Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27

Montgomery, Hugh; Kiernan, L; Whitworth, Caroline; Fleming, Stewart; Unger, Thomas; Gohlke, Peter; Mullins, John J.; McEwan, Jean R.

doi:10.1097/00004872-199816050-00011

Cited by 59 publications

(41 citation statements)

References 51 publications

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“…Some aspects of the pathophysiology of hypertensive crises have been clarified (for example, amplification in renin system activity) and some clinical conditions are associated with hypertensive crises through well-defined pathophysiological mechanisms (for example, in pheochromocytoma, cerebral ischaemia or renal artery stenosis). [23][24][25] However, the factors leading to a severe and rapid BP rise are poorly understood in the majority of patients with hypertensive crisis. 3,26,27 If BP regulation follows the laws of a deterministic chaotic process, hypertensive crisis might also be a dissipation of BP regulation itself.…”

Section: Discussionmentioning

confidence: 99%

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Schoenenberger

Erné²,

Ammann

et al. 2007

J Hum Hypertens

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Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fiftyseven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (Po0.01), average of systolic BP (P ¼ 0.02) and average of diastolic BP (P ¼ 0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; Po0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P ¼ 0.01) and average of diastolic BP (Po0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

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Section: Discussionmentioning

confidence: 99%

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Schoenenberger

Erné²,

Ammann

et al. 2007

J Hum Hypertens

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“…1,2 Recent studies have reinforced the notion that angiotensin (Ang) II plays an important role in the development of malignant hypertension. Using different transgenic rat models characterized by overexpression of genes of the renin-angiotensin system, Montgomery et al 3 and Mervaala et al 4,5 showed that blockade of Ang II prevented the development of malignant hypertension in these models. These authors provided some evidence that inhibition of converting enzyme 3 and renin 4 were effective even if blood pressure was not lowered.…”

mentioning

confidence: 99%

“…Using different transgenic rat models characterized by overexpression of genes of the renin-angiotensin system, Montgomery et al 3 and Mervaala et al 4,5 showed that blockade of Ang II prevented the development of malignant hypertension in these models. These authors provided some evidence that inhibition of converting enzyme 3 and renin 4 were effective even if blood pressure was not lowered. Blood pressure, however, was assessed only by the tail-cuff measurements in anesthetized animals.…”

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confidence: 99%

Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension

Hilgers¹,

Hartner²,

Porst³

et al. 2001

Circulation

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Background-Angiotensin II is elevated in malignant hypertension. We tested the hypothesis that angiotensin II type 1 receptor blockade can prevent the development of malignant hypertension even in the absence of a blood pressure-lowering effect. Methods and Results-Two-kidney, 1-clip rats were followed up for 28 days; blood pressure was measured by tail-cuff plethysmography and intra-arterially. After a 2-week run-in phase, rats received valsartan at a dose of 0.3 (nϭ14) or 3 (nϭ12) mg · kg Ϫ1 · d Ϫ1 or solvent (nϭ27). Only the higher dose of valsartan, but not the lower dose, decreased blood pressure. Both doses of valsartan prevented the development of lethal malignant hypertension. Twenty of 27 solvent-treated renovascular hypertensive rats died, but only 3 of 14 rats treated with the low dose and 1 of 12 rats treated with the high dose of valsartan died. Histological signs of malignant nephrosclerosis were found in all rats examined that had died throughout the study and in 6 of 7 surviving solvent-treated renovascular hypertensive animals. Increased expression of monocyte chemoattractant protein-1 and prominent interstitial influx of macrophages occurred in the nonclipped kidneys exposed to high pressure in solvent-treated rats. These alterations were prevented by valsartan at both doses, irrespective of blood pressure effects. Conclusions-Angiotensin II type 1 receptor blockade by valsartan prevents lethal malignant hypertension independently of blood pressure. The results suggest that reduction of angiotensin-induced inflammation in the kidney may contribute to the protective effects of valsartan.

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“…19 In spite of this, cardiac remodeling processes were found to be quite different. The mRen2 activation in IHR led to inward concentric myocardial remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 In contrast, in TGR, the mRen2 gene is expressed in many organs including the heart 22 and local rather than systemic production of Ang II has been held responsible for the phenotype. 19,29 Recently, Vanourkova et al have shown that feeding IHR 0.3% I3C for a period of 10 days leads to a cardiac hypertrophic response that could be prevented by co-administration of the AT 1 receptor blocker valsartan but not by triple therapy with reserpine, hydralazine and hydrochlorothiazide. Remarkably, while both treatments were equipotent in reducing BP, tissue Ang II levels and cardiac remodeling were blunted during AT 1 receptor blockade but not triple therapy.…”

Section: Several Factors May Have Contributed To the Characteristic Cmentioning

confidence: 99%

Cardiac remodeling during and after renin–angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

Heijnen

Pelkmans

Danser

et al. 2013

J Renin Angiotensin Aldosterone Syst

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This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle. Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR.

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Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27

Cited by 59 publications

References 51 publications

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension

Cardiac remodeling during and after renin–angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

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