β-Blockade in Hypertension and Congestive Heart Failure

Ambrosioni, Ettore; Bacchelli, Stefano; Esposti, Daniela Degli; Borghi, Claudio

doi:10.1097/00005344-200112003-00005

Cited by 13 publications

(8 citation statements)

References 64 publications

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“…Despite recent advances in the treatment and the primary prevention of heart failure (1,115,168,178), the long-term prognosis for patients who present with this diagnosis remains dismal and the economic burden to the health care system is huge (47,133). In this perspective, a consideration of the role of the brain may be critically important in the development of effective therapeutic strategies.…”

Section: Translational Aspectsmentioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

109

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Heart failure and the brain: new perspectives. Am J Physiol Regul Integr Comp Physiol 284: R259-R276, 2003; 10.1152/ajpregu.00317.2002.-Despite recent therapeutic advances, the prognosis for patients with heart failure remains dismal. Unchecked neurohumoral excitation is a critical element in the progressive clinical deterioration associated with the heart failure syndrome, and its peripheral manifestations have become the principal targets for intervention. The link between peripheral systems activated in heart failure and the central nervous system as a source of neurohumoral drive has therefore come under close scrutiny. In this context, the forebrain and particularly the paraventricular nucleus of the hypothalamus have emerged as sites that sense humoral signals generated peripherally in response to the stresses of heart failure and contribute to the altered volume regulation and augmented sympathetic drive that characterize the heart failure syndrome. This brief review summarizes recent studies from our laboratory supporting the concept that the forebrain plays a critical role in the pathogenesis of ischemiainduced heart failure and suggesting that the forebrain contribution must be considered in designing therapeutic strategies. Forebrain signaling by neuroactive products of the renin-angiotensin system and the immune system are emphasized.angiotensin; aldosterone; cytokines; tumor necrosis factor; immune system; renin; vasopressin; sympathetic; extracellular fluid volume; baroreflex THE IMPORTANCE OF AUTONOMIC dysfunction to the progression of heart failure is firmly established (55,113,120,152). The most effective treatments for heart failure specifically target the peripheral manifestations of neurohumoral activation (86,113). Yet the understanding of the mechanisms leading to neurohumoral excitation in heart failure is still quite limited.Over the last several decades, substantial evidence has been amassed to support the concept that peripheral afferent systems innervating the heart and vascular tree are altered in heart failure. Dysfunction has been described in all components of the reflexes mediated by these cardiovascular afferent systems-the afferent fibers themselves, the central processing of the afferent signals, the efferent innervation of the end organs, and the end organs themselves. In general, the influence of low-and high-pressure baroreceptors (40,42,191) that normally restrain sympathetic drive and vasopressin release is diminished, whereas the excitatory influences of arterial chemoreceptors (161) and cardiac sympathetic afferent fibers (100) are enhanced.Central nervous system (CNS) neurons affecting cardiovascular regulation respond to humoral as well neural signals. Blood-borne neuroactive peptides, too large to readily cross the blood-brain barrier, may influence the brain by activating sensory neurons at specific sites in hindbrain and forebrain that lack a blood-brain barrier (15,18) or by inducing the release of mediators that do penetrate the barrier (135). These neuroactive s...

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Section: Translational Aspectsmentioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

109

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“…Inactivation of NO signaling by reactive oxygen species may be one of the major mechanisms whereby oxidative stress promotes hypertrophy (10). Moreover, treatments that have been shown to attenuate cardiac hypertrophy in heart failure (angiotensin converting enzyme inhibitors, beta-blockers, and hydralazine/nitrates), increase NO bioavailability and promote NO signaling (1,33). Our findings identify specific transcriptional targets of NO signaling in cardiac hypertrophy, some of which may be targets for pharmacological intervention.…”

Section: Fig 3 Cluster Analysis Of Gene Expression In Nosmentioning

confidence: 77%

“…Next, we required at least a 1. 1 and identified the corresponding probe sets on the MG-U74A array. In effect, this collection of probe sets defines a hypertrophy-specific subset.…”

Section: And Nos1mentioning

confidence: 99%

Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy

Cappola

Cope

Cernetich

et al. 2003

Physiological Genomics

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Decreased nitric oxide synthase (NOS) activity induces left ventricular hypertrophy (LVH), but the transcriptional pathways mediating this effect are unknown. We hypothesized that specific NOS isoform deletion (NOS3 or NOS1) would activate different transcriptional programs in LVH. We analyzed cardiac expression profiles (Affymetrix MG-U74A) from NOS−/− mice using robust multi-array average (RMA). Of 12,422 genes analyzed, 47 genes were differentially expressed in NOS3−/− and 67 in NOS1−/− hearts compared with wild type (WT). Only 16 showed similar changes in both NOS−/− strains, most notably decreased heat-shock proteins (HSP10, 40, 70, 86, 105). Hypertrophied NOS1−/− hearts had unique features, including decreased myocyte-enriched calcineurin interacting protein and paradoxical downregulation of fetal isoforms (α-skeletal actin and brain natriuretic peptide). Cluster analyses demonstrated that NOS1 deletion caused more pronounced changes in the myocardial transcriptome than did NOS3 deletion, despite similar cardiac phenotypes. These findings suggest that the transcriptional basis for LVH varies depending on the inciting biochemical stimulus. In addition, NOS isoforms appear to play distinct roles in modulating cardiac structure.

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“…Compared with angiotensin-converting-enzyme inhibitors (ACE inhibitors), Nebivolol showed a greater percentage of patients that reached the target values and was comparable to the angiotensin 2 receptor antagonists (AT2) and calcium channel blockers [43]. Maximum antihypertensive action is observed between week 2 and 8 of treatment, which is intermediate between the ACE inhibitors (slower) and amlodipine (faster) [44].…”

Section: Beta-blockers In High Blood Pressure (Hbp)mentioning

confidence: 99%

Nebivolol: Does the key lie in β3 agonism?

Arazi¹,

Gonzalez²

2017

Vascul Dis Ther

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Beta-blockers are drugs indicated in the treatment of multiple cardiovascular pathologies. The review highlights the mechanisms of action of Nebivolol and its particular potential effect on β3 receptors that increases nitric oxide that may mark very significant differences, which are traduced to benefits in clinical results.Nebivolol has an special place in the treatment of adrenergic hypertension associated with tachycardia and emotional stress, more frequently in young individuals, and may be considered adequate even in patients with glucose and lipid metabolism disorders due to its pleiotropic effect.In patients with heart failure, Nebivolol showed effectiveness and safety in patients over 75 years old.Nebivolol showed a reduction of cardiomyocyte apoptosis and improvement of contractile function through a mechanism related to β3 receptor agonism after an acute coronary syndrome.Because of all these actions Nebivolol should be considered not only a third-generation Beta-blocker.

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β-Blockade in Hypertension and Congestive Heart Failure

Cited by 13 publications

References 64 publications

Heart failure and the brain: new perspectives

Heart failure and the brain: new perspectives

Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy

Nebivolol: Does the key lie in β3 agonism?

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