Repeated Administration of the Converting Enzyme Inhibitor Cilazapril to Normal Volunteers

Nussberger, Juerg; D'amore, T. Fasanella; Porchet, M; Waeber, B; Brunner, D. B.; Brunner, Hans R.; Kler, Lata; Brown, A. N.; Francis, Robert J.

doi:10.1097/00005344-198701000-00007

Cited by 123 publications

(66 citation statements)

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“…Plasma renin activity [15,16], plasma aldosterone [17] and atrial natriuretic peptide [18] were determined as described previously. BNP was measured by immunoassay (Biosite Triage BNP test, Biosite, Morges, Switzerland).…”

Section: Analytical Methods and Calculation Of Renal Variablesmentioning

confidence: 99%

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

et al. 2010

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Aims/hypothesis Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. Methods In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Results Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the bloodpressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Conclusions/interpretation Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.

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Section: Analytical Methods and Calculation Of Renal Variablesmentioning

confidence: 99%

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

et al. 2010

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“…For measurement of biomarkers of RAAS activity, two 6 ml samples of blood were taken by venepuncture and plasma extracted into EDTA tubes. Biomarkers measured were PRA (measured by the trapping of generated angiotensin I by high-affinity antibodies and by subsequent radioimmunoassay 20 ), plasma renin concentration (PRC; IRMA kit; Cisbio, Gif sur Yvette, France), prorenin (measured as the difference between measured PRC and total renin measured by Cisbio IRMA following 'activation' of all prorenin by incubation of plasma for 48 h at 4 1C in the presence of 10 000 nmol l À1 aliskiren) and aldosterone (solid-phase radioimmunoassay; Diagnostic Products Corporation, Los Angeles, CA, USA). RAAS biomarkers were measured at the Erasmus Medical Center, Rotterdam, the Netherlands.…”

Section: Biomarker Assessmentsmentioning

confidence: 99%

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Krone

Hanefeld

Hf³

et al. 2010

J Hum Hypertens

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Metabolic syndrome, a cluster of risk factors that increase the risk of cardiovascular morbidity and mortality, is common in patients with hypertension. Chronic renin-angiotensin-aldosterone system (RAAS) activation, shown by elevated plasma renin activity (PRA), is implicated in many of the features of metabolic syndrome. The direct renin inhibitor aliskiren may be of benefit in this patient group as aliskiren targets the RAAS at the rate-limiting step. In this double-blind study, 141 patients with hypertension (mean baseline BP 155/93 mm Hg) and metabolic syndrome (modified National Cholesterol Education Program ATP III criteria) were randomized to aliskiren 300 mg or irbesartan 300 mg once daily. Patients treated with aliskiren 300 mg had their mean sitting blood pressure (BP) lowered by 13.8/ 7.1 mm Hg after 12 weeks, significantly greater (Pp0.001) than the 5.8/2.8 mm Hg reduction observed in patients treated with irbesartan 300 mg. A significantly greater proportion of patients treated with aliskiren achieved BP control to o135/85 mm Hg (29.2 vs 16.7% with irbesartan; P ¼ 0.019). Aliskiren treatment led to a 60% decrease in PRA from baseline, whereas irbesartan increased PRA by 99% (both Po0.001). Aliskiren and irbesartan had similar effects on glucose and lipid profiles and on a panel of biomarkers of inflammation and cardiovascular risk. Both aliskiren and irbesartan were well tolerated. Collectively, these results suggest that aliskiren 300 mg may offer treatment benefits compared with irbesartan 300 mg for BP reduction in patients with hypertension and metabolic syndrome.

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“…PRA was measured by the trapping of generated Ang I by antibodies and by subsequent radioimmunoassay. 20 Aliskiren was measured in 2.5 L of plasma by direct radioimmunoassay with a limit of quantification of 0.15 ng/mL and with intra-assay and inter-assay coefficients of variation Ͻ15%. 14 …”

Section: Assessment Of Pra and Aliskiren Levelsmentioning

confidence: 99%

Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker

et al. 2007

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Abstract-Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (nϭ23), ramipril (nϭ21), or irbesartan (nϭ23). In the diuretic combination study, . Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (PϽ0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased ( Key Words: aliskiren Ⅲ ambulatory blood pressure measurement Ⅲ combination therapy Ⅲ hypertension Ⅲ plasma renin activity Ⅲ renin inhibitor Ⅲ renin-angiotensin-aldosterone system A ctivation of the renin-angiotensin (Ang)-aldosterone system (RAAS) plays an important role in the development of hypertension and end-organ damage. 1 Indeed, pretreatment plasma renin activity (PRA) has been shown to be a risk factor for myocardial infarction in hypertensive patients. 2,3 RAAS suppression is, therefore, an important goal of antihypertensive therapy, and RAAS inhibitors, such as Ang-converting enzyme (ACE) inhibitors and Ang receptor blockers (ARBs), have proven to be highly successful treatments for hypertension, heart failure, and related cardiovascular disorders. 4 However, optimized RAAS suppression is difficult to achieve with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate compen-

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Repeated Administration of the Converting Enzyme Inhibitor Cilazapril to Normal Volunteers

Cited by 123 publications

References 0 publications

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker

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