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Biomedical subjects

H R Besch

Publications and source records attributed to H R Besch.

At least 55 records · Page 3Linked to original sources
PubMed1978

Role of microtubules in granulocyte adherence.

The adherence of human polymorphonuclear leukocytes (PMN) to nylon fibers is inhibited in a dose-dependent fashion by exposure in vitro of these cells to either colchicine or VM-26, both of which agents prevent microtubule assembly. Mean adherence of human PMN was 48% +/- 2%, following treatment with 10(-5) M colchicine or 10(-4) M VM-26 it was reduced to 31% +/- 2% and 7%, respectively. Peritoneal PMN obtained from mice and mink with Chediak-Higashi syndrome (CHS) thought to have a microtubule-membrane disorder affecting the PMN had a mean adherence of 29% +/- 3% and 40% +/- 8% compared to control values of 46% +/- 5% and 73% +/- 8%, respectively, from the mice and mink. Both ascorbic acid and bethanechol, shown previously to enhance microtubule assembly in humans with CHS, normalized granulocyte adherence in PMN obtained from mice with CHS. Cyclic nucleotide levels were not altered by treatment of human PMN with colchicine, nor did they differ between normal and CHS animals. Thus it appears that the state of microtubule assembly may directly affect the properties of the PMN plasma membrane without requiring alterations of cyclic nucleotides as an intermediary.

Animals↗
PubMed1977

Thyroid hormone regulation of beta-adrenergic receptor number.

The effects of exogenous thyroid hormones (thyroxine and triiodothyronine) on beta-adrenergic receptors in the rat myocardium were investigated. The potent beta-adrenergic antagonist, (-)-[3H]dihydroalprenolol, was used to directly estimate the number and affinity of beta-adrenergic receptors in rat heart membranes from control and hyperthyroid rats. Cardiac membranes from hyperthyroid rats contained 196 +/- 7 fmol of (-)-[3H]dihydroalprenolol binding sites/mg of protein which was significantly (p less than 0.005) greater than the number of binding sites (89 +/- 5 fmol/mg of protein) present in control membranes. The equilibrium dissociation constant (KD) for the interaction of receptors with dihydroalprenolol was the same (2 to 15 nM) in membranes from control and hyperthyroid rats. Similarly, there was no significant difference between the control and hyperthyroid membranes in the affinity of the beta-adrenergic receptor binding sites for the beta-adrenergic agonist isoproterenol. The results of this study demonstrate that thyroid hormones can regulate the number of cardiac beta-adrenergic receptors. The increased numbers of receptors may be responsible, at least in part, for the enhanced catecholamine sensitivity of beta-adrenergic-coupled cardiac responses in the hyperthyroid state.

Adrenergic beta-Antagonists↗
PubMed1977

alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.

We determined the effect of alpha-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of alpha-adrenergic receptors with either phenylephrine (10(-8) M to 10(-6) M) or epinephrine (10(-8) M to 10(-6) M) plus propranolol (10(-6) M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10(-6) M). Phenylephrine (10(-5)M attenuated cyclic AMP generation in response to isoproterenol (10(-8) M and 10(-5) M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10(-6) M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by beta-adrenergic receptors, whereas decreases appear to by mediated by alpha-adrenergic receptors.

Adrenergic alpha-Agonists↗
PubMed1977

Binding and effect of tritiated quinidine on cardiac subcellular enzyme systems: sarcomplasmic reticulum vesicles, mitochondria and Na+, K+-adenosine triphosphatase.

A tritium-labeled derivative of quinidine (D3HQ) was used to assess binding and effect of this drug on isolated membrane preparations from myocardium. D3HG bound to sarcoplasmic reticulum vesicles (SRV) and diminished both Ca++ binding and Ca++ uptake activity. Binding of more than 19 nmol of D3HQ were required to displace 1 nmol of Ca++. Dual-wavelength spectrophotometric methods for monitoring the alterations in Ca++ binding showed that D3HQ depressed maximal Ca++ binding and hastened the onset of Ca++ release from Ca++-loaded SRV, but did not alter the maximal rate of Ca++ release. D3HG also diminished Ca++ sequestration by isolated cardiac mitochondria but the level of D3HQ binding did not correlate with the degree of inhibition. Binding of D3HQ to Na+, K+-adenosine triphosphatase also occurred to a limited extent and a partial inhibition of enzyme activity resulted. A reciprocal relationship between D3HQ binding and a decrease in functional activity of the subcellular membrane systems could be demonstrated only for SRV. The results suggest that cinchona alkaloids might affect myocardial contractility by their effects on Ca++ handling by SRV.

Adenosine Triphosphatases↗
PubMed1976

Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate.

Because ascorbate potentiates chemotaxis of normal leukocytes, we examined the effect of ascorbate on polymorphonuclear leukocytes from a patient with the Chediak-Higashi syndrome. Chemotactic migration was 104+/-16 leukocytes per 10 fields (mean+/-S.D.) initially and 258+/-44 (P less than 0.001) after ascorbate, as compared to 182+/-10 in controls. There was no bactericidal activity by 40 minutes in the patient's untreated leukocytes. After ascorbate bactericidal activity of patient and untreated control cells was the same. The addition of ascorbate reduced cAMP levels in the patient's cells from a mean of 34.5 pmoles per 10(7) polymorphonuclear leukocytes to 5.9, as compared to a control value of 3.1+/-1.4. The association of elevated cAMP and impaired function in the polymorphonuclear leukocytes of patients with the Chediak-Higashi syndrome may be related to abnormal microtubular assembly.

Ascorbic Acid↗
PubMed1976

Sympathetic nerve activity: role in regulation of blood pressure in the spontaenously hypertensive rat.

Sympathetic nerve activity (SNA) and high pressure baroreceptor regulation of SNA were studied in the Okamoto strain of spontaneously hypertensive rat (SHR). Mean arterial pressure (MAP) and SNA were not significantly affected by anesthesia with low doses of pentobarbital (20-25 mg/kg). Thus, most of these studies were performed in anesthetized rats. SNA in visceral sympathetic nerves increased rapidly with age up to 24 weeks and slowly thereafter. MAP increased with SNA, following the same time course. Both SNA and MAP in SHR were significantly greater than that found in normotensive Wistar control rats of comparable ages. Abolition of ganglionic transmission with hexamethonium in both SHR and normotensive controls reduced postganglionic SNA and MAP to comparable levels. In SHR less than 16 weeks old, increased baroreceptor stimulation effectively inhibited SNA with the same sensitivity as found in Wistar control rats. However, older SHR appeared to lose their ability to completely inhibit SNA during induced hypertension, whereas in Wistar control rats as old as 52 weeks, elevation of blood pressure to 165.3 +/- 2.3 mm Hg completely suppressed SNA. These results suggest that SNA may play an important role in the development and maintenance of hypertension in SHR, and that central sympathetic centers, uninhibited by baroreceptor afferents, become active during the development of hypertension in the SHR.

Age Factors↗
PubMed1976

Intact vesicles of canine cardiac sarcolemma: evidence from vectorial properties of Na+, K+-ATPase.

Most biological membranes are functionally asymmetric. To study biochemical control of cardiac transsarcolemmalion fluxes, it would be of obvious advantage to use isolated vesicles of sarcolemma which retains the low passive permeability characteristics of intact sarcolemma because in such vesicles the membrane should exhibit its normal asymmetric character with respect to enzymic activities. The purpose of this investigation was to attempt identify such vesicles in a cardiac microsomal (membrane vesicular) preparation. We studied activation by Na+ and K+ of Na+, K+-ATPase and its associated K+-phosphatase activities, using as substrates ATP or p-nitrophenylphosphate (pNPP) in the presence of Mg2+. Optimal concentrations of K+ alone (10 mM) stimulated p-nitrophenylphosphatase (pNPPase) activity 1.8-fold, and over 80% of the increase could be inhibited by ouabain. Optimal Na+ plus K+ concentrations (100 mM and 10 mM, respectively) stimulated the rate of ATP hydrolysis 2-fold, but only 11 +/- 1.1% of the increased activity was ouabain-sensitive. Optimal pretreatment with sodium dodecyl sulfate (SDS) (0.3 mg/ml) rendered both activities completely sensitive to inhibition by ouabain and reduced the basal Mg2+-ATPase activity by 70-90%. The K+-stimulated pNPPase activity doubled after preincubation in SDS, but the ATPase activity stimulated by Na+ plus K+ fell by 50% under these conditions. A similar pattern of apparent activation was produced by preincubation with deoxycholate (DOC), except that basal Mg2+-dependent activities were resistant to destruction by this detergent. The incremental responses to activation by ions and substrates, and inhibition by oubain, are consistent with the hypothesis that permeability-intact vesicles of sarcolemma are present in the isolated preparation, and that detergent activation renders the vesicles highly permeable to the ions, substrates, and ouabain.

4-Nitrophenylphosphatase↗
PubMed1975

Cardiotonic steroids II: 3-deoxycardenolides and 3-deoxycardanolides.

A series of compounds related to 3-deoxydigitoxigenin was prepared and assayed for inhibition of myocardial Na+,K+- adenosine triphosphatase. Although the relatively high activity of 3-deoxydigitoxin was confirmed, the corresponding 3beta,4beta-epoxide and a mixture of 2,3-olefins and 3,4-olefins were less active. 3-Deoxy compounds with variations at the 14-position and the butenolide ring were much less active than the corresponding 3beta-hydroxy analogs. Thus the activity of 3-deoxydigitoxigenin appears to be particularly susceptible to structural changes elsewhere in the molecule.

Adenosine Triphosphatases↗
PubMed1975

Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.

The purpose of this study was to examine the mechanisms underlying adrenergic-cholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measure in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the intropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.

Acetylcholine↗
PubMed1975

Role of free calcium and ATP in calcium release from cardiac sarcoplasmic reticulum fragments.

Using both isotopic and spectrophotometric techniques to monitor the overall Ca++ binding and release reactions, we have studied the effects of the relative free concentrations of Ca++, sarcoplasmic reticulum fragments (SRF) protein, and ATP on spontaneous Ca++ release by SRF isolated from normal canine hearts. Low free [Ca++] was achieved by using a Ca-EGTA buffer; higher (micromolar) values were obtained by direct Ca++ additions throughout the reactions. ATP concentrations were stabilized by an ATP-regenerating system or an ATP trap. Concentrations of nucleotides in the reaction mixtures were also determined. Release depended in part on the [Ca++]/[ATP] and on the [ATP]. Spontaneous Ca++ release was prevented or slowed when the [ATP] was rapidly lowered with the ATP trap. ATP regeneration delayed, but did not prevent Ca++ release. Ca++-induced Ca++ release was found in the presence of ADP and ATP. Verapamil and D 600 did not affect release. The results may provide a basis for the slowed Ca++ release in SRF from failing hearts.

Adenosine Diphosphate↗