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 myocardial response to catecholamines is significantly diminished in many types of shock or heart failure. The guinea pig heart is an ideal model for the study of shock, as it is relatively inexpensive, and the cardiovascular system of the guinea pig most closely resembles that of the human. Using this model, we have developed techniques to characterize and quantitate changes in beta-adrenergic receptors (beta AR) in the guinea pig heart after burn injury. Preliminary experiments were performed to determine the optimum binding conditions, e.g., incubation time and conditions, protein concentrations, rinsing, etc. Additional experiments were conducted using agonists and antagonists to characterize the rank order of potency and stereospecificity of the beta AR. Crude membrane preparations (50 micrograms/250 microliters) from sham-burned and burned hearts were incubated with 8-10 concentrations of 125I-cyanopindolol (10-450 pM) at 37 degrees C for 1 hr. Under these conditions, binding assays were linear with respect to protein concentration and time. Alprenolol (10 microM) was used to determine nonspecific binding. The membrane preparations used in this study bound both agonists and antagonists with a rank order of potency and stereospecificity characteristic of a beta-adrenergic receptor. Finally, agonist competition curves were performed with isoproterenol in the presence and absence of Gpp(NH)p to determine receptor regulation by the Gs protein. Analysis using computer-assisted techniques suggests that the fraction of high-affinity beta-receptors is significantly reduced after burn injury (41.2 +/- 4.7%) compared to sham-burned controls (54 +/- 2%, P < or = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of cardiac beta-adrenergic receptors in the guinea pig heart: application to study of beta-adrenergic receptors in shock models. 823 Nov 71

The clinical effects of treatment with beta-adrenoceptor (beta-AR) agonists and antagonists in heart failure vary with duration of therapy, as do the effects of beta-AR agonists in asthma. Therefore, we hypothesized that chronic effects of "beta-blockers" in asthma may differ from those observed acutely. We tested this hypothesis in an antigen (ovalbumin)-driven murine model of asthma. Airway resistance responses (Raw) to the muscarinic agonist methacholine were measured by using the forced oscillation technique. In comparison with nontreated asthmatic mice, we observed that: (i) The beta-AR antagonists nadolol or carvedilol, given as a single i.v. injection (acute treatment) 15 min before methacholine, increased methacholine-elicited peak Raw values by 33.7% and 67.7% (P < 0.05), respectively; when either drug was administered for 28 days (chronic treatment), the peak Raw values were decreased by 43% (P < 0.05) and 22.9% (P < 0.05), respectively. (ii) Chronic treatment with nadolol or carvedilol significantly increased beta-AR densities in lung membranes by 719% and 828%, respectively. (iii) Alprenolol, a beta-blocker with partial agonist properties at beta-ARs, behaved as a beta-AR agonist, and acutely reduced peak Raw value by 75.7% (P < 0.05); chronically, it did not alter Raw. (iv) Salbutamol, a beta-AR partial agonist, acutely decreased peak Raw by 41.1%; chronically, it did not alter Raw. (v) None of the beta-blockers produced significant changes in eosinophil number recovered in bronchoalveolar lavage. These results suggest that beta-AR agonists and beta-blockers with inverse agonist properties may exert reciprocating effects on cellular signaling dependent on duration of administration.
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PMID:Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. 1506 6