart are deleterious (6).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.

Urata¹,

Boehm²,

Philip³

et al. 1993

J. Clin. Invest.

373

230

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The human heart is a target organ for the octapeptide hormone, angiotensin II (Ang II). Recent studies suggest that the human heart contains a dual pathway of Ang II formation in which the major Ang II-forming enzymes are angiotensin I-converting enzyme (ACE) and chymase. Human heart chymase has recently been purified and its cDNA and gene cloned. This cardiac serine proteinase is the most efficient and specific Ang Il-forming enzyme described. To obtain insights into the cardiac sites of chymase-dependent Ang II formation, we examined the cellular localization and regional distribution of chymase in the human heart. Electron microscope immunocytochemistry using an anti-human chymase antibody showed the presence of chymase-like immunoreactivity in the cardiac interstitium and in cytosolic granules of mast cells, endothelial cells, and some mesenchymal interstitial cells. In the cardiac interstitium, chymase-like immunoreactivity is associated with the extracellular matrix. In situ hybridization studies further indicated that chymase mRNA is expressed in endothelial cells and in interstitial cells, including mast cells. Tissue chymase levels were determined by activity assays and by Western blot analyses. Chymase levels were approximately twofold higher in ventricles than in atria. There were no significant differences in chymase levels in ventricular tissues obtained from nonfailing donor hearts, failing ischemic hearts, or hearts from patients with ischemic cardiomyopathy. These findings suggest that a major site of chymase-dependent Ang II formation in the heart is the interstitium and that cardiac mast cells, mesenchymal interstitial cells, and endothelial cells are the cellular sites of synthesis and storage of chymase. In the human heart, because ACE levels are highest in the atria and chymase levels are highest in ventricles, it is likely that the relative contribution of ACE and chymase to cardiac Ang II formation varies with the cardiac chamber. Such differences may lead to differential suppression of cardiac Ang II levels during chronic ACE inhibitor therapy in patients with congestive heart failure. (J. Clin. Invest. 1993. 91:1269-1281.) Key words: angiotensin I-convert-A portion of these studies has been presented in abstract form at the

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Section: Discussionmentioning

confidence: 99%

“…Ang II is a vasoconstrictor hormone ( 1 ), and drugs that inhibit ACE are potent antihypertensive agents (2). ACE inhibitors are also very effective in the treatment of congestive heart failure (3,4).…”

Section: Introductionmentioning

confidence: 99%

Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.

Urata¹,

Boehm²,

Philip³

et al. 1993

J. Clin. Invest.

373

230

View full text Add to dashboard Cite

show abstract

“…[9][10][11] The acute change in BP correlates with pretreatment plasma renin activity and angiotensin levels, such that the greatest reductions in BP are seen in patients with the highest plasma renin activity. [12][13][14][15] In support of this, co-administration of drugs that increase plasma renin activity, such as diuretics, abolishes the racial differences in response to ACEis. 16 However, with long-term therapy, a greater percentage of patients achieve a decrease in BP, and the antihypertensive effect no longer correlates with pretreatment plasma renin activity.…”

Section: Angiotensin-converting Enzyme Inhibitorsmentioning

confidence: 91%

“…16 However, with long-term therapy, a greater percentage of patients achieve a decrease in BP, and the antihypertensive effect no longer correlates with pretreatment plasma renin activity. [13][14][15] The mechanism for this increased efficacy with chronic administration is not clear but may involve the kallikreinkinin system or production of vasodilatory prostaglandins. 16 One of the characteristics of ACEis is that they lower peripheral vascular resistance without causing a compensatory increase in heart rate [17][18][19][20] or changing baroreceptor activity.…”

Section: Angiotensin-converting Enzyme Inhibitorsmentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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“…22 However, with chronic ACE inhibitor treatment, the relationship between BP reduction and pre-treatment plasma renin levels diminishes. 23,24 Thus race does not appear to alter this relationship. However, our data regarding renin profiling needs to be viewed carefully since we did not use any provocative or suppressive manoeuvers to alter renin responses.…”

Section: Discussionmentioning

confidence: 90%

Renin status does not predict the anti-hypertensive response to angiotensin-converting enzyme inhibition in African–Americans

Saunders

1998

J Hum Hypertens

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The angiotensin-converting enzyme (ACE) inhibitor trandolapril, a non-sulfhydryl prodrug which is hydrolysed into trandolaprilat, was studied in 322 hypertensives of African-American descent using a doubleblind, randomised, placebo-controlled, parallel study design. Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day trandolapril, an analysis of drug effect on trough blood pressure (BP) stratified by age, gender, weight, pre-treatment plasma renin activity, and trandolaprilat concentration was performed. Two mg was the lowest effective trandolapril dose, whereas doses above 4 mg did not significantly reduce

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Prediction of sustained antihypertensive efficacy of chronic captopril therapy: Relationships to immediate blood pressure response and control plasma renin activity

Cited by 33 publications

References 16 publications

Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.

Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart.

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

Renin status does not predict the anti-hypertensive response to angiotensin-converting enzyme inhibition in African–Americans

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