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)

An enhanced peripheral chemoreflex has been documented in patients with chronic heart failure (CHF). This study aimed to examine the characteristics of carotid body (CB) chemoreceptors in response to isocapnic hypoxia in a rabbit model of pacing-induced CHF and to evaluate the possible role that nitric oxide (NO) plays in the altered characteristics. The chemosensitive characteristics of the CB were evaluated by recording single-unit activity from the carotid sinus nerve in both an intact and a vascularly isolated preparation. It was found that the baseline discharge under normoxia (intact preparation: arterial PO2 90-95 Torr; isolated preparation: PO2 100-110 Torr) and the chemosensitivity in response to graded hypoxia (PO2 40-70 Torr) were enhanced in CHF vs. sham rabbits. These alterations were independent of the CB preparations (intact vs. isolated). NO synthase inhibition by Nomega-nitro-L-arginine increased the baseline discharge and the chemosensitivity in the intact preparation, whereas L-arginine (10(-5) M) inhibited the baseline discharge and the chemosensitivity in the isolated preparation in sham but not in CHF rabbits. S-nitroso-N-acetylpenicillamine, an NO donor, inhibited the baseline discharge and the chemosensitivity in both CB preparations in CHF rabbits but only in the isolated preparation in sham rabbits. The amount of NO produced in vitro by the CB under normoxia was less in CHF rabbits than in sham rabbits (P < 0.05). NO synthase-positive varicosities of nerve fibers within the CB were less in CHF rabbits than in sham rabbits (P < 0.05). These data indicate that an enhanced input from CB occurs in the rabbit model of pacing-induced CHF and that an impairment of NO production may contribute to this alteration.
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PMID:Enhanced activity of carotid body chemoreceptors in rabbits with heart failure: role of nitric oxide. 1019 13

Increased peripheral vascular tone in patients with chronic heart failure (CHF) is an important factor which contributes to increased cardiac afterload and reduced exercise capacity, and consequent further deterioration in CHF. The role of endogenous nitric oxide (NO) in the regulation of basal vascular tone in CHF is controversial. This study has investigated (1) whether basal NO bioavailability is reduced in the peripheral vasculature of patients with nonischemic CHF in the absence of confounding factors influencing endothelial function, and (2) if a difference is found, what clinical characteristics are related to the decreased NO-dependent vasodilation. Basal forearm blood flow (FBF) of 12 patients with CHF and 14 healthy volunteers was measured before and after administration of N(G)-monomethyl-L-arginine (L-NMMA) by venous occlusion plethysmography. After L-NMMA administration, basal FBF in both healthy subjects and patients with CHF decreased significantly, with the decrease in CHF patients being less than that in healthy volunteers (-0.7+/-0.2 vs -1.5+/-0.2 ml/min per 100 ml tissue, P < 0.01). When both groups were considered together, basal FBF was closely related to the decrease in FBF after L-NMMA administration (r = -0.83. P < 0.001). When CHF patients were divided into two groups according to NYHA class, the L-NMMA-induced decrease in FBF in moderate CHF (NYHA III; n = 7) was significantly less than that in mild CHF (NYHA II; n = 5) (-0.36+/-0.13 vs -1.16+/-0.72 ml/min per 100 ml tissue, P < 0.05). In conclusion, basal bioavailability of NO in the peripheral vascular bed in nonischemic CHF is impaired, with an increase in basal vascular tone and with progression of this disorder. This suggests that impaired basal NO bioactivity may make an important contribution to the elevated peripheral vascular tone and expression of symptoms seen in CHF.
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PMID:Effects of nitric oxide inhibition on basal forearm blood flow in patients with nonischemic chronic heart failure. 1032 84

We examined the effects of chronic oral L-arginine treatment on endothelial and cardiovascular function in rats with heart failure induced by coronary artery ligation. Both heart failure and sham-operated rats were treated with either L-arginine in drinking water (12.5 or 50 g/l) or water placebo for 8 weeks following surgery. Plasma L-arginine levels in heart failure rats (153 +/- 11 microM) were lower than sham rats (201 +/- 13 microM, P < 0.05). The lower dose L-arginine treatment improved endothelium-dependent relaxation of isolated aortic rings of heart failure rats, while the higher dose of L-arginine treatment did not. Neither low nor high dose of L-arginine treatment improved hemodynamic parameters in heart failure rats. Thus, chronic oral L-arginine treatment at a dose of 12.5 g/l in drinking water improves endothelium-dependent relaxation, but fails to improve in vivo cardiac function in rats with heart failure.
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PMID:Effects of L-arginine on endothelial and cardiac function in rats with heart failure. 1044 87

We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT(1)-receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT(1)-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 +/- 0.31 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased after ANG II AT(1)-receptor blockade (6.53 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.12 +/- 0.20 ml x 100 g(-1) x min(-1) x mmHg(-1)) and combined inhibition (3.96 +/- 0.57 ml x 100 g(-1) x min(-1) x mmHg(-1); all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 +/- 0.66 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased by ANG II AT(1)-receptor blockade (8.48 +/- 0.83 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.68 +/- 0.22 ml x 100 g(-1) x min(-1) x mmHg(-1); both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.
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PMID:Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats. 1044 15

Recently, we found that amlodipine can release nitric oxide (NO) from canine coronary microvessels, which raises the question of whether amlodipine can also promote coronary NO production in failing human hearts. The goal of this study was to define the effect of amlodipine on NO production in failing human hearts and to determine the role of kinins in the control of NO production induced by amlodipine. Six explanted human hearts with end-stage heart failure were obtained immediately at transplant surgery. Coronary microvessels were isolated as previously described, and nitrite, the stable metabolite of NO in aqueous solution, was measured using the Griess Reaction. Amlodipine (10(-10) to 10(-5) mol/L) significantly increased nitrite production in coronary microvessels in a dose-dependent manner. The increase in nitrite in response to the highest dose of amlodipine (79%) was similar in magnitude to either that of the angiotensin-converting enzyme inhibitor ramiprilat (74%) or the neutral endopeptidase inhibitors phosphoramidon (61%) and thiorphan (72%). Interestingly, the increase in nitrite production induced by amlodipine was entirely abolished by N(omega)-nitro-L-arginine methyl ester and also HOE-140 (a bradykinin-2 antagonist) and dichloroisocoumarin (a serine protease inhibitor that blocks kallikrein activity). These results indicate that amlodipine can promote coronary NO production in failing human hearts and that this effect is dependent on a kinin-mediated mechanism.
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PMID:Amlodipine promotes kinin-mediated nitric oxide production in coronary microvessels of failing human hearts. 1048 Apr 43

We reviewed 12 pediatric and 18 adult patients with short bowel syndrome (SBS) from Osaka University Hospital and compared clinical characteristics between them. The length of the residual small intestine ranged from 0 to 75 cm (mean 47 cm) in pediatric patients and from 0 to 150 cm (mean 47 cm) in adult patients. In all cases, total parenteral nutrition (TPN) was started immediately after surgery and was gradually replaced by enteral nutrition. Eight pediatric patients (67%) and 4 adult patients (22%) were weaned from TPN. Residual intestinal length in these patients ranged from 27 to 75 cm (mean 57 cm) in pediatric patients and 57 to 150 cm (mean 96 cm) in adult patients. Pediatric patients with residual small intestinal lengths of 0, 16, 25, and 45 cm were not weaned from TPN. None of the adult patients with residual small intestinal length less than 40 cm could achieve complete intestinal adaptation. Five adult patients died due to liver failure (2 cases), heart failure (2 cases), or pneumonia (1 case), whereas all pediatric patients survived. The average life span of indwelling central venous catheters was 511 days and 780 days, and the rate of catheter-related sepsis per 1000 catheter days was 0.73 and 0.48 in pediatric and adult patients, respectively. Plasma levels of arginine and citrulline in patients receiving TPN were significantly decreased compared with those in patients receiving TPN without SBS both in pediatric and adult patients (p < .01). These results indicate that pediatric and adult patients with SBS can survive with TPN and enteral nutrition. The minimum remaining intestinal length necessary for complete bowel adaptation is shorter for pediatric patients than adults, suggesting better bowel adaptation in pediatric patients.
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PMID:Long-term outcome of short bowel syndrome in adult and pediatric patients. 1048 9

Pheochromocytomas are rare neoplasias of the adrenal medulla which generally present with paroxysmal or sustained hypertension. Cardiogenic pulmonary edema is a common feature of these tumors, but few cases have been described with noncardiogenic pulmonary edema. We report a pheochromocytoma with the principle manifestation of noncardiogenic pulmonary edema and characterize a genetic lesion associated with the disorder. A 30-year-old man was admitted with abdominal pain and breathlessness. x-Ray examination of the chest revealed a massive, diffuse infiltration of the left lung without cardiomegaly. No paroxysmal blood pressure fluctuations or heart failure were evident during the entire course, and the infiltrate and dyspnea resolved in three days without inotropic or diuretic agents. Serum norepinephrine and epinephrine levels were elevated twenty and fifty times above normal, respectively. The patient was ultimately diagnosed with multiple endocrine neoplasia type 2A (MEN 2A). Mutations in the RET proto-oncogene have been described recently in patients with MEN 2A. Mutation analysis of selected RET exonic sequences identified a germline mutation at codon 634 in exon 11 of the RET proto-oncogene. The mutation introduces a transition encoding a non-conservative substitution from TGC (Cys) to CGC (Arg) and creates a novel restriction site recognized by HhaI. We further screened for this mutation among four of the proband's relatives by HhaI restriction analysis. One asymptomatic family member was identified who subsequently elected prophylactic total thyroid removal. Histological examination of this specimen confirmed the presence of medullary thyroid carcinoma.
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PMID:Noncardiogenic pulmonary edema as the chief manifestation of a pheochromocytoma: a case report of MEN 2A with pedigree analysis of the RET proto-oncogene. 1052 79

Patients in the chronic phase of Chagas' disease suffer from a slowly evolving inflammatory cardiomyopathy that can lead to severe cardiac dilatation, congestive heart failure, and death. This process appears to be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after infection with the parasite Trypanosoma cruzi. Recent evidence suggests that there are circulating antibodies in chronic chagasic patients that alter the physiological behavior of the heart on binding to G-protein-coupled cardiovascular receptors, including beta1-adrenergic and m2 muscarinic receptors. A 42 kDa fusion protein was constructed that contains the central part of the third intracellular loop (i3; Arg(267)-Arg(381)) of the human m2 muscarinic receptor, linked to glutathione S-transferase. This fusion protein was overexpressed in Escherichia coli and subsequently purified by affinity chromatography. Based on Western blots, the i3 loop is specifically recognized by the sera of chronic chagasic patients who have reached advanced stages of cardiac failure (according to the Los Andes classification). Analysis of the prevalence and distribution of these antibodies shows a strong association between seropositive patients and moderate (group II) to severe (group III) heart dysfunction.
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PMID:Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. 1054 84

The cardiovascular role of the neuropeptide Y Y1 receptors in-vivo and in-vitro in ischaemic heart failure was evaluated by using the novel neuropeptide Y Y1 selective antagonist BIBP 3226 (R-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amid e). In pithed rats, incremental doses of BIBP 3226 inhibited the exogenous neuropeptide Y induced pressor response in a dose-related fashion and a bolus injection of BIBP 3226 (0.5 mg kg(-1)) significantly shifted the pressor response curve of exogenous neuropeptide Y to the right. The potentiation effect to exogenous neuropeptide Y on the pressor response to preganglionic sympathetic nerve stimulation in ischaemic heart failure rats as well as on the contractile response to noradrenaline in renal arteries in sham-operated animals were also inhibited by the neuropeptide Y Y1 antagonist. In conscious ischaemic heart failure rats, incremental doses of BIBP 3226 (0.125-1 mg kg(-1)) significantly reduced basal blood pressure and heart rate. Compared with sham-operated rats, neuropeptide Y by itself induced no contraction and no potentiation on noradrenaline elicited contraction in renal artery of the ischaemic heart failure rat. Furthermore, under in-vivo conditions, BIBP 3226 did not influence basal renal function or the response to exogenous neuropeptide Y on urinary volume, urinary sodium and urinary potassium. Our results demonstrate that although there is a downregulation of the Y1 receptors by ischaemic heart failure, Y1 receptors are still mainly involved in cardiovascular actions of exogenous neuropeptide Y and play a role in maintaining basal blood pressure and heart rate in ischaemic heart failure. However, our data do not imply any significant role of Y1 receptors on basal renal function in the ischaemic heart failure rat model.
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PMID:Renal and cardiovascular role of the neuropeptide Y Y1 receptor in ischaemic heart failure rats. 1063 83

The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.
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PMID:Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure. 1064 96


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