Search PubMed⌕ Search

Biomedical subjects

E Bassenge

Publications and source records attributed to E Bassenge.

At least 127 records · Page 7Linked to original sources
PubMed1987

Balance between endothelium-mediated dilating and direct constricting actions of serotonin on resistance vessels in the isolated rabbit heart.

To determine whether endothelium-derived relaxing factor (EDRF) contributes to the vasomotor action of serotonin (5-HT) in the coronary resistance bed, we used haemoglobin as an inhibitor of EDRF in isolated perfused rabbit hearts. The 5-HT-induced dilatation (14 +/- 2% change in vascular resistance) was converted to constriction (10 +/- 3% change) in the presence of haemoglobin, while the vasodilator responses to papaverine were not attenuated. This is consistent with a role for EDRF in the mediation of 5-HT-induced coronary resistance vessel dilatation.

Animals↗
PubMed1987

Reversal of acetylcholine-induced coronary resistance vessel dilation by hemoglobin.

In large arteries, acetylcholine-induced dilation is mediated by endothelium-derived relaxing factor (EDRF) and can be blocked by hemoglobin (Hb). However, the role of EDRF in the microcirculation is uncertain. Therefore, the effect of Hb on acetylcholine-induced dilation of resistance vessels was studied in isolated, constant-flow perfused rabbit hearts. Hb reversibly blocked the acetylcholine-induced lowering of perfusion pressure (control -27 +/- 3%; during Hb 0 +/- 4%) without inhibiting responses to other dilators, strongly suggesting that acetylcholine action in the microcirculation is mediated by EDRF.

Acetylcholine↗
PubMed1987

Endothelium-derived relaxant factor inhibits platelet activation.

Experiments were designed to investigate whether platelet activation is modulated by endothelium-derived relaxant factor (EDRF) which has been shown to induce vascular smooth muscle relaxation by direct stimulation of soluble guanylate cyclase. EDRF was released from cultured bovine endothelial cells, grown on microcarrier beads, by stimulation with thimerosal in the presence of indomethacin. EDRF had no effect on the intracellular free calcium concentration (Cai2+, measured with the fluorescent indicator indo-1) of resting washed human platelets but significantly attenuated the thrombin-induced rise of Cai2+ from 896 +/- 99 (SEM) to 509 +/- 48 nmol/l. EDRF significantly increased platelet cyclic GMP levels from 0.25 +/- 0.04 to 2.5 +/- 0.4 pmol/10(8) platelets and reduced the thrombin-induced aggregation to 23 +/- 3% of control. EDRF had no effect on Cai2+, cyclic GMP or aggregation after a 3 min storage interval, but superoxide dismutase (shown to increase stability of the labile factor) significantly augmented the EDRF effects on Cai2+. The antiaggregatory potency of EDRF was completely abolished in the presence of hemoglobin. The results characterize EDRF as a potent cyclic GMP-dependent antiaggregatory factor which may act synergistically in vivo with the cyclic AMP-dependent inhibitory effect of prostacyclin.

Animals↗
PubMed1987

Dilation of epicardial arteries in conscious dogs induced by angiotensin-converting enzyme inhibition with enalaprilat.

Vasodilators may provoke myocardial ischemia in patients with coronary heart disease. Therefore, we analyzed in conscious dogs the effect of angiotensin-converting enzyme (ACE) inhibition by enalaprilat on parameters potentially important to provocation of myocardial ischemia, such as sympathetic activity, myocardial oxygen consumption, and vascular tone in coronary conduit and resistance vessels. Under normal sodium intake (2-4 mEq/kg/day), enalaprilat (0.03 and 0.3 mg/kg i.v. during 5-min infusion with 30-min intervals, n = 8) did not modify the norepinephrine release rate into plasma (a parameter of overall sympathetic activity). The higher dosage reduced myocardial oxygen consumption (to 87 +/- 2% of control), mean arterial pressure (MAP) (to 90 +/- 1%) and coronary conduit artery tone (normalized delta diameter: +3.2 +/- 0.7%) without dilating coronary resistance vessels. Following renin-angiotensin activation by sodium deprivation (3 X 1 mg/kg furosemide plus 7 days sodium intake less than 0.2 mEq/day), enalaprilat similarly lowered myocardial oxygen consumption and reduced vascular tone both in coronary conduit (normalized delta diameter: +4.0 +/- 0.9%) and resistance vessels (delta coronary flow: +45 +/- 12%). Although MAP declined to 76 +/- 6%, heart rate and norepinephrine release rate were not modified significantly. We propose that the dilation of epicardial arteries results from a direct intramural action. Enalaprilat seems unlikely to provoke myocardial ischemia even in states with a strongly activated renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs.

We examined the effect of nitroglycerin (GTN) tolerance on an important determinant of nitrate-antianginal action, large coronary artery dilation, in 11 chronically instrumented conscious dogs. In addition, endothelium-mediated coronary artery dilation was studied because this shares a common dilator pathway with the nitrates, i.e., activation of soluble guanylate cyclase. With long-term GTN (1.5 micrograms/kg/min iv for 5 days) the diameters of the left circumflex and anterior descending coronary arteries showed an initial increase of 8.2 +/- 0.3% and 10.8 +/- 0.9%, respectively, returning to control levels by the second to third day of treatment. On days 4 and 5, the dose-response relations for GTN-induced epicardial artery dilation were shifted (p less than .01) to 17- to 20-fold higher doses. However, there was no attenuation of epicardial artery dilation induced by SIN-1 (n = 7), another activator of guanylate cyclase, or of endothelium-mediated dilation assessed both as flow-dependent dilation (n = 7) and as direct intra-arterial acetylcholine-induced dilation (n = 4). In addition, there was no clear tolerance to the peripheral vascular actions of GTN responsible for reflex tachycardia and increased coronary flow. We conclude that a moderate degree of nitrate tolerance to epicardial artery dilation does not affect the responsiveness to other exogenous or endogenous activators of guanylate cyclase. However, this tolerance to epicardial artery dilation, together with the maintenance of peripheral vascular actions that can induce reflex tachycardia, result in a potentially unfavorable balance of GTN effects.

Acetylcholine↗
PubMed1987

Characterization of vascular relaxant factor released from cultured endothelial cells.

Cultured bovine endothelial cells were grown on microcarrier beads. Columns (0.2 ml) packed with microcarriers were perfused with oxygenated (20% O2) Tyrode's solution containing indomethacin (10 microM), and the effluent was passed through precontracted, endothelium-denuded detector arteries. When the endothelial cells were stimulated with bradykinin (3-100 nM), adenosine 5'-triphosphate (0.3-30 microM), or calcium ionophore A23187 (10-300 nM), they released dose-dependently a nonprostanoid compound that dilated the detector vessel. The factor, probably identical to the endothelium-derived relaxing factor of native endothelium, evoked dilations of the same magnitude in different types of detector vessels (rabbit thoracic aorta, rabbit femoral artery, canine coronary artery). However, this relaxant factor was significantly more effective in arteries precontracted by norepinephrine or serotonin than in arteries precontracted by potassium depolarization. Thus, its dilator action resembles that of the nitrovasodilators. The factor is labile, with an apparent half-life in the range of 20 to 30 seconds. Its dilator potency was inhibited by dithiothreitol (0.2 mM), metyrapone (0.2 mM), nordihydroguaiaretic acid (20 microM), and hemoglobin (1 microM), all of which apparently inactivated the factor. Synthesis or release (or both) of the relaxant factor was abolished by methylene blue (1 microM). High PO2 levels (greater than 400 mm Hg) in the perfusate markedly reduced the release of the relaxant factor from the cultured cells. This study demonstrates that a vascular relaxant factor is released from endothelial cells in monoculture by adenosine 5'-triphosphate, bradykinin, and A23187 and establishes such a culture as a useful tool for analyzing the mechanisms of endothelium-dependent vasomotion.

Adenosine Triphosphate↗
PubMed1987

Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs.

In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Atrial natriuretic hormone in the human].

The muscle cells of cardiac atria contain many secretory granula with a prohormone of 126 amino acids (ANF(1-126)). Distension of the atria causes exocytosis of the granula with cleavage of the prohormone into the hormone ANF(99-126) or alpha-ANP and the N-terminal fragment ANF(1-98) with an as yet unknown role. The plasma concentration of the hormone in normal man is in the range of 10 pM (30 pg/ml) with a plasma half-life of several minutes and a release rate of 2-3 ng/kg per minute. The plasma concentration changes in parallel with the intake of sodium chloride and is elevated acutely by all interventions which increase the blood volume, or which cause its redistribution towards the cardiopulmonary compartment. Infusions of the hormone cause diuresis and natriuresis, inhibition of the renin-angiotensin-aldosterone system and of sympathetic activity and augmentation of tissue filtration. Thus, a hormonal feedback loop for cardiac unloading by limiting the plasma volume could be assumed. However, the ANF infusion rates necessary for eliciting these actions in man induce ANF plasma concentrations above physiological levels. On the other hand, a physiological role of the hormone in this regulation is suggested by observations during long-term administration of the hormone, which demonstrate actions of the hormone at physiological plasma levels. Furthermore, experiments with injection of ANF antibodies indicate a synergistic action of ANF, together with reflexes in response to atrial distension. ANF acts by activating specific high affinity membrane receptors, resulting in intracellular cGMP formation and cGMP release into plasma and urine. These ANF receptors are "down-regulated" by infusions of the hormone and by chronic volume expansion. In fetal circulation and in congestive heart failure, there is also augmented prohormone synthesis in the cardiac ventricles, which may then contribute to the release of the hormone. Although during cardiac failure the ANF plasma levels are augmented up to 30-fold, and the atrial prohormone content is reduced, there is no indication for an exhaustion of hormone synthesis or for resetting of stimulated hormone release. In addition to its role as a peripheral hormone for "cardiac unloading", ANF occurs in the central nervous system as a neuropeptide, which might also be involved in blood pressure and volume regulation.

Atrial Natriuretic Factor↗
PubMed1987

Abluminal release and asymmetrical response of the rabbit arterial wall to endothelium-derived relaxing factor.

A marked functional polarity of endothelial cells as well as an asymmetry of the vascular wall in response to vasoactive compounds is well established. Therefore, we investigated the polarity of endothelium-derived relaxant factor (EDRF) release from native endothelial cells, its diffusion characteristics, and its dilator effects on inner and outer muscle layers of the vascular wall in isolated rabbit arteries. Following exposure of rabbit aortae (with intact endothelium) to the EDRF stimulators acetylcholine, A23187, or thimerosal, a humoral dilator compound could be assayed in the adventitial superfusate of the vessels. The vasodilator effects were blocked by the EDRF inhibitors hemoglobin, dithiothreitol, and gossypol. Penetration of the dilator through the arterial wall following stimulation by acetylcholine, A23187, or thimerosal was observed only when dilator EDRF activity in the luminal perfusate was maximal. Luminally administered EDRF, released from cultured endothelial cells, did not cross the aortic wall in detectable amounts. EDRF (from cultured cells) elicited significantly smaller dilations (9 +/- 4%) when applied to the adventitial side of endothelium-denuded rabbit aortae or femoral arteries as compared with luminal application (92 +/- 7%). In contrast, sodium nitroprusside was equieffective by both routes of administration. We conclude that EDRF in native endothelial cells is released in both luminal and abluminal directions and can penetrate the entire vascular wall. However, the lengthy diffusion time and the decreasing sensitivity of outer smooth muscle layers suggest that mechanisms other than EDRF diffusion contribute significantly to the propagation of endothelium-mediated relaxation through the arterial wall.

Acetylcholine↗
PubMed1986

In vivo atrial peptide-venodilation: minimal potency relative to nitroglycerin in dogs.

Venodilation is thought to contribute to the hemodynamic actions of atrial peptides. Therefore, we measured the effective vascular compliance (EVC) as a parameter of overall venous tone in 7 pentobarbital anesthetized dogs under autonomic blockade during i.v. infusions of rat atriopeptin II (AP II, up to 100 pmol/kg/min), rat alpha-atrial natriuretic factor, and nitroglycerin (GTN). AP II lowered mean arterial pressure by reducing peripheral vascular resistance with a threshold between 3 and 10 pmol/kg/min (but was ineffective in anesthetized or conscious dogs without autonomic blockade). Neither atrial peptide altered EVC, while GTN augmented EVC and caused a 4.6-fold larger reduction of central venous pressure than AP II at equihypotensive dosage. These findings, with infusion rates probably close to endogeneous release, reveal a vasodilator potency of atrial peptides, which is restricted to systemic arterioles without affecting venous tone.

Animals↗
PubMed1986

Dose-dependent effects of isosorbide-5-mononitrate on the venous, arterial and coronary arterial system of conscious dogs.

Isosorbide-5-mononitrate (IS-5-MN), the main metabolite of isosorbide dinitrate shows antianginal efficacy and is being used increasingly as a drug for practical therapy. In conscious dogs we therefore measured the effects of increasing doses of IS-5-MN on hemodynamic parameters and the diameter of the circumflex artery. We found a dose dependent reduction of the mean right atrial pressure, the systolic blood pressure and a dilatation of the circumflex artery. For all three parameters threshold dosages were between 0.01 and 0.03 mg/kg. On the contrary peripheral and coronary resistance did not change at doses less than or equal to 0.3 mg/kg. The heart rate was significantly increased only at doses above 1 mg/kg and the diastolic blood pressure also showed a tendency to fall only at doses above 1 mg/kg. Cardiac output and coronary flow were not significantly altered over the entire dose range investigated, with the exception of a transient rise in coronary blood flow after the injection of 2.5 mg/kg IS-5-MN. From our results we can deduce that in the low dose range reduction of preload and dilatation of large arteries are the main effects of IS-5-MN. In contrast, no reduction of the coronary or peripheral resistance is to be expected.

Animals↗
PubMed1986

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) under autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 micrograms/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 +/- 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 micrograms/kg/min) induced a 15 +/- 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 +/- 10% increase in norepinephrine release rate. We conclude that modest long-term exposure to nitroglycerin results in tolerance to its venodilating effects, whereas arteriolar action is maintained. This tolerance-induced shift in action from venous toward arteriolar dilation is normally masked by compensatory reflexes.

Animals↗
PubMed1986

Crucial role of endothelium in the vasodilator response to increased flow in vivo.

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.

Acetylcholine↗
PubMed1986

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone.

Adrenergic alpha-Antagonists↗
PubMed1986

Effects of nitrates in various vascular sections and regions.

Recently there has been much progress towards defining the action of nitrates, and related compounds, at a biochemical level. However, in vivo, differences in the effects of nitroglycerin (GTN) between specific sections of the vascular tree and various regions of the circulation are still not well understood. The actions of nitrates as they relate to the alleviation of myocardial ischemia are briefly reviewed. Then, an attempt is made to analyze separately the nitrodilator influences in the large and medium sized arteries, the venous system and the arterioles, in vivo. When pitfalls such as nonselectivity of indexes of drug action and secondary compensatory regulatory influences are considered, a surprising responsiveness of the resistance vessels to GTN is unmasked, revealing a remarkable uniformity in the profile of GTN action within different sections of the vascular tree. Nitrate effects in these vascular sections are then compared among several important regions of the circulation (i.e. mesenteric, skeletal muscle, brain etc.), and similarities or differences in action are noted. Finally the concepts presented here are related to some areas of controversy regarding nitrate action, in an attempt to form a basis for a better understanding of the sometimes confusing nitrate literature.

Animals↗
PubMed1985

Effect of molsidomine on cardiac preload, coronary artery diameter, and coronary resistance.

The vascular and hemodynamic effects of a single intravenous bolus injection of molsidomine (100 micrograms/kg) were studied in six chronically instrumented, conscious dogs. At this dose only a minimal, short-term effect on peripheral resistance was observed. However, there was a pronounced dilation of peripheral veins and a simultaneous increase of effective vascular compliance of more than 60%. At the same time, central blood volume decreased significantly (17%). Because of preload reduction, left ventricular end-diastolic volume and pressure decreased significantly for more than 1 hour. A significant increase of large coronary artery diameter (up to 7% occurred simultaneously. Coronary resistance vessels were not affected. All effects reached a maximum between 15 and 30 minutes and were observed for at least 4 hours. We conclude that molsidomine exerts a long-lasting effect on the large coronary arteries and on the peripheral venous system. As a result of the combined effects on cardiac preload and on epicardial artery conductance, the myocardial oxygen supply and the supply/demand ratio will be improved.

Animals↗