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Biomedical subjects

T F Lüscher

Publications and source records attributed to T F Lüscher.

At least 19 recordsLinked to original sources
PubMed1992

[Drug-induced hyperprolactinemia and galactorrhea].

A 21 year old female treated for recurring gastric troubles with dopamine-antagonists (domperidone, metoclopramide) developed a clinically manifest hyperprolactinemia (3055 microU/l; normal value < 650 microU/l) with galactorrhea only two days after a new two day course of metoclopramide. The drug was withdrawn and within days mastodynia and galactorrhea subsided. A control of plasmatic prolactin two weeks later yielded a normal value (358 microU/l). After administration of metoclopramide or domperidone hyperprolactinemia is regularly observed and galactorrhea has been described earlier. It is unclear why this patient inspite of repeated administration of one dopamine antagonist remained asymptomatic whereas the other after a short time and only a few doses led to galactorrhea. It is conceivable that differences in passage into the cerebrospinal fluid or the better penetration of the blood-brain barrier favored the development of galactorrhea under metoclopramide. This case served to discuss the pathophysiologic background of drug-induced hyperprolactinemia.

Adult↗
PubMed1992

[Clinical-pharmacological case report: drug-induced inappropriate ADH secretion].

The syndrome of inadequate secretion of antidiuretic hormone (SIADH) following treatment with a tricyclic antidepressant is demonstrated using the example of a 70 year-old man admitted for weakness and cognitive disturbances. Because of incontinence he had been periodically treated since 1989 with imipramine (Tofranil) by his family doctor. On admission he was seriously hyponatriemic and had low plasmatic osmolality, significantly lower than urinary osmolality. Creatinine, urea and uric acid in serum were also below normal values. Like other drugs tricyclic antidepressants can rarely induce an increased release of ADH by direct hypothalamic stimuli. In this patient imipramine was terminated and within a few days of reduced fluid intake and substitution of sodium a sustained clinical improvement and normalisation of laboratory parameters was noted. The patient was discharged to his home after three weeks.

Aged↗
PubMed1992

Implications of pulsatile stretch on growth of saphenous vein and mammary artery smooth muscle.

Internal mammary artery (IMA) coronary bypass grafts have a higher patency than saphenous vein (SV) grafts. Intimal hyperplasia and occlusion of venous grafts result from smooth muscle proliferation. Mechanical factors, such as pulsatile stretch, are potential mediators of this process. Smooth muscle cells from IMA and SV were cultured on deformable membranes and exposed to pulsatile stretch (60 cycles/min). This stimulus increased 3H-thymidine incorporation into venous (a two-fold increase) but not arterial smooth muscle cells after 24 h. Smooth muscle cell numbers from SV, but not IMA, were increased (p less than 0.05) after 6 days of stretch. Thus, pulsatile stretch stimulates smooth muscle cell proliferation in SV, but not IMA, and may contribute to venous bypass graft disease.

Cell Division↗
PubMed1992

[Transesophageal echocardiography: technique, indications and findings].

The introduction of transesophageal echocardiography (TEE) as a 'semi-invasive' technique with few complications in clinical practice represents a major diagnostic advance in the evaluation of cardiac disease. The close anatomic vicinity of the transducer to the heart and thoracic aorta allows the use of high frequency devices with better resolution compared to transthoracic echocardiography. Furthermore, the diagnostic gain when evaluating structures that are poorly visualized by the transthoracic approach such as the left atrial appendage, interatrial septum, prosthetic valves and the thoracic aorta is highly improved by TEE. Major indications for TEE include the search for a cardiac source of embolism and cardiac tumors, the work-up prior to balloon mitral valvuloplasty, the evaluation of prosthetic valves and the search for vegetations and aortic dissection. After a short summary of patient preparation, instrumentation and examination technique, the major indications, contraindications and complications are reviewed on the basis of our own experience and the literature.

Aortic Dissection↗
PubMed1992

[Endothelin-induced vasoconstriction in man: variable modification caused by endothelium-derived relaxing factor, Sodium nitroprusside and calcium antagonists].

The vascular effects of endothelin-1 (ET) were investigated in 25 healthy volunteers by measuring changes of forearm blood flow in response to brachial artery ET infusions. ET in a low dose (0.5 ng/min/100 ml tissue) resulted in a small but significant increase of forearm blood flow (FBF) from 2.3 +/- 1.5 to 2.5 +/- 1.5 ml/min/100 ml (n = 25, p less than 0.05) while higher dosages (25 and 50 ng/min/100 ml) resulted in significant decreases of FBF to 1.78 +/- 1.3 and 1.1 +/- 0.9 ml/min/100 ml (p less than 0.01). Neither sodium nitroprussid (n = 6) nor acetylcholine (n = 7) prevented ET-induced vasoconstriction. In contrast, both verapamil (n = 6) and nifedipine (n = 6) not only prevented ET-induced vasoconstriction but resulted in additional vasodilatation to values above those seen with the calcium antagonists alone. Thus, in human resistance vessels ET has a dual action with vasodilation occurring at low dosages and vasoconstriction at high dosages. Blockade of voltage-operated calcium channels prevents ET-induced vasoconstriction and unmasks the vasodilatory effects of high ET-dosages. Blockade of voltage-operated calcium channels but not cyclic GMP dependent vasodilation appears to be an effective tool in preventing ET-induced vasoconstriction.

Acetylcholine↗
PubMed1992

Intraluminal pressure modulates vascular contractility of perfused mesenteric resistance arteries. Altered response in hypertension.

Intraluminal pressure may affect vascular contractility in both normotension and hypertension. To test this hypothesis, we studied mesenteric resistance arteries from normotensive humans as well as normotensive (WKY) and spontaneously hypertensive (SHR) rats (internal diameter 214 +/- 27, 201 +/- 6, and 172 +/- 6 microns, mean +/- SEM at 10 mm Hg). Vessels were mounted on glass cannulas and perfused in organ chambers filled with buffer solution at intraluminal pressures of 10 to 120 mm Hg; vasomotion was measured using a video dimension analyzer. Under baseline conditions (10 mm Hg), wall thickness was 36 +/- 4 microns in humans, 32 +/- 4 microns in WKY, and 47 +/- 2 microns in SHR (P less than .001). With increasing pressure, the diameter of human vessels increased up to 25 mm Hg and remained constant at higher pressures. In contrast, resistance arteries of normotensive and hypertensive rats exhibited an almost linear increase in diameter over the whole pressure range. In SHR, the pressure-diameter relationship was much flatter than that of WKY, indicating reduced compliance. In human arteries, the contraction to KCl was maximal at 25 mm Hg and averaged 40 +/- 6%. Both above and below 25 mm Hg, the response declined to a minimum of 17 +/- 2% at 120 mm Hg (P less than .01). Similar results were obtained in WKY rats. In contrast, the contractile response in SHR remained maximal over the entire pressure range studied (65 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Heterogeneity of endothelial dysfunction in hypertension.

The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.

Animals↗
PubMed1992

Endogenous and exogenous nitrates and their role in myocardial ischaemia.

1. Although nitrates have been prescribed in patients with angina pectoris for more than a century, their mechanism of action has only been understood recently. 2. The discovery of the endogenous nitrovasodilator nitric oxide, which is formed in endothelial cells by the enzyme nitric oxide synthase, has greatly expanded our knowledge. Nitric oxide, if released from endothelial cells can interact with vascular smooth muscle as well as circulating blood cells such as platelets. Nitric oxide activates soluble guanylate cyclase, which in turn leads to an intracellular increase in cyclic GMP. In vascular smooth muscle, this causes vasorelaxation, in platelets dysaggregation and prevention of platelet adhesion. This protective pathway both reduces the effects of vasoconstrictor substances, can produce profound vasodilation, if activated appropriately and acts as a regulator of platelet-vessel wall interaction. In addition, nitric oxide inhibits the production and action of endothelin, a 21 amino acid vasoconstrictor peptide formed by endothelial cells. 3. Exogenous nitrovasodilators also exert their action by releasing nitric oxide from the molecule. Their action is particularly pronounced in blood vessels with a low basal production of nitric oxide and is enhanced after removal of the endothelium. In coronary artery disease, the formation of endothelium-derived nitric oxide is reduced, its breakdown is increased, but only at later stages, is the action of endogenous and therapeutic nitrates depressed. 4. Hence, nitrates are an appropriate therapeutic tool in patients with coronary artery disease to substitute the effects of the impaired activity of the endothelial L-arginine/nitric oxide pathway.

Coronary Disease↗
PubMed1992

Age, hypertension and hypercholesterolaemia alter endothelium-dependent vascular regulation.

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension and hypercholesterolaemia. All three conditions are associated with a decreased basal and simulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of a cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The circulating levels of endothelin-1 on the other hand are not increased in experimental and human hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduced endothelium-dependent relaxations to aggregating platelets, serotonin and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension and hypercholesterolaemia may have important clinical implications for the pathogenesis of cardiovascular disease.

Aging↗
PubMed1992

Endothelium-derived contracting factors.

The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase-dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation.

Endothelins↗
PubMed1992

Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries.

In cultured endothelial cells, endothelin is produced after stimulation with angiotensin II. The effects of angiotensin II and endothelin-1 on vascular sensitivity to norepinephrine were studied in perfused rat mesenteric resistance arteries. Expression of endothelin messenger RNA (mRNA) was determined in endothelial cells obtained from the mesenteric circulation. Perfusion (5 hours) of the arteries with angiotensin II (10(-7) M) potentiated contractions in arteries with endothelium induced by norepinephrine in spontaneously hypertensive rats but not Wistar-Kyoto rats. The potentiation was inhibited by phosphoramidon and an endothelin antibody. Short-term stimulation (1 hour) with angiotensin II did not cause the potentiation. Stimulation with angiotensin I (10(-7) M; 5 hours) caused a potentiation prevented by captopril. In endothelial cells collected from the mesenteric arterial bed of spontaneously hypertensive rats, endothelin-specific mRNA was constitutively expressed, and the level of endothelin transcripts was increased by angiotensin II (10(-7) M). Threshold concentrations of exogenous endothelin-1 potentiated contractions induced by norepinephrine in arteries with and without endothelium of spontaneously hypertensive rats but not Wistar-Kyoto rats. Thus, angiotensin II stimulates the endothelial production of endothelin in situ and therapy potentiates contractions to norepinephrine in mesenteric resistance arteries of spontaneously hypertensive rats. This suggests that vascular endothelin production acts as an amplifier of the pressor effects of the renin-angiotensin system that may play an important role in hypertension.

Angiotensin I↗
PubMed1992

Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium.

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelium evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10(-5) M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.

Acetylation↗
PubMed1992

Endothelin: systemic arterial and pulmonary effects of a new peptide with potent biologic properties.

Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. In vascular smooth muscle, endothelin binds to a specific receptor (ETA-subtype), which activates phospholipase C, leads to the formation of inositol trisphosphate, diacylglycerol (which activates protein kinase C), and increased intracellular Ca2+. In certain blood vessels, the endothelin receptor on vascular smooth muscle is linked to a voltage-operated Ca2+ channel via a G-protein. This explains why Ca2+ antagonists inhibit endothelin-induced contractions in certain, but not all, blood vessels. In the human forearm circulation, Ca2+ antagonists do prevent endothelin-induced contractions and unmask endothelin-induced vasodilation mediated by endothelial prostacyclin production (via the ETB-receptor). The pulmonary circulation plays an important role in the metabolism of endothelin, as the lungs take up large quantities of the peptide during passage. Endothelin has profound vasoconstrictor effects in the pulmonary circulation (and also in bronchial tissue), and its production is augmented in pulmonary hypertension. In systemic hypertension, the circulating endothelin levels appear to be normal. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are increased. Thus, endothelin is a potent mediator in the systemic and pulmonary circulation and, in particular, in diseases of the vasculature.

Animals↗
PubMed1992

Chronic cyclosporine therapy impairs endothelium-dependent relaxation in the renal artery of the rat.

Cyclosporine is an immunosuppressive substance that causes structural and functional alterations in endothelial cells. To examine the effects of chronic cyclosporine therapy on endothelial function, Wistar Kyoto rats received daily s.c. injections of saline, cyclosporine solvent, or cyclosporine (15, 30, or 50 mg/kg) for up to 2 wk. Blood pressure remained unchanged in all groups. Segments of the renal artery were suspended in organ chambers filled with physiological salt solution, and isometric tension was recorded. In rats treated with 30 or 50 mg/kg/day of cyclosporine, endothelium-dependent relaxations to acetylcholine of the renal artery were significantly impaired when compared with vessels obtained from rats injected with saline or solvent. The reduced acetylcholine-induced relaxation of cyclosporine-treated vessels was improved by preincubation of the preparations with the cyclooxygenase inhibitor indomethacin. Endothelium-independent relaxations in response to sodium nitroprusside were unimpaired in renal artery rings after 1 wk of cyclosporine but were reduced after 2 wk of treatment with 30 mg/kg/day. Contractions of the renal artery in response to norepinephrine and serotonin were not altered by cyclosporine. Thus, (1) high-dose cyclosporine therapy impairs endothelium-dependent relaxations in the renal artery of the rat; (2) an endothelium-derived cyclooxygenase product reduces the effects of endothelium-derived relaxing factor in cyclosporine-treated rats; and (3) chronic cyclosporine treatment slightly impairs vascular smooth muscle relaxation, whereas vascular contractility remains unaltered.

Acetylcholine↗
PubMed1992

Endothelin-induced vasoconstriction and calcium antagonists.

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide, is one of the most potent of these factors, which can control local vascular tone. The peptide is formed from its precursor, big endothelin, via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1 and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to its specific receptor (ETA-receptor and possibly ETB-receptor) which activate phospholipase C and lead to the formation of inositol trisphosphate, diacylglycerol and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to voltage-operated calcium channels via a Gi-protein. This linkage may explain why calcium antagonists inhibit endothelin-induced contractions in certain, but not other blood vessels. In large conduit arteries, such as the human internal mammary artery, endothelin-induced contractions are primarily mediated by release of intracellular calcium and hence, calcium antagonists do not markedly affect the response. In contrast, in the human forearm circulation, calcium antagonists of different classes do prevent endothelin-induced contractions. Similarly, in mesenteric resistance arteries of the rat, calcium antagonists can reverse endothelin-induced contraction suggesting that calcium antagonists are particularly potent in inhibiting endothelin-induced contraction in resistance arteries, where peripheral vascular resistance and hence, blood pressure is regulated.

Animals↗
PubMed1992

Endothelium-dependent regulation of resistance arteries: alterations with aging and hypertension.

Small arteries with a diameter of 200 microns or less play an important role in the regulation of peripheral vascular resistance. Dysregulation of vascular tone of these arteries may contribute significantly to high blood pressure. The contractile state of blood vessels is regulated by peripheral neurons, vascular smooth muscle, and the endothelium. In perfused mesenteric resistance arteries of the rat, removal of the endothelium markedly augments the sensitivity and maximal response to norepinephrine and endothelin-1. Acetylcholine causes profound endothelium-dependent relaxation of resistance arteries contracted with norepinephrine or endothelin-1. The potency of the muscarinic agonist is particularly pronounced with intraluminal application. The inhibitory effects of the endothelium against contractions induced by norepinephrine and endothelin-1 are reduced with aging and hypertension. The endothelium-dependent relaxation in response to intraluminal, but not extraluminal, acetylcholine is blunted in mesenteric resistance arteries of hypertensive rats and in the forearm circulation of hypertensive patients studied in vivo. The sensitivity of vascular smooth muscle to the effects of endothelin decreases with advancing age and in the spontaneously hypertensive rat. Thus, endothelium-derived vasoactive substances can profoundly affect vascular tone of resistance arteries studied in vitro and in vivo. The inhibitory effects of the endothelium against vasoconstrictor stimuli decreases with aging and hypertension, indicating a dysfunction of these regulatory mechanisms under these conditions.

Aging↗