H. R. Brunner

Bio: H. R. Brunner is an academic researcher from Boston Medical Center. The author has contributed to research in topics: Blood pressure & Angiotensin-converting enzyme. The author has an hindex of 34, co-authored 139 publications receiving 3654 citations.

Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.

Abstract: The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.

True versus immunoreactive angiotensin II in human plasma.

Abstract: To measure specifically angiotensin-(1-8)octapeptide, peptides were extracted from 2 ml of plasma by reversible adsorption to bonded-phase silica. The angiotensin-(1-8)octapeptide was then isolated by isocratic reversed-phase high-performance liquid chromatography and quantified by radioimmunoassay. The extraction recovery of 125I-angiotensin II added to 2 ml of plasma was 99 +/- 2% (mean +/- SD). The overall recovery of 5, 10, and 20 fmol unlabeled angiotensin II added to 1 ml of plasma was 80 +/- 10%. The coefficient of variation for within-assay precision was 0.06 and for between-assay precision 0.13. The detection limit was 0.4 fmol/ml. Buffer and plasma blanks were below the detection limit. Normal subjects on a free diet in supine position averaged 4.2 +/- 1.7 fmol/ml angiotensin-(1-8)octapeptide. Furosemide (40 mg p.o.) and standing increased these values to 22 +/- 7.6 fmol/ml. In four volunteers, immunoreactive "angiotensin II" (more or less angiotensin-like material) was measured serially before and after converting-enzyme inhibition (Hoe 498) with conventional Dowex extraction. At peak inhibition, plasma immunoreactive "angiotensin II" levels decreased by only 44%. In contrast, angiotensin-(1-8)-octapeptide isolated by high-performance liquid chromatography completely disappeared. In hypertensive patients receiving long-term treatment with enalapril, plasma levels of angiotensin-(1-8)octapeptide fell from 2.7 +/- 0.9 to 0.9 +/- 0.3 fmol/ml (mean +/- SEM) 2 hours after the morning dose, whereas levels of immunoreactive "angiotensin II" were not significantly changed. We found that this sensitive method specifically measured angiotensin-(1-8)octapeptide and demonstrated that true angiotensin II virtually disappears during converting-enzyme inhibition.

Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition.

Abstract: Summary The new ACE inhibitor trandolapril was administered to normal volunteers at daily doses of 0.5, 2, and 8 mg for 10 days. Twenty-one volunteers, aged 21–30 years, were included in the study. To randomly selected groups of seven subjects, each dose was administered in a single-blind fashion. None of the doses induced a consistent fall in blood pressure. Angiotensin-converting enzyme activity (ACE) was measured in vitro using three different synthetic substrates (i.e., Hip-Gly-Gly, ZPhe-His-Leu, or angiotensin I). Although the degree of ACE inhibition assessed with the three methods varied widely, all methods clearly indicated dose-dependent ACE inhibition. These in vitro results were confirmed by measuring ACE inhibition in vivo using the ratio of plasma angiotensin II (ANG II) to blood angiotensin I (ANG I). The dose-dependent ACE inhibition was paralleled by a dose-dependent rise in active renin and blood angiotensin I levels, most evident on day 10. In contrast, plasma ANG II levels on day 10 were not different whether the volunteers received 0.5 or 8 mg trandolapril. Thus, whereas increasing doses of this new ACE inhibitor progressively enhanced the blockade of ACE activity, this was not reflected by additional reductions of plasma ANG II levels. The progressive enhancement of ACE inhibition seemed to be offset by the accentuation of the compensatory rise in renin and ANG I, which was still partially converted to ANG II. These data strongly suggest that, particularly with long-term administration, in-creasing the dose of an ACE inhibitor may further inhibit ACE activity but does not necessarily result in progressively lower levels of circulating ANG II.

Repeated Administration of the Converting Enzyme Inhibitor Cilazapril to Normal Volunteers

Abstract: Summary: Cilazapril 1.25 and 5.0 mg p.o. q.d. was administered in double-blind fashion to two groups of six normal volunteers on 8 consecutive days. Blood pressure, heart rate, and plasma converting enzyme activity were measured each day prior to drug administration and up to 72 h after the last dose. Plasma renin activity, blood angiotensin I, plasma angiotensin II, and aldosterone as well as plasma cilazaprilat levels were determined on the first and the last day of active treatment at times 0, 4, and 24 h. The drug was very well tolerated by all volunteers. At 4 h postdrug, plasma converting enzyme activity was reduced in dose-dependent fashion on the first and the eighth day; plasma cilazaprilat levels were also clearly dose dependent. Nevertheless, 24 h postdrug cilazaprilat levels were similar on the first and last day of drug administration, and plasma converting enzyme activity was also stable throughout the 8 days. The various components of the renin-angiotensin system responded in the usual fashion. These results provide strong evidence that cilazapril is a very potent and highly effective converting enzyme inhibitor. Doses well below 5 mg/day will probably suffice for therapeutic efficacy. These data also confirm the hypothesis formulated in the preceding article, i.e., that there is no accumulation of the drug with repeated administration despite its long pharmacological half-life (t½).

Specific measurement of angiotensin metabolites and in vitro generated angiotensin II in plasma.

Abstract: Combining high-performance liquid chromatography with radioimmunoassay enabled the precise measurement of different angiotensins and their metabolites in plasma. Peptides were extracted from 2 ml of plasma by reversible adsorption to phenylsilyl-silica, separated by isocratic high-performance liquid chromatography, and quantitated by radioimmunoassay using a sensitive but suitably cross-reacting angiotensin II antiserum. For the C-terminal angiotensin II metabolites (2-8)heptapeptide, (3-8)hexapeptide, and (4-8)pentapeptide, overall recoveries of 10 fmol peptide added to 1 ml of plasma were (mean +/- SD), 74 +/- 6, 68 +/- 8, and 67 +/- 11%, respectively. The detection limit for these peptides in plasma was 0.2 fmol/ml. Blanks were below the detection limits. In eight seated normal subjects treated for 4 days with enalapril, 20 mg p.o., q.d., angiotensin II metabolites tended to decrease during the 4 postdrug hours. However, their cumulated concentration in relation to octapeptide increased from 54 to 163% on Day 1 and from 62 to 103% on Day 4. After 4 hours of converting enzyme inhibition with enalapril there was still a close correlation between plasma renin activity and angiotensin-(1-8)octapeptide level (r = 0.83, p less than 0.05) and between blood angiotensin I and angiotensin-(1-8)octapeptide levels (r = 0.86, p less than 0.01). Adding angiotensin I in vitro raised the angiotensin-(1-8)octapeptide levels after incubation at 4 degrees C for 4 hours. Thus, immunoreactive "angiotensin II" does not disappear after converting enzyme inhibition largely because of the cumulated contribution of cross-reacting metabolites and partly because of in vitro generation of true angiotensin II.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

Abstract: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 1. Epidemiological data on hypertension and BP control in Europe. 2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 7. Hypertension in young people. 8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients. 10. Liberal approach to initial monotherapy, without any all-ranking purpose. 11. Revised schema for priorital two-drug combinations. 12. New therapeutic algorithms for achieving target BP. 13. Extended section on therapeutic strategies in special conditions. 14. Revised recommendations on treatment of hypertension in the elderly. 15. Drug treatment of octogenarians. 16. Special attention to resistant hypertension and new treatment approaches. 17. Increased attention to OD-guided therapy. 18. New approaches to chronic management of hypertensive disease

European guidelines on cardiovascular disease prevention in clinical practice (version 2012) : the fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).

Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …