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)

The effects of separate and combined endopeptidase inhibition (by SCH-32615) and natriuretic peptide receptor C blockade [by C-ANP-(4-23)] on the clearance and bioactivity of atrial (ANP) and brain (BNP) natriuretic peptides was investigated in eight sheep with heart failure. SCH-32615 and C-ANP-(4-23) administered separately induced significant and proportionate dose-dependent rises in plasma ANP, BNP, and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Associated with these changes were reductions in arterial pressure, left atrial pressure, and peripheral resistance and increases in cardiac output, urine volume, sodium excretion, and creatinine clearance. SCH-32615 induced greater diuresis and natriuresis than C-ANP-(4-23). Combined administration of SCH-32615 and C-ANP-(4-23) induced greater than additive rises in plasma ANP, BNP, and cGMP concentrations, with enhanced hemodynamic effects, diuresis, and natriuresis and reduced plasma aldosterone levels. In conclusion, we find that the enzymatic and receptor clearance pathways contribute equally to the metabolism of endogenous ANP and BNP in sheep with heart failure. Combined inhibition of both degradative pathways was associated with enhanced hormonal, hemodynamic, and renal effects and may have greater potential therapeutic value than either agent separately.
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PMID:Clearance receptors and endopeptidase: equal role in natriuretic peptide metabolism in heart failure. 937 74

Heart failure (HF) is a multifactorial and progressive disease that has been linked to activation of the renin-angiotensin and sympathetic systems. In recent years, beta-blockers have been shown to improve the status of HF patients, although the precise mechanisms remain unclear. The present study evaluates the effect of beta-blockade with carvedilol (1 mg/kg/day) on cardiovascular function in 2- and 6-month-old cardiomyopathic hamsters (SCH) after 1-month and 5-month treatment periods with the drug, respectively. Age-matched golden hamsters were used as controls (CT). Systolic blood pressure (SBP) and echocardiographic studies were evaluated. The latter studies included left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes, ejection fraction (EF), cardiac output index (COI), heart rate (HR), and left ventricular posterior wall thickness (LVPWT). In 2-month-old SCH, carvedilol administration during a 1-month period reduced SBP from 107.59 +/- 3.49 to 77.26 +/- 3.49 mm Hg (n = 5, p < 0.05). At this stage, cardiac parameters in SCH were similar to those of controls and were not affected by carvedilol administration. In 6-month-old SCH, 5-month administration of carvedilol decreased SBP from 102.16 +/- 3.61 to 90.60 +/- 2.80 mm Hg (n = 5, p < 0.05), HR from 363 +/- 14 to 324 +/- 14 bpm (n = 5, p < 0.05), and LVESV from 0.18 +/- 0.01 to 0.13 +/- 0.01 ml/100 g BW (n = 5, p < 0.05), and increased EF and COI by 14 and 23%, respectively (n = 5, p < 0.05). The drug did not modify LVEDV or LVPWT. These results reveal that carvedilol significantly improves cardiac function in 6-month-old cardiomyopathic hamsters, but it does not prevent ventricular dilatation. Improved cardiac function appears to be secondary to decreased total peripheral resistance, due mainly to the vasodilator properties of the drug. Thus, overactivation of the sympathetic system is not likely to be a determining factor in the etiology of dilated cardiomyopathy in this animal model.
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PMID:Chronic administration of carvedilol improves cardiac function in 6-month-old Syrian cardiomyopathic hamsters. 1753 24

Dopamine is used to treat heart failure, particularly after cardiac surgery in infants, but the mechanisms of action are unclear. We investigated differences in the effect of dopamine on L-type calcium current (I(Ca)) between newborn (NB, 1-4 days) and adult (AD, 3-4 mo) rabbit ventricular myocytes. Myocytes were enzymatically dissociated from NB and AD rabbit hearts. I(Ca) was recorded by using the whole cell patch-clamp technique. mRNA levels of cardiac dopamine receptor type 1 (D1), type 2 (D2), and beta-adrenergic receptors (beta-ARs) were measured by real-time RT-PCR. Dopamine (100 microM) increased I(Ca) more in NB (E(max) 87 +/- 10%) than in AD ventricular cells (E(max) 21 +/- 3%). Further investigation of this difference showed that mRNA levels of the D1 receptor were significantly higher in NB, and, with beta-AR blockade, dopamine increased I(Ca) more in NB than AD cells. Additionally, SKF-38393 (selective D1 receptor agonist) significantly increased I(Ca) by 55 +/- 4% in NB (P < 0.05, n = 4) and by 11 +/- 1% in AD (P < 0.05, n = 6). Dopamine in the presence of SCH-23390 (D1 receptor antagonist) increased I(Ca) in NB cells by 67 +/- 5% and by 22 +/- 2% in AD cells, suggesting a role for beta-AR stimulation. Selective blockade of beta(1)- or beta(2)-receptors (with block of D1 receptors) showed that the beta-AR action of dopamine in the NB was largely mediated via beta(2)-AR activation. Dopamine produces a larger increase in I(Ca) in NB cardiomyocytes compared with ADs. The mechanism of action is not only through beta(2)-ARs but also due to higher expression of cardiac D1 receptor in NB.
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PMID:Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and beta2 receptors. 1837 20


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