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Arch Int Physiol Biochim. 1989 Apr;97(2):185-96.
[Enzyme activity of cardiac glycogen metabolism: study of an in situ hypoxia protocol in the rat]

[Article in French]

Grably S, Verdys M, Rossi A.

Laboratoire de Physiologie Cellulaire Cardiaque, U.R.A. CNRS no 632, Universite Joseph Fourier, Grenoble, France.

Myocardial hypoxia, induced by arrest of the artificial ventilation of anaesthetized open-chest rats, was utilized in order to study some aspects of the regulation of myocardial glycogen metabolism. Atenolol, a cardioselective beta-adrenergic receptor antagonist, and verapamil, an inhibitor of sarcolemmal calcium transfer, were used to determine the respective role of adenosine 3', 5'-cyclic monophosphate (cAMP) and calcium in the activation of the enzymes of glycogen phosphorolysis and synthesis. Glycogen degradation is reduced by atenolol treatment, as a consequence of a reduced activation of glycogen phosphorylase. Verapamil treatment has no significant effect, neither on the enzyme activation nor on the glycogen utilization. The activation of glycogen synthase, expressed by the conversion of the enzyme from the D to the I form, which results from the decrease in glycogen stores during hypoxia, is lowered under the effect of both drugs. However, in the beta-blocker treatment case, this effect results from a lower glycogen depletion while this effect is more specific in hearts from rats treated with verapamil. Under the effect of verapamil, the reduction of synthase activation, for a similar depletion of glycogen stores, was confirmed by experiments using isolated rat hearts submitted to ischaemia. These results show that: 1. the glycogenolysis in the hypoxic myocardium in situ is mainly controlled by a cAMP-dependent enzyme conversion or by metabolic allosteric effectors; 2. the activation of myocardial glycogen synthase, which is essentially correlated to the reduction of glycogen stores, is also calcium-dependent and most probably totally cAMP-independent.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2476096&dopt=Abstract




Biochem J. 1995 Dec 15;312 ( Pt 3):805-9.
Evidence for receptor and G-protein regulation of a phosphatidylethanolamine-hydrolysing phospholipase A1 in guinea-pig heart microsomes: stimulation of phospholipase A1 activity by DL-isoprenaline and guanine nucleotides.

Badiani K, Arthur G.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

While evidence has been presented for the receptor-mediated activation of phospholipases A2, C and D, the activation of phospholipase A1 subsequent to receptor activation has not been established. Phospholipase A1-catalysed hydrolysis of 1-palmitoyl-2-linoleoyl-glycerophosphoethanolamine (GPE) by guinea-pig heart microsomes was stimulated 40-60% by isoprenaline. This isoprenaline-mediated increase in activity was blocked by propranolol and butoxamine, a specific beta 2-adrenergic antagonist, but not by atenolol, a specific beta 1-adrenergic antagonist. Neither clonidine nor phenylephrine, alpha 1- and alpha 2-adrenergic agonists respectively, had a stimulatory effect on the hydrolysis of the PE substrate. Guanosine 5'(-)[gamma-thio]triphosphate (GTP[S]) and guanosine 5'(-)[beta,gamma-imido]triphosphate, but not guanosine 5'(-)[beta-thio]diphosphate (GDP[S]) or adenosine 5'(-)[gamma-thio]triphosphate, stimulated the hydrolysis of 1-palmitoyl-2-linoleoyl-GPE by phospholipase A1. GDP[S] inhibited the isoprenaline-mediated stimulation of phospholipase A1 activity. Phospholipase A1 hydrolysis of 1-palmitoyl-2-linoleoyl-GPE was not dependent on cations; however, the stimulatory effects of isoprenaline and GTP[S] on the hydrolytic activity were abolished by cation chelators. The above data suggest that phospholipase A1 activity in guinea-pig heart microsomes is activated by the binding of isoprenaline to beta 2-adrenergic receptors. Furthermore the stimulation of phospholipase A1 activity by the agonist may be mediated via activation of G-proteins.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8554524&dopt=Abstract




J Gen Intern Med. 1996 Mar;11(3):139-46.
Implementation of local guidelines for cost-effective management of hypertension. A trial of the firm system.

Aucott JN, Pelecanos E, Dombrowski R, Fuehrer SM, Laich J, Aron DC.

Medical Service, Cleveland Veterans Affairs Medical Center, OH, USA.

OBJECTIVE. To evaluate the effects of an intensive intervention to implement guidelines for cost-effective management of hypertension on medication use and cost, blood pressure control, and other resource use. DESIGN. Retrospective cohort trial based on the Cleveland Veterans' Affairs Medical Center Firm System. SETTING. General internal medicine teaching clinic in a large university-affiliated Department of Veterans Affairs Medical Center. PARTICIPANTS. All patients seen in the intervention firm (n = 1273) and control firm (n = 884) clinics in the 3-month period following the introduction of the guidelines. INTERVENTIONS. The control firm received guidelines and usual education for the cost-effective outpatient management of hypertension. The intervention firm received guidelines plus intensive guideline-based education and supervision. MEASUREMENTS AND MAIN RESULTS. The use of guideline medications was greater in the intervention firm as compared with the control. The intervention firm initiated more hydrochlorothiazide (HCTZ), 17.4% (95% confidence interval [CI] 14.8, 20.1) of patients versus 11.9% (CI 9.3, 14.8) in the control firm (p = .002). Atenolol was initiated in 7.2% (CI 5.6, 9.0) in intervention firm versus 4.7% (CI 3.2, 6.6) in the control (p = .03). In addition, the use of nonguideline medications was less in the intervention firm. The intervention firm initiated less long-acting nifedipine, 7.8% (CI 6.0, 9.8) versus 10.6% (CI 8.2, 13.5) in the control (p = .04). Blood pressure control demonstrated greater improvement in the intervention firm (p = .02). Use of guidelines was associated with decreased costs for antihypertensive medications in the intervention firm as a whole as compared with the control firm. There was no increased use in other measured resources in the intervention firm including the number of outpatient laboratory services obtained, clinic visits, emergency room visits, or hospitalizations. CONCLUSIONS. Intensive implementation of guideline-based education and supervision was associated with an increased use of guideline medications, decreased use of costly alternative agents, and no decrement in the measured outcomes of care.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8667090&dopt=Abstract












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