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Biomedical subjects

T Gräser

Publications and source records attributed to T Gräser.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effect of cilazapril and indomethacin on endothelial dysfunction in the aortas of spontaneously hypertensive rats.

Chronic hypertension is associated with impaired endothelial function [i.e., reduced synthesis/release of endothelium-derived relaxing factor (EDRF) and increased synthesis/release of endothelium-derived contracting factor (EDCF)] in both animals and humans. Although it is not known whether endothelial dysfunction is the consequence and/or an important pathogenetic cause of hypertension, the goal of effective antihypertensive therapy should include restoration of normal endothelial function as well. Because angiotensin I-converting enzyme (ACE) inhibitors are effectively used in the treatment of hypertension, the aim of the present study was to test whether in vivo treatment of spontaneously hypertensive rats (SHRs) with the ACE inhibitor cilazapril improves endothelial function in the isolated thoracic aorta of SHRs. Treatment of SHRs with cilazapril (10 mg/kg/day orally for 2 weeks) resulted in a significant decrease in blood pressure and normalization of endothelium-dependent relaxation evoked by acetylcholine (ACh) and adenosine diphosphate (ADP). However, cilazapril treatment had no significant effect on endothelium-dependent contractions evoked by 5-hydroxytryptamine (5-HT; serotonin) and prostaglandin F2 alpha (PGF2 alpha). In contrast, in vitro treatment of isolated thoracic aortas with indomethacin (10(-5) M) normalized endothelium-dependent relaxations to ACh and ADP as well as inhibited endothelium-dependent contractions to 5-HT and PGF2 alpha. These results suggest that the ACE inhibitor cilazapril increases the synthesis/release of EDRFs whereas indomethacin prevents the synthesis/release of cyclo-oxygenase-derived EDCFs in the endothelium of rat aorta. The exact mechanism of action of ACE inhibitors on endothelial dysfunction remains to be determined.

Acetylcholine↗
PubMed1991

Hypoxic contraction in canine basilar arteries: role of endothelium.

The effect was studied of severe hypoxia (partial pressure of oxygen below 20 mm Hg) on the tone of isolated canine basilar arterial rings with and without endothelium. Short-lasting exposure (8 min) to hypoxia induced a pronounced contraction that did not differ in vessels with and without endothelium. The hypoxia-induced changes of vessel tone were reproducible in 3 consecutive episodes of hypoxia interspaced by 45 min of control oxygenation. Reintroduction of oxygen induced a posthypnoxic relaxation in preparations without endothelium and a posthypoxic contraction in part (5 of 15) of the arteries with endothelium. The hypoxic contraction was not influenced by the cyclooxygenase inhibitor indomethacin and the thromboxane A2 receptor antagonist BM 13.505 while the posthypoxic response was diminished by both inhibitors. The Ca(++)-entry blocker D600 abolished both hypoxic and posthypoxic contractions completely.

Animals↗
PubMed1991

Hypoxic contraction of canine coronary arteries: role of endothelium and cGMP.

The effect of severe hypoxia in quiescent or contracted (prostaglandin F2 alpha) canine coronary artery rings with and without endothelium was studied. Hypoxia induced an initial transient relaxation followed by a sustained contraction. The hypoxic contraction in quiescent rings was comparable in rings with and without endothelium. The facilitation of the contraction to prostaglandin F2 alpha was more pronounced in rings with endothelium. Increasing the level of contractions by augmenting the contraction of prostaglandin F2 alpha potentiated the hypoxic contraction in rings with endothelium only. Methylene blue, LY 83583, and nitro-L-arginine reversed the hypoxic facilitation in contracted rings into relaxation, whereas M&B 22948 augmented it. In quiescent coronary preparations, methylene blue reversed the hypoxic contraction into relaxation in preparations with and without endothelium, whereas nitro-L-arginine had the same effect in vessels with endothelium only. SIN-1, nitroglycerin, and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) unmasked hypoxic facilitation in rings without endothelium. This was not observed with isoproterenol. The measurement of the level of cGMP revealed an increased level in rings with endothelium compared with those without endothelium under control oxygenation. This difference disappeared during hypoxia due to a decrease of cGMP content in vessels with endothelium. The results suggest that a moderate increase of the cGMP level in vascular smooth muscle is a prerequisite for the occurrence of hypoxia-induced facilitation in contracted canine coronary arteries.

Animals↗
PubMed1991

Endothelium-dependent contractions.

The endothelial cells help to control the tone of the underlying vascular smooth muscle by releasing vasoactive factors. In physiological circumstances, the release of relaxing factors (nitric oxide and endothelium-derived hyperpolarizing factor) appears to predominate. However, in certain blood vessels (peripheral veins and large cerebral arteries), the normal endothelium has the propensity to release vasoconstrictor substances, among which are superoxide anion and thromboxane A2; the release of these endothelium-derived vasoconstrictors may contribute to the autoregulatory processes. In most blood vessels, anoxic conditions initiate the release of an unidentified endothelium-dependent contracting factor. Cultured endothelial cells, and blood vessels maintained under culture conditions for prolonged periods of time, release the vasoconstrictor peptide endothelin. A characteristic of vascular diseases is that the ability of the endothelial cells to release relaxing factor(s) is reduced, while the generation of contracting factor is maintained or enhanced.

Animals↗
PubMed1991

Effect of hypoxia on endothelium-dependent relaxation of porcine coronary arteries and veins.

In isolated transverse strips of porcine coronary artery and rings of coronary vein both mild (pO2 = 70 +/- 2.6 mmHg) and severe (pO2 = 17.4 +/- 0.8 mmHg) hypoxia (30 min duration) produced a transient contraction depending on the severity of hypoxia. Hypoxia did not influence the contraction evoked by prostaglandin F2 alpha in coronary veins but inhibited it significantly in coronary arteries. In the venous preparations there was no change of the endothelium-dependent relaxation to bradykinin and acetylcholine during mild hypoxia but these responses were inhibited during exposure to severe hypoxia. The endothelium-dependent relaxation to bradykinin produced in coronary arteries was not modified by mild hypoxia but was inhibited in the higher concentration range of bradykinin by severe hypoxia. The results suggest a higher sensitivity of porcine coronary arteries to hypoxia compared to coronary veins that could be due to the different morphology (thickness) of the vessel wall. This may play a role in pathophysiology including hypoxic state during coronary vasospasm.

Acetylcholine↗
PubMed1990

Study on the mechanism of carbon monoxide induced endothelium-independent relaxation in porcine coronary artery and vein.

In superfusion experiments on isolated porcine coronary arterial and venous ring preparations precontracted by prostaglandin F2 alpha repeated bolus application of carbon monoxide induced a reproducible relaxation. The vessels were rubbed to remove the endothelium, 30 min superfusion with 10(-5) M of 8-bromocyclic-GMP decreased the tension in coronary artery and vein and reduced the carbon monoxide response in the latter. Methylene blue increased the tone and inhibited the carbon monoxide effect in both vessels. The results show that carbon monoxide relaxing action on vascular smooth muscle might be due to activation of guanylate cyclase similar to the action on nitric oxide and/or endothelium-derived relaxing factor.

Animals↗
PubMed1990

Hypoxic and posthypoxic responses in isolated coronary arteries and veins: role of endothelium.

In isolated porcine and canine coronary artery and vein short-lasting exposure (8 min) to hypoxia (pO2 less than 20 mm Hg) evoked an increase of tone (6-34% of maximum contraction to potassium chloride). In arterial preparations of both species this response was significantly more pronounced in endothelium-intact vessels as compared to rubbed ones. Reintroduction of oxygen produced a posthypoxic dilation in coronary artery and a posthypoxic contraction in coronary vein. The latter was significantly higher in intact veins of the pig compared to the rubbed preparation but did not differ in canine veins. Repeated exposure to hypoxia with 1 h intervals of rest evoked mostly increased hypoxic and posthypoxic responses. The time of onset of hypoxic contraction was significantly shorter in intact canine coronary artery as compared to the rubbed preparation. The effects of indomethacin (inhibitor of cyclooxygenase), BM 13,505 (thromboxane A2 receptor antagonist) and D 600 (calcium entry blocker) differed in dependence on the response, the vessel and the species tested. Hypoxic contraction in canine coronary artery seems to be more sensitive to blockade of calcium entry whereas hypoxic contraction in porcine coronary artery and hypoxic contraction and posthypoxic contraction in coronary vein of both species are less sensitive to external calcium entry and probably mediated by products of the cyclooxygenase pathway of arachidonic acid. It is suggested that hypoxic and posthypoxic contraction might play a role in redistribution of blood flow from hypoxic to normoxic tissue of the heart during ischemia.

Animals↗
PubMed1990

Effect of human recombinant interleukin-2 on isolated rabbit femoral artery and porcine coronary artery and vein.

Treatment of cancer patients with disseminating malignancy using human recombinant interleukin-2 (rIL-2) is usually complicated by some adverse effects such as hypotension, an increase in vascular permeability and water retention due to the so-called "capillary leak syndrome". Experiments on isolated vessels were carried out to study whether rIL-2 has some direct and/or endothelium-mediated influence upon smooth muscle tone. RIL-2 produced a slight insignificant increase in tension in both intact (E+) and endothelium-denuded (E-) rabbit femoral artery (RFA) rings which was more pronounced in E-rings. No direct or endothelium-mediated relaxation of RFA smooth muscle was observed. Endothelium-dependent relaxation induced by acetylcholine was not inhibited as well. RIL-2 produced equal relaxation in E+ and E- porcine coronary artery (CA) and coronary vein (CV). The relaxing effect was more pronounced in CA than in CV. The rIL-2-induced inhibitory effect on coronary vessels does not depend on endothelium, and its mechanism is not clear until now.

Acetylcholine↗
PubMed1989

Superoxide dismutase does not improve penetration of endothelium-derived relaxing factor (EDRF) through the vessel wall.

In superfusion bioassay systems including rabbit aorta donor segment, femoral artery detector rings and porcine circumflex coronary artery donor segment, interventricular coronary artery detector rings, the transwall movement of EDRF was tested. No penetration of the factor through the vessel wall could be detected even after stabilization of EDRF by superoxide dismutase whereas a pronounced relaxation of recipient vessels on intraluminally released EDRF could be seen.

Acetylcholine↗
PubMed1988

A new method for removal of vascular endothelium by saponin in isolated porcine coronary artery and rat aorta.

Saponin was used to remove endothelium in isolated porcine coronary artery strip and rat thoracic aorta ring preparations. Endothelium-dependent relaxations of precontracted vessels induced by bradykinin in porcine coronary artery, and by acetylcholine in rat aorta were completely abolished on treatment with saponin (100 micrograms/ml, 5-10 min). In the porcine vessel, contractile responses to prostaglandin F2 alpha did not change, while in the rat aorta those to norepinephrine even increased. Compared to mechanical removal of endothelium, the method used may be easily standardized, and is especially suited for small resistance vessels.

Acetylcholine↗
PubMed1988

[The influence of preload on the reactivity of coronary arteries].

Usually, blood vessel preparations used for in vitro investigations are kept under a certain passive preload. This preload influences the blood vessel reactivity against agonists. Using transverse strips of porcine coronary arteries (Ramus circumflexus) the influence of preload on the amplitude of blood vessel responses induced by acetylcholine, potassium ions and prostaglandin F2 alpha was tested. The optimum preload to obtain a maximum contraction was 1.92 +/- 0.14 g. This value did neither depend on the agonist nor its concentration. However, there was a direct relation between the size of the vessel preparation and the value of the optimum preload. Thus, it is worth taking into account the correct preload when blood vessel preparations are tested in vitro.

Acetylcholine↗
PubMed1988

Vasomotor tone of isolated porcine coronary veins in response to acetylcholine, noradrenaline, and histamine.

The reactivity of isolated porcine coronary venous segments to acetylcholine, noradrenaline, and histamine was tested in organ bath experiments. Acetylcholine dilated precontracted venous preparations endothelium-dependently. This relaxation was inhibited by atropine indicating the muscarinic nature of this response. Noradrenaline contracted the vessels by an alpha-adrenergic mechanism, whereas beta-receptor-induced dilatation could not be seen. Histamine induced contraction of porcine venous preparations via H1-receptors. These results suggest that the coronary venous system is involved in the regulation of the coronary blood flow in addition to metabolic mechanisms and to nervous influences on the arterial side.

Acetylcholine↗
PubMed1987

Coronary smooth muscle reactivity to repeated agonist administration in a long-time experiment in vitro.

The reactivity of isolated extramural coronary arteries of the pig to repeated agonist administration (acetylcholine, prostaglandin F2 alpha and K+-contraction) was investigated in a long-time experiment (20 h, more than 60 reactions). The acetylcholine-evoked contractions show an amplitude increase (phasic component) during the first 10 responses followed by approximately 20 constant reactions and a final amplitude decrease with alternative changes in amplitude. The tonic component of the acetylcholine responses decreases uniformly. The amplitude of K+-contraction increases during the first 10 reactions, and remains nearly constant in the further experiment. Prostaglandin F2 alpha produces a maximum contraction already in its first response, but the amplitudes decrease considerably after 6-8 reactions. The time course of the corresponding contraction upstroke velocity is quite similar compared to the amplitude behaviour. Differences in the smooth muscle reactivity between the used agonists are explained by different activatory mechanisms. Some hints concerning an optimum experimental procedure are given.

Acetylcholine↗
PubMed1987

The action of acetylcholine on isolated coronary arteries of different species.

The action of acetylcholine (ACh) on extramural coronary arteries (CA) of dogs, pigs, and humans was tested in vitro. ACh dilated precontracted canine CA in dependence on the state of endothelium. This dilation was mediated through muscarinic receptors since atropine inhibited it effectively. Preparations without active precontraction were not influenced at all or slightly dilated. Both human and porcine CA were exclusively contracted by ACh independently of the presence or absence of precontraction. The ACh contraction in porcine CA was found to be endothelium-independent, but also inhibited by atropine as well as the ACh contraction in human CA. Adrenoceptor blockers did not influence ACh reactivity. High concentrations of ACh (greater than 10(-5) mol/l) decreased the further responsiveness of the vessels to the mediator (tested in dogs and pigs only). Spontaneous mechanical activity was registered only in human CA. Different ACh reactivity in dogs compared with pigs and humans is interpreted as species-dependent. It must be taken into account when human coronary physiology is modeled in animals.

Acetylcholine↗
PubMed1986

Absence of role of endothelium in the response of isolated porcine coronary arteries to acetylcholine.

Isolated precontracted arteries of various vascular beds relax in response to acetylcholine only if the endothelium is present. One explanation for this is that this drug stimulates the endothelial cells to release a vasodilator substance that in turn relaxes the underlying smooth muscle. To determine whether this mechanism is concerned also in the acetylcholine contraction of isolated porcine coronary arteries transverse strips of the extramural part of the left circumflex artery were used for recording isometric tension in the muscle bath. Dose-response curves for acetylcholine showed no significant difference before and after removal of endothelium. As a functional check on the removal of endothelium, the responsiveness of each preparation to a known endothelium dependent dilator (substance P) was tested before and after removal. These findings suggest that endothelial cells are not concerned in the acetylcholine induced contraction of porcine coronary arteries. Acetylcholine appears to act directly on smooth muscle of the porcine artery.

Acetylcholine↗
PubMed1986

[Clinical interpretation of retinal circulatory measurements. III. Blood flow velocity and vessel diameter in normal persons and in patients with venous occlusive diseases].

Based on results from measurements of arterial blood velocity, arterial and venous diameters of major segmental retinal vessels in normal persons and in patients with venous occlusive diseases and in continuation of the two preceding parts of this series of articles, further possibilities for the differential diagnosis of measurements of retinal microcirculation magnitudes are discussed. Whereas the measurement of blood velocity is an important criterion for the assessment of the stasis conditions and the arterial involvement in an occlusive disease, the diameters of the vessels offer essential suggestions to local regulative processes. In this connection, a dependence on pH of the contraction state of the smooth vascular musculature detected in porcine coronary arteries is presented. By its transmission to the arterial retinal vessels, it is possible to unequivocally clarify the local regulative and pathological behavior of arterial retinal vessels in terms of flow physiology.

Blood Flow Velocity↗
PubMedDate not supplied

Is there an abluminal release of endothelium-derived relaxing factor (EDRF)?

In superfusion bioassay systems of rabbit thoracic aorta and femoral artery ring segments as well as canine femoral artery and coronary ring segments the release of endothelium-derived relaxing factor (EDRF) was stimulated by acetylcholine in donor segments with intact endothelium. The transition of EDRF through the vessel wall ("abluminal release") was not revealed in both bioassay systems. Externally applied acetylcholine did not reach the luminal surface of rabbit thoracic aorta but induced EDRF release in canine femoral artery segments.

Acetylcholine↗