Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combined therapy with lozartan and metoprolol in patients with chronic cardiac insufficiency has a consistent effect on the levels of epinephrine, angoitensin II, vasopressin, atrial naturiuretic factor, insulin, endothelline, thromboxane B2, guanosine monophosphate, 6-keto prostaglandin F1 alpha, and bradikinin. As to norepinephrine, there has been noted an inconsistent therapeutic effect. It is suggested that the time-related course of a long-term therapy might be associated with a formation of the aldosterone "escape" phenomenon.
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PMID:[Stability of neurohumoral effects of losartan combined with metoprolol in chronic cardiac low output]. 1258 23

Erectile dysfunction (ED) often is caused by endothelial dysfunction and may be a sign that a patient has vascular disease elsewhere in the body. Risk factors for coronary artery disease such as lipid abnormalities, smoking, diabetes, and hypertension also are risk factors for ED. Oral therapy for ED, such as sildenafil, inhibits phosphodiesterase-5 (PDE-5) and the breakdown of cyclic guanosine monophosphate. PDE-5 inhibitors have been shown to be safe and effective for the therapy for ED, but remain contraindicated in patients receiving organic nitrates. These agents are mild vasodilators and are being investigated for their treatment potential for patients with pulmonary hypertension, heart failure, and endothelial dysfunction.
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PMID:Erectile dysfunction in the cardiac patient. 1462

The natriuretic peptides, including human B-type natriuretic peptide (BNP), have been implicated in the regulation of cardiac remodeling. Because transforming growth factor-beta (TGF-beta) is associated with profibrotic processes in heart failure, we tested whether BNP could inhibit TGF-beta-induced effects on primary human cardiac fibroblasts. BNP inhibited TGF-beta-induced cell proliferation as well as the production of collagen 1 and fibronectin proteins as measured by Western blot analysis. cDNA microarray analysis was performed on RNA from cardiac fibroblasts incubated in the presence or absence of TGF-beta and BNP for 24 and 48 hours. TGF-beta, but not BNP, treatment resulted in a significant change in the RNA profile. BNP treatment resulted in a remarkable reduction in TGF-beta effects; 88% and 85% of all TGF-beta-regulated mRNAs were affected at 24 and 48 hours, respectively. BNP opposed TGF-beta-regulated genes related to fibrosis (collagen 1, fibronectin, CTGF, PAI-1, and TIMP3), myofibroblast conversion (alpha-smooth muscle actin 2 and nonmuscle myosin heavy chain), proliferation (PDGFA, IGF1, FGF18, and IGFBP10), and inflammation (COX2, IL6, TNFalpha-induced protein 6, and TNF superfamily, member 4). Lastly, BNP stimulated the extracellular signal-related kinase pathway via cyclic guanosine monophosphate-dependent protein kinase signaling, and two mitogen-activated protein kinase kinase inhibitors, U0126 and PD98059, reversed BNP inhibition of TGF-beta-induced collagen-1 expression. These findings demonstrate that BNP has a direct effect on cardiac fibroblasts to inhibit fibrotic responses via extracellular signal-related kinase signaling, suggesting that BNP functions as an antifibrotic factor in the heart to prevent cardiac remodeling in pathological conditions.
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PMID:B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. 1472 74

In 15 patients with chronic heart failure of ischemic origin who were not previously treated with angiotensin-converting enzyme inhibitors, platelets exhibited hyperaggregability and impaired responsiveness to the antiaggregatory and cyclic guanosine monophosphate-stimulatory effects of nitric oxide donor sodium nitroprusside compared with normal subjects; this was paralleled by increased blood levels of superoxide radicals. Treatment with perindopril for 4 days significantly improved platelet responses to sodium nitroprusside; there was also a trend toward a decrease in superoxide radical levels.
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PMID:Effect of perindopril on platelet nitric oxide resistance in patients with chronic heart failure secondary to ischemic left ventricular dysfunction. 1516 36

The autonomic nervous system (ANS), a complex and self-organized entity, plays a crucial role in cardiovascular regulation. In this review, the authors describe some concepts of anatomo-physiology and cellular/molecular biology of the ANS and of its two major components, the parasympathetic and sympathetic system, both in the normal individual and in the patient with heart failure. Adrenergic and cholinergic neurotransmission, neurotransmitters, adrenergic and cholinergic receptors and intracellular signal transduction are discussed. Some aspects of sympathetic-parasympathetic interaction at the cellular level are described as well as the opposite role of two cyclic nucleotides, cyclic adenosine and guanosine monophosphate. Major emphasis is placed on the beta-adrenergic system, the combination of the beta receptor, G protein complex and adenylyl cyclase. The activation of neurohumoral compensatory mechanisms in heart failure is discussed as well as the increasingly recognized importance of sympathetic overactivation and parasympathetic tonus reducting in this setting. Cellular mechanisms of adrenergic stimulation in heart failure and its consequences are presented, with special focus on down-regulation of beta-1 adrenergic receptors; the authors analyze the steps of phosphorlation and oncoupling, sequestration, internalization and lysosomal degradation, the main result of which is reduced response to catecholamines.
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PMID:[Autonomic nervous system in heart failure]. 1522 50

The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Pulmonary arterial hypertension (PAH) and heart failure (HF) are characterized by pulmonary arterial vasoconstriction that is thought to be caused by relative deficiencies of vasodilators such as NO and exaggerated production of vasoconstrictors such as endothelin. PDE5 is abundant in the pulmonary vasculature where it catabolizes cGMP, the second messenger of NO. Inhibition of PDE5 has been shown to lower pulmonary vascular resistance in PAH and HF by augmenting local cGMP. This review outlines the therapeutic potential of PDE5 inhibition for the treatment of PAH and HF.
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PMID:Type 5 phosphodiesterase inhibition in heart failure and pulmonary hypertension. 1603 43

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.
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PMID:An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans. 1612 23

Patients with heart failure (HF) due to left ventricular (LV) systolic dysfunction have abnormal endothelium-dependent, nitric oxide-cyclic guanosine monophosphate-mediated vasodilation in the pulmonary and skeletal muscle vasculature. Therefore, inhibition of type 5 phosphodiesterase (PDE5), the principle enzyme responsible for cyclic guanosine monophosphate catabolism in the lungs and skeletal muscle, has been targeted in an effort to counteract vasoconstriction that contributes to increased right and LV afterload in HF. The efficacy of PDE5 inhibition in the treatment of pulmonary arterial hypertension has led to the investigation of its potential utility in the treatment of HF patients with secondary pulmonary hypertension. Moreover, recent preclinical studies suggest direct myocardial effects of PDE5 inhibition that may counteract beta-adrenergic, hypertrophic, and pro-apoptotic signaling, three critical pathways in the development of LV dysfunction. This review outlines both the underlying rationale and the results of initial studies of the therapeutic effects of PDE5 inhibition in HF.
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PMID:The emerging role for type 5 phosphodiesterase inhibition in heart failure. 1691 4

Type V phosphodiesterase (PDE V) metabolizes cyclic guanosine monophosphate (cGMP) and is abundant in the kidney and vasculature and was found recently in the heart. Sildenafil is a PDE V inhibitor that is used clinically for erectile dysfunction. Brain natriuretic peptide (BNP) is a cardiac peptide with vasodilating, lusitropic, and natriuretic properties that are mediated via cGMP. It was hypothesized that chronic inhibition of PDE V (PDE VI) will enhance the renal actions of exogenous BNP by potentiating the renal cGMP. The cardiorenal and humoral function was determined at baseline in two groups of dogs with pacing-induced overt chronic heart failure (CHF; 240 bpm for 10 d): Group 1 (n = 6) received Sildenafil 50 mg orally three times daily during the 10 d of pacing, and group 2 (n = 5) received no PDE V inhibitor. The response to acute subcutaneous BNP (5 microg/kg) administration also was compared in both groups on day 11. The GFR was assessed by inulin clearance (P < 0.05). There was no improvement of renal function in group 1 after 10 d of PDE VI as compared with group 2, despite having higher cardiac output (P < 0.05). Group 1 had significantly higher plasma (44 +/- 2 versus 21 +/- 3 pmol/ml; P < 0.05) and urinary cGMP (4219 +/- 900 versus 1954 +/- 300 pmol/min; P < 0.05) as compared with group 2. With acute subcutaneous BNP administration, group 1 had a natriuretic and diuretic response that was associated with an increase in GFR (30 +/- 6 to 45 +/- 6 ml/min; P < 0.05) and that was not observed in group 2 (25 +/- 6 to 29 +/- 4 ml/min). Plasma BNP increased to a similar extent in both groups with subcutaneous BNP. In contrast, group 1 had a much greater urinary cGMP excretion (4219 +/- 900 to 8600 +/- 1600 pmol/min; P < 0.05) as compared with group 2 (1954 +/- 300 to 3580 +/- 351 pmol/min; P < 0.05). In experimental overt CHF, chronic administration of PDE V inhibitor did not enhance renal function despite an improvement in cardiac output. However, chronic PDE VI significantly enhanced the renal hemodynamic and excretory responses to exogenous BNP. This study supports a role for PDE V as contributing to renal maladaptation in a model of experimental overt CHF and the strategy of maximizing the renal cGMP system by combined PDE VI and natriuretic peptides in CHF to improve renal function.
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PMID:Maximizing the renal cyclic 3'-5'-guanosine monophosphate system with type V phosphodiesterase inhibition and exogenous natriuretic peptide: a novel strategy to improve renal function in experimental overt heart failure. 1692 3

Complement is a major pro-inflammatory innate immune system whose serum activity correlates with systolic blood pressure in humans. To date, no studies using in vivo models have directly examined the role of individual complement components in regulating vessel function, hypertension and cardiac hypertrophy. Herein, in vivo responses to angiotensin (ang) II were characterized in mice deficient in CD59a or C3. CD59a(-/-) mice had slightly but significantly elevated systolic blood pressure (107.2 +/- 1.7 mmHg versus 113.8 +/- 1.31 mmHg, P < 0.01, for wild-type and CD59a(-/-), respectively). Aortic rings from CD59a(-/-) mice showed significantly less platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, with elevated deposition of membrane attack complex. However, acetylcholine- and sodium nitroprusside-dependent dilatation, plasma nitrate/nitrite and aortic cyclic guanosine monophosphate levels were unchanged from wild-type. Also, in vivo infusion with either ang II or noradrenaline caused similar hypertension and vascular hypertrophy to wild-type. Mice deficient in C3 had similar basal blood pressure to wild type and showed no differences in hypertension or hypertrophy responses to in vivo infusion with ang II. These data indicate that CD59a deficiency is associated with some vascular alterations that may represent early damage occurring as a result of increased complement attack. However, a direct role for CD59a or C3 in modulating development of ang II-dependent hypertension or hypertrophy in vivo is excluded and we suggest caution in development of complement intervention strategies for hypertension and heart failure.
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PMID:CD59 or C3 are not requred for angiotensin II-dependent hypertension or hypertrophy in mice. 1743 74


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