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Biomedical subjects

E Bassenge

Publications and source records attributed to E Bassenge.

At least 145 records · Page 8Linked to original sources
PubMed1985

[Regulation of vascular tone by the endothelium].

In the last few years, experimental evidence has accumulated which suggests a substantial role for the endothelium in the control of vascular tone. Endothelium-dependent dilations have been demonstrated in various arteries of numerous mammalian species including man. Among the stimuli which elicit endothelium-dependent dilatation are such different stimuli as increases in blood flow and hypoxia as well as endogenous (acetylcholine, ATP, ADP, bradykinin, substance P) and pharmacological agents (calcium ionophore A 23 187, ergometrine, hydralazine, melittin). The functional importance of endothelium-dependent dilatation is emphasized by the fact that the direct vasoconstrictor effects of some of these substances (acetylcholine, histamine, norepinephrine, serotonin) on vascular smooth muscle is attenuated or even reversed by their simultaneous stimulatory effect on endothelial cells resulting in the release of a vasodilator signal. Bioassay experiments have shown that a humoral vasodilator agent with a biological half-life in the range of seconds is released from the endothelium (native or cultured) during stimulation with acetylcholine, ATP and calcium ionophore. Experimental data are presented which suggest that EDRF may act by direct stimulation of guanylate cyclase, resulting in smooth muscle relaxation due to increased smooth muscle cyclic GMP levels. The chemical nature of this nonprostaglandin endothelium-derived relaxant factor (EDRF) is still not known. The possible physiological and pathophysiological significance of endothelium-dependent dilatation in situ is discussed. Special attention is paid in this context to the potential role of EDRF activity in coronary vasomotor control.

Animals↗
PubMed1984

[Modulation of coronary vessel tonus: molecular and cellular mechanisms].

The cyclic interactions between myosin cross bridges and the actin filament in the presence of Ca++ with a sliding of both filaments passed each other, is considered also in vascular smooth muscle as the basic contractile mechanism. While in the striated muscle the regulation of the actin-myosin interaction occurs at the level of the actin filaments, there is a growing body of evidence that the contractile activation of the vascular smooth muscle is primarily regulated by phosphorylation of the 20,000-Dalton myosin light chain. This reaction is catalyzed by a calcium-calmodulin-dependent myosin light chain kinase. Additionally, dephosphorylated myosin cross bridges which remain attached to actin filaments over prolonged periods of time ("latch bridges") at low myoplasmic Ca2+-concentrations seem to be involved in the vascular smooth muscle in maintaining tonic active stress at a very low energy expenditure. In most arterial smooth muscle cells, the initiation of contraction (electromechanical coupling) is not associated with action potentials, but is coupled with graded membrane depolarization. During the process of excitation-contraction coupling, two mechanisms lead to increased myoplasmic calcium: a) Calcium influx through voltage-dependent channels along an electro-chemical gradient. b) Release of calcium from the sarcoplasmic reticulum or from the inside of the cell membrane, triggered either by calcium influx or directly by membrane depolarization. The pharmaco-mechanical coupling, i.e., the contractile activation by drugs without depolarization as initiating step, seems to be realized only in a few specific vessels. The stimulation of the phosphatidyl-inositol turnover (PI-cycle) in the plasma membrane by activation of alpha 1-adrenergic receptors can also be demonstrated in vascular smooth muscle cells. However, whether or not this PI-response plays a primary role in the increase of myoplasmic Ca2+ remains to be settled. The activation of alpha 2-adrenergic receptors seems to involve the action of an inhibitory guanine nucleotide-binding protein on the catalytic moiety of the adenylate cyclase. Thus, the contractile response observed may be attributed to the decrease of cyclic AMP (which is responsible for dilating effects via phosphorylation of various regulatory proteins). The decrease in the myoplasmic concentration of free-ionized calcium as a basic principle of relaxation comes about by different mechanisms, which can be classified as follows: a) Inhibition of transmembrane calcium influx into vascular smooth muscle cells by Ca-antagonists, which specifically interfere with plasmalemmal Ca2+-channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1984

Development of specific tolerance to nicotine infusions in dogs on chronic nicotine treatment.

Chronic smoking in humans and continuous nicotine application in animals do not induce hypertension, although the acute effects of nicotine are sympathoadrenal activation and elevation of blood pressure. In conscious dogs with a carotid artery loop preparation, we studied whether chronic nicotine application induced tolerance to the acute effects of nicotine test infusions. Nicotine was applied as salicylate via subcutaneously implanted osmotic minipumps at a dosage of 1 microgram/kg/min = 1.44 mg/kg/day, corresponding to heavy smoking in humans. Chronic treatment in eight dogs for 5-8 weeks did not modify resting heart rate and plasma levels of free catecholamines, but significantly increased plasma levels of conjugated dopamine by 100%. Mean arterial pressure at rest was elevated in the 2nd week by 6mm Hg, but did not increase further. Sham treatment (n = 8, sodium salicylate in equivalent dosage) was without effect. Acute test-infusions of nicotine (3 and 10 micrograms/kg/min i.v.) caused acute rises in mean arterial pressure (by 12 and 28 mm Hg), heart rate (by 9 and 18 bpm), plasma norepinephrine (by 36 and 68%), plasma epinephrine (by 110 and 180%) and led to plasma nicotine levels of 31 and 95 ng/ml. Chronic nicotine treatment attenuated the hemodynamic and partially abolished the hormonal effects without affecting the nicotine plasma levels obtained with these test infusions, but it did not modify the hemodynamic effects of a norepinephrine test infusion. The data demonstrate the development of a specific, reversible tolerance to the acute sympathoadrenal activation by nicotine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Tonus of epicardial main arteries and dynamic stenosis].

Under physiologic conditions the tone of the epicardial coronary arteries plays a minimal role in the regulation and distribution of myocardial blood flow. However, under pathophysiologic conditions, especially in coronary heart disease, even small changes in tone may play an eminent role. A uniform mechanism for the induction of excessive coronary constriction and spasm is as yet not recognizable. It is probably a multifactorial event in which different, variable factors add to or potentiate each other. This constriction or spasm inducing chain can with certainty only be interrupted at one of its last links: prevention of an excessive activation of the smooth vascular contractile apparatus through a reduction of the activating calcium influx (calcium antagonists) or through an increase of the intracellular cGMP-content with nitrates (through a not yet identified relaxation procedure). In this brief review constriction-inducing or -potentiating factors are discussed in context with the "dynamic stenosis:" alpha-adrenergic and parasympathetic mechanisms, serotonin, histamine, prostanoids and leukotrienes, finally changes of endothelial factors. Under experimental conditions these factors may bring about a more or less pronounced coronary constriction. In animal experiments it is only possible in mini-pigs with experimental coronary atheromatosis or sclerosis (in combination with experimental endothelial damage) to induce spasm-like constrictions of the large epicardial arteries using histamine or serotonin. Under a variety of clinical conditions the importance of these factors for the induction of dynamic coronary stenoses was shown to be of potential significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1983

Attenuation of sympathetic vasoconstriction by nifedipine: the role of vascular alpha 2-adrenoceptors.

The effects of nifedipine on hindlimb vasoconstriction caused by norepinephrine infusion and sympathetic stimulation (0.1-1.0 Hz) were compared in dogs given 0.12 mg/kg prazosin or 0.3 mg/kg rauwolscine. Constrictions due to stimulation or norephinephrine with prazosin, presumed to be mediated by vascular alpha 2-adrenoceptors, were significantly attenuated by 30 micrograms/kg nifedipine, while constrictions with rauwolscine, presumably alpha 1-mediated, remained unaffected. These data support the hypothesis that the antihypertensive effect of calcium antagonists is based upon interference with alpha 2-mediated sympathetic vasoconstriction.

Animals↗
PubMed1983

Two dilatory mechanisms of anti-anginal drugs on epicardial coronary arteries in vivo: indirect, flow-dependent, endothelium-mediated dilation and direct smooth muscle relaxation.

Potential mechanisms of antianginal drugs involve preload and afterload reduction and a dilation of large conduit coronary arteries without a substantial concomitant dilation of the coronary resistance vessels. We analyzed the dilatory mechanism. It consists of two independent components: a direct effect on the arterial smooth muscle and an indirect, endothelium-mediated, shear-stress-dependent effect on the arterial vasculature. Therefore, we tested the relative contribution of these two components in the dilatory response of large coronaries to various antianginal drugs. In chronically instrumented dogs, the outer diameters and the flow in two coronary branches (left circumflex and descending) were registered continuously. A pneumatic occluder implanted distally to the site of the diameter measurements was used in one branch to control flow rates or to maintain constant flow, independent of arteriolar dilation. Increments in flow of more than 100% were elicited by i.v. injections of adenosine, dipyridamole, nifedipine, diltiazem, verapamil, nitroglycerin, ISDN, and molsidomine. All these agents induced a slowly developing dilation of the epicardial coronary arteries (by more than 100 microns), which reached its maximum 90 s after the onset of the increase in flow (while arterial pressure fell). When flow in one branch was experimentally kept constant, the epicardial dilation by adenosine and dipyridamole was completely offset, while it remained unaffected in the control branch with unrestricted flow. Thus, the dilation of the coronary artery by these two drugs is based on the indirect component, caused by the flow-dependent mechanism, in contrast to nitroglycerin-, molsidomine-, and ISDN-induced dilations, which were not affected at all by experimentally limiting the flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1982

Norepinephrine constricts the canine coronary bed via postsynaptic alpha 2-adrenoceptors.

The effect of alpha 2-blockade (0.3 mg/kg i.v. rauwolscine) and alpha 1-blockade (1.2 mg/kg i.v. prazosin) on coronary constrictions induced by intracoronary injections of azepexole (B-HT 933, alpha 2-agonist, 0.1-10 microgram/kg), phenylephrine (0.3-3 microgram/kg) and norepinephrine (0.001-0.1 microgram/kg) were studied in dog hearts perfused in situ under beta-blockade. Constrictions by azepexole (antagonized by rauwolscine, yet resistant to prazosin and methysergide) demonstrated coronary alpha 2-adrenoceptors. Norepinephrine-induced constrictions were more attenuated (22-fold) by alpha 2-blockade than by alpha 1-blockade (2.6-fold) and thus were mediated mainly by activation of postsynaptic alpha 2-receptors.

Animals↗
PubMed1982

Observations of arterial and venous vasomotion with the absolute induction angiometer.

This paper provides biological illustrations of the applicability and mode of use of intravascular and perivascular absolute induction angiometers. Artifacts and limitations of the method as well as experimental precautions and calibration procedures are discussed. Tracing are presented to illustrate the capabilities of the method in recording pulsatile diameter changes in veins and arteries and to demonstrate its applicability to moving blood vessels as exemplified by the coronary arteries. Both intravascular and perivascular angiometry can detect diameter changes of a few micra in a vessel 1 cm in diameter. The intravascular angiometer is a resilient loop of fine bifilar wire which can be introduced into the blood vessel percutaneously via an angiographic catheter. A perivascular angiometer is an easily deformable loop made of a soft fine wire pair which is draped around a blood vessel and can thus be chronically implanted.

Animals↗
PubMed1982

[Effect of nitrates, nitrate-like substances, calcium antagonists and beta-adrenergic receptor blockers on peripheral circulation].

The effectiveness of organic nitrates in the therapy of angina pectoris can be explained from their direct relaxing action on vascular smooth muscle. At conventional dosage the most important action of nitrates is a pooling of blood in the large systemic venous capacitance vessels which leads to a decrease of central venous pressure and ventricular filling pressure. The resulting reduction in left ventricular volume lowers, at virtually constant arterial pressure, systolic wall tension and hence myocardial oxygen consumption. Only at higher dosage, is a distinct dilatation of systemic resistance vessels affected. The fundamental action of the "Ca antagonists", i.e. the inhibition of transmembrane calcium influx in the myocardium and the vascular smooth muscle, includes various beneficial effects for the treatment of angina pectoris. The lowering of myocardial oxygen consumption after application of calcium antagonist is mainly due 1. to the decrease in afterload of the left ventricle, caused by the relaxation of peripheral resistance vessels, 2. to the reduction in ventricular preload by a peripheral venodilation. By a direct inhibitory effect on the coronary vascular tone, coronary blood flow at rest in patients with angina pectoris increases. In addition, Ca antagonists are very efficacious in relieving angiospastic angina. The primary mode of action of beta-blocking drugs in angina pectoris affects, in contrast to the peripheral mechanisms of nitrates and Ca antagonists, is on the heart directly. By the reduction in the extent of exercise heart rate, the increase in cardiac output and, hence, the mean arterial pressure is also significantly lower during exercise under beta-blockade. Beta-blockers also depress the contractile state of myocardium. Therefore, the main factors of the myocardial oxygen consumption (mean arterial pressure, size of the left ventricle, contractility and heart rate) may be essentially influenced. By the decrease in heart rate and the longer diastolic period a better myocardial oxygen delivery results. Besides the immediate cardiac effects of beta-adrenergic blockade, a decline in peripheral resistance combined with a fall in blood pressure occur in hypertensive patients during long-term drug administration. Different hypotheses have been proposed in the last years to explain the antihypertensive mode of action of beta-blockers. Some possible mechanisms are discussed.

Adrenergic beta-Antagonists↗
PubMed1982

[Pharmacological basis of therapy with molsidomine].

This paper is a synopsis on recent reports dealing with the pharmacological basis of molsidomine-induced circulatory effects. The therapy of coronary insufficiency by molsidomine is based on different pathophysiological and pharmacological mechanisms. The inactive compound molsidomine is metabolized--mainly in the liver--to form the vasoactive and antiaggregatory compound SIN-1 and SIN-1A. Due to the gradual conversion into the active compound, the peak effects are observed only after 15 min (intravenously) or 30 to 60 min (orally). The effects are long-lasting and can be observed up to four to six hours. The c-GMP mediated dilation of various vascular sites comprise mainly the venous system (both small and large veins), resulting in a significant preload reduction, a decrease in cardiac output, a decrease in heart size and circumferential wall stress, a decrease in myocardial oxygen consumption and a therapeutically important improvement of O2-delivery versus myocardial O2-consumption. This effect results in a significant improvement of myocardial ischemia (reducing frequency of anginal attacks, improvement of exercise tolerance and of exercise induced ST-depressions). In animal experiments molsidomine diminishes infarct size and suppresses reperfusion-induced ventricular fibrillation following ischemia. Molsidomine dilates, like nitroglycerin, the large coronary arteries. Therefore, in coronary heart disease, it may improve collateral flow in addition to beneficial effects on subendocardial perfusion resulting from the reduction of ventricular wall stress. In addition to direct dilating effects on collateral vessels an improvement in perfusion of asynergistically contracting ventricular sections has been observed. In contrast to nitroglycerin, effects on peripheral resistance appear only under extremely high dosages and reflex increases in heart rate are rarely observed. In general molsidomine-induced changes (increases) in heart rate, in stroke volume (decreases), and in cardiac output (decreases) are of small magnitude. Recently interesting findings on molsidomine-induced suppression of thrombocyte aggregation, of thromboxan-synthesis inhibition and of increased prostacyclin formation have been presented, which may be important in the improvement of myocardial (micro-) circulation under ischemic conditions.

Angina Pectoris↗
PubMed1978

Phasic registration of venous diameter changes in-situ with the induction angiometer.

The method of induction angiometry has been used for observation of active and passive venous vasomotion, without surgical exposure of the blood vessel. The diameter sensor is a resilient loop introduced into the vasculature through a fine No. 5 French (1 mm i.d.) angiographic catheter or a needle of comparable internal diameter. An extracorporeal a. c. magnet induces an electromotive force (e.m.f.) in the loop which acts as the secondary of a transformer, the electromagnet being the primary. Pulsations in the blood vessel diameter vary the loop area and with it the induced e.m.f. thus providing a linear measure of relative changes in vascular diameter. Changes in the order of 2 micra in a venous diameter of 5 mm can be resolved in-situ. Examples are given of registration of phasic venous diameter changes at the frequencies of the heart beat, respiration and Mayer waves. Pharmacological tests illustrate the ability to detect venous vasomotion in response to a dose below 0.1 microgram/kg of nitroglycerin in dogs.

Animals↗
PubMed1978

Effect of dobutamine, a new cardioselective sympathomimetic drug, on myocardial oxygen balance in conscious dogs.

The effects of (+/-)-4-(2-[3-(p-hydroxyphenyl)-1-methylpropyl]-amino)-ethyl-pyrocatechol hydrochloride (dobutamine) on myocardial O2 balance were investigated in healthy conscious dogs with experimental AV-block. Dobutamine, injected as a bolus of 3, 6, 10 micrograms/kg, increased myocardial contractility, coronary flow, coronary venous O2 saturation and aortic pressure, while initially decreasing SA-node rate. Following ganglionic blockade the effects of dobutamine on myocardial contractility were unchanged while those on coronary flow and coronary venous O2 saturation were reduced by 30%. Aortic pressure and heart rate showed a dose dependent, long-lasting increase. The effects of dobutamine on heart rate and myocardial contractility could be abolished by beta 1-adrenoceptor blockade with practolol (2 mg/kg) while the effects on coronary flow and myocardial O2 extraction were reduced by 40% after practolol. Following beta 1 + 2 adrenoceptor blockade with propranolol, dobutamine increased aortic pressure and coronary flow while coronary resistance and myocardial oxygen extraction were unaffected.

Animals↗
PubMed1977

Exercise induced augmentation of myocardial oxygen extraction in spite of normal coronary dilatory capacity in dogs.

Myocardial O2-extraction rate was studied during exercise induced augmentation of cardiac work in dogs. The O2-extraction rate at rest was 75% of arterial content. Progressive levels of exercise increased the animals' O2-consumption from 7 ml/min-kg up to 91 ml/min-kg. Cardiac output rose from 108 ml/min-kg at rest to 484 ml/min-kg at the highest exercise level. The increase in myocardial O2-consumption from 9 ml/min-100 g at rest up to 57 ml/min-100g at the highest exercise level was met by an increase in coronary flow from 59 to 256 ml/min-100 g and a rise of myocardial AVDO2 from 15 to 22 Vol%. Thus the latter contributed 40% to the augmented myocardial O2-requirements. Coronary venous O2-saturation decreased to 9% saturation during highest levels of exercise. This low value was not the result of a limited coronary dilatory capacity, of inadequate state of exercise training, or of a relative underperfusion of the inner layers of the left ventricle. Thus, augmentation of myocardial O2-extraction rate seems to be a mechanism of physiological relevance during exercise induced elevation of myocardial O2-requirements in dogs and may be explained by capillary recruitment in the myocardium.

Animals↗