Comparison of the Effects of Captopril and Nicardipine on Insulin Sensitivity and Thrombotic Profile in Patients With Hypertension and Android Obesity

Raccah, D.; Pettenuzzo-Mollo, M; Provendier, O; Boucher, Luc; Ja, Cozic; Gorlier, R; Huin, P; Sicard, Jérôme; Vague, P

doi:10.1093/ajh/7.8.731

Cited by 14 publications

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“…8,20,21 However, mean BMI at baseline in the present study (34.4 kg/m 2 ) was higher than in previous studies and suggests that close to half of the patients enrolled had BMI Ն35 kg/m 2 , that is, obesity grade 2 (BMI: 35 to 39.9 kg/m 2 ) or grade 3 (BMI: Ն40 kg/m 2 ). Nevertheless, BP control rates with aliskiren/ HCTZ compare favorably with the control rates of 34% and 38% observed with valsartan and the ␤-blocker atenolol, respectively (with addition of 12.5 to 25 mg of HCTZ as LSM indicates least-squares mean.…”

Section: Discussioncontrasting

confidence: 72%

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

et al. 2007

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Abstract-Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index Ն30 kg/m 2 ; mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2-to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (PϽ0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/ HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/ HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment. Key Words: direct renin inhibitor Ⅲ Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 Ⅲ obesity Ⅲ renin-angiotensin system Ⅲ thiazide diuretic T he proportion of hypertensive patients who are obese has increased steadily in recent years. Given that 75% of obese patients have hypertension, but Ͻ20% have their blood pressure (BP) controlled to Ͻ140/90 mm Hg, 1 there is a clear need for new antihypertensive treatment options for this patient group. Yet, current guidelines do not provide specific guidance for the treatment of this patient population, 2 and data from larger clinical trials addressing the issue are lacking. This state of affairs is surprising, because the underlying pathophysiology differs between lean and obese patients with arterial hypertension. In particular, obesityassociated hypertension involves activation of the renin system, 3,4 volume expansion, and increased cardiac output 5-7 rather than systemic vasoconstriction. Combination of a low dose of a thiazide diuretic with a renin system inhibitor may, therefore, be a suitable treatment approach. 8 Aliskiren is the first in a new class of direct renin inhibitors. 9,10 Combination treatment with a renin system inhibitor is a theoretically attracti...

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Section: Discussioncontrasting

confidence: 72%

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

et al. 2007

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“…The beneficial effects of inhibition of the RAS in the progression of diabetic nephropathy, hypertension and cardiovascular diseases have been reported in many clinical trials (Shieh et al 1992, Torlone et al 1993, Raccah et al 1994, Mohanran & Toto 2003. Ang II has been found to attenuate or inhibit insulin signalling in vascular smooth muscle cells (Vellosa et al 1996, Folli et al 1997, Fukuda et al 2001, implicating a role for the RAS in regulating the actions of insulin.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Hsieh¹,

Fustier²,

Wei³

et al. 2004

Journal of Endocrinology

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We reported previously that insulin inhibits the stimulatory effect of high glucose on the expression of angiotensinogen (ANG) gene in both rat immortalized renal proximal tubular cells (IRPTCs) and non-diabetic rat renal proximal tubular cells (RPTCs), but has no effect in diabetic rat RPTCs. In the present study we investigated whether hyperglycaemia-induced resistance to the insulininduced inhibition of expression of the ANG gene is mediated via the generation of reactive oxygen species (ROS) in RPTCs. Rat IRPTCs were cultured for 2 weeks in high-glucose (25 mM) or normal-glucose (5 mM) medium plus angiotensin II (Ang II) with or without a superoxide scavenger (tiron), or inhibitors of: NADPH oxidase (diphenylene iodinium, DPI), Ang II type 1 and 2 receptors (losartan and PD123319), angiotensinconverting enzyme (perindopril), protein kinase C (GF 109203X), or glutamine:fructose-6-phosphate aminotransferase (azaserine). Cellular generation of ROS, and ANG and renin mRNA levels were assessed by lucigenin assay and specific reverse transcriptase-PCR respectively. Phosphorylation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) was evaluated by western blotting. Prolonged exposure of IRPTCs to high concentrations of glucose or Ang II evoked generation of ROS and resistance to the insulin-induced inhibition of expression of the ANG gene and of p44/42 MAPK phosphorylation. Co-incubation of IRPTCs with tiron, DPI, losartan, PD123319, perindopril, GF 109203X or azaserine prevented ROS generation, restoring the inhibitory action of insulin on ANG gene expression and on p44/42 MAPK phosphorylation. In conclusion, our studies demonstrate that blockade of both ROS generation and activation of the intrarenal renin-angiotensin system improves the inhibitory action of insulin on ANG gene expression in IRPTCs in conditions of high glucose.

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“…9,10,[34][35][36] Several experimental studies have shown that PAI-1 activity is stimulated by angiotensin II, or associated with ACE gene polymorphism, 37 although this latter association has been questioned by others. 38 Thus, antihypertensive drugs acting within the renin-angiotensin system should also exert effects within the fibrinolytic system.…”

Section: Discussionmentioning

confidence: 99%

Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME Study

et al. 2000

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Aims: To assess the association of hypertensive status and antihypertensive drug treatment with lipid and haemostatic levels in middle-aged men. Methods and results: Hypertensive status, antihypertensive drug treatment, total and high-density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B, lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years living in France (n ‫؍‬ 7050) and Northern Ireland (n ‫؍‬ 2374). After adjustment for age, body mass index, smoking status, educational level, country, alcohol drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I activity than normotensive subjects. On univariate analysis, diuretics decreased total and HDL-cholesterol and apoproteins A-I and B; those differences remained after multivariate adjustment. Treatment with beta-blockers decreased total and HDL-cholesterol, apoprotein A-I and LpA-I, and

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Comparison of the Effects of Captopril and Nicardipine on Insulin Sensitivity and Thrombotic Profile in Patients With Hypertension and Android Obesity

Cited by 14 publications

References 0 publications

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

Direct Renin Inhibition With Aliskiren in Obese Patients With Arterial Hypertension

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME Study

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