PubMed Health⌕ Search

Biomedical subjects

U Pohl

Publications and source records attributed to U Pohl.

At least 91 records · Page 5Linked to original sources
PubMed1989

EDRF increases cyclic GMP in platelets during passage through the coronary vascular bed.

It was investigated whether endothelium-derived relaxing factor (EDRF) increases cyclic GMP (cGMP) content in platelets passing through the coronary bed. Boluses of washed platelets from healthy human donors were injected into the aortic perfusion line of isolated, saline-perfused rabbit hearts under constant flow conditions (28 +/- 2 ml/min). The coronary effluent was collected over 5 seconds, and the cGMP content of platelets was determined by radioimmunoassay. Platelet cGMP amounted to 0.34 +/- 0.11 pmol/mg protein after passage through the unstimulated coronary bed. During stimulation with acetylcholine (1 microM), it increased to 1.6 +/- 0.5 pmol/mg (p less than 0.01; n = 14). Simultaneously, the platelet recovery (measured over 20 seconds after injection) was enhanced (by 45 +/- 11%; p less than 0.01) during endothelial stimulation with acetylcholine. Treatment with the EDRF inhibitor hemoglobin (6 microM) completely abolished the increase in platelet cGMP (p less than 0.01; n = 11) as well as the enhanced platelet recovery (n = 8). Inhibition of EDRF by hemoglobin reduced also the basal platelet cGMP content to 0.17 +/- 0.11 pmol/mg (p less than 0.01). The data indicate that basally released EDRF is able to increase cGMP in platelets during a single passage through the coronary bed. The enhanced recovery of platelets after EDRF stimulation, which coincides with an increase of platelet cGMP, suggests that EDRF plays an important role as inhibitor of platelet activation in the coronary circulation.

Acetylcholine↗
PubMed1989

[The effect of carbon dioxide baths on blood pressure of borderline hypertensive patients].

In 423 patients with borderline hypertension (at rest and/or during exercise) the potential blood pressure reducing effect of CO2-baths was studied. Using standardized blood pressure measurements at rest and during exercise, it was investigated to what extent a fourweek course of CO2-baths could induce a reduction of blood pressure in these patients. They were randomly assigned to a course of baths with either high or low CO2-concentration. A significant fall in blood pressure, both at rest and during exercise was observed in both groups during the course of treatment. Multiple regression analysis identified the loss in body weight during treatment as the main influence factor on reduction in blood pressure. By contrast, no (additional) specific therapeutic effect of CO2-baths on blood pressure reduction could be observed.

Adult↗
PubMed1989

[Inhibition of thrombocyte aggregation and adhesion by endothelium-derived relaxant factor (EDRF) and their pathophysiologic significance].

Changes in viscous drag acting upon the endothelial lining and a number of circulating agonists (ATP, ADP, serotonin, thrombin) stimulate the release of EDRF from intact endothelial cells. EDRF is probably identical with nitric oxide (NO), the vasoactive compound which is also formed in the metabolism of nitrovasodilators in the vasculature (some of them directly release NO without the essential foregoing bioconversion step). Albuminally released NO stimulates soluble guanylate cyclase (sGC) in the vasculature initiating vasodilation; luminally released NO stimulates, sGC in platelets and increases cyclic GMP inhibiting platelet activation and aggregation. Endothelial impairment brings about loss of dilator and antiaggregant capacity.

Animals↗
PubMed1989

Mechanisms controlling the production of endothelial autacoids.

The endothelium plays an important role in the control of vascular tone and platelet activity. This is mainly achieved by the release of autacoids, particularly EDRF (identical with nitric oxide, NO) and PGI2. The release of both autacoids is evoked by physical factors like hypoxia and shear stress and by various chemical compounds like acetylcholine, ATP and bradykinin. These agonists bind to membrane receptors coupled to phospholipase C, thereby increasing production of inositol-1,4,5-trisphosphate (IP3). IP3 mobilizes Ca2+ from intracellular stores, thus elevating the intracellular free calcium concentration ([Ca2+]i), in synergy with a simultaneously induced transmembrane Ca2+ influx. The level of [Ca2+]i closely correlates with endothelial production of PGI2 whereas Ca2+ influx is apparently a decisive signal for the sustained release of EDRF. This influx may be facilitated by an agonist-induced membrane hyperpolarization probably being mediated by activation of Ca2+-dependent K+ channels. Depolarization of the endothelial cell membrane on the other hand (evoked by raising the extracellular K+ concentration) attenuates the Ca2+ influx as well as EDRF release. The agonist-induced endothelial hyperpolarization may also be electrotonically transmitted to adjacent smooth muscle cells via myoendothelial gap junctions and may act synergistically with the EDRF-mediated relaxation. Alternatively, spread of this electrical signal along the endothelial lining may enhance the release of autacoids.

Animals↗
PubMed1988

Fendiline and calmidazolium enhance the release of endothelium-derived relaxant factor and of prostacyclin from cultured endothelial cells.

We investigated the effects of fendiline, calmidazolium and trifluoperazine, compounds described as calmodulin antagonists, on the release of the endothelial autacoids prostacyclin (PGI2) and endothelium-derived relaxant factor (EDRF). Cultured bovine aortic endothelial cells were grown on microcarrier beads and continuously superfused with Tyrode's solution. Samples collected from the superfusate were assayed for PGI2 concentration (6-keto PGF1 alpha radioimmunoassay) and for EDRF activity (stimulation of soluble guanylate cyclase in vitro). Stimulation of endothelial cells by ATP (3 microM) resulted in a 6.9 +/- 1.4-fold increase of PGI2 concentration in the superfusate (p less than 0.01) and an 8.6 +/- 3.4-fold enhanced guanylate cyclase activity (p less than 0.01). In the presence of calmidazolium (10 microM), the basal values of PGI2 concentration increased 28-fold (p less than 0.01) and the guanylate cyclase activity 10-fold (p less than 0.01). Further enhancement of both was observed after additional administration of ATP. Fendiline (30 microM) did not affect autacoid release by non-stimulated cells. However, the ATP-induced release of PGI2 and EDRF was more than doubled (p less than 0.01) in the presence of this drug compared to ATP-stimulation alone. Trifluoperazine (10 microM) had no enhancing effect on EDRF release, and the ATP-induced release of PGI2 was even significantly attenuated by 84 +/- 12% (p less than 0.01). Calmidazolium and fendiline were also applied to endothelial cells loaded with the fluorescent indicator of free calcium concentration (Ca2i+), indo-1. However, effects of calmidazolium on Ca2i+ could not be quantified since calmidazolium caused some leakage of indo-1 out of the cells. A smaller leakage was observed during the combined application of fendiline and ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Treatment with natural human interferon alpha of a CML-patient with antibodies to recombinant interferon alpha-2b.

A patient with Philadelphia-chromosome positive chronic myelogenous leukemia developed interferon antibodies on treatment with recombinant interferon alpha-2b. Clinically this event corresponded with progressive disease. No cross-reactivity of antibodies with human leukocyte interferon was found by Western blot. Treatment was switched to human leukocyte interferon with an obvious clinical effect: WBC was reduced and platelet count stabilized, but the effect was transient and no hematologic remission was achieved. Human leukocyte interferon may be an alternative in CML-patients with neutralizing antibodies to recombinant interferon alpha.

Antibody Formation↗
PubMed1988

When should treatment of acute experimental pancreatitis be started? The early phase of bile-induced acute pancreatitis.

Sodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60 min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.

Acute Disease↗
PubMed1988

Differential role of extra- and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells.

1. The effects of extracellular Ca2+ on the release of endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), and on the intracellular free calcium concentration [( Ca2+]i), were studied in cultured bovine aortic endothelial cells. 2. Receptor-mediated stimulation of endothelial cells with bradykinin (10 nM) elicited a transient release of EDRF (assayed by its stimulant effect on purified soluble guanylate cyclase) and of PGI2 (measured by radioimmunoassay for 6-keto prostaglandin F1 alpha). 3. Bradykinin (10 nM) also increased [Ca2+]i (measured with the fluorescent probe indo-1) from 125 +/- 11 nM to 631 +/- 59 nM, with the same time course as for autacoid release. 4. In Ca2+-free medium, [Ca2+]i was still increased by bradykinin but declined faster (within 1 min) to resting levels than in the presence of extracellular Ca2+. 5. PGI2 release was almost completely abolished in Ca2+-free medium. The intracellular calcium antagonist TMB-8 evoked a similar inhibition of PGI2 release. 6. In contrast, bradykinin-induced EDRF release was not significantly affected by TMB-8 but was completely abolished in Ca2+-free medium. 7. When endothelial cells were stimulated with the receptor-independent drug thimerosal (an inhibitor of the enzyme acyl-CoA-lysolecithin-acyl-transferase; 5 microM), a long-lasting release of EDRF (greater than 90 min) and PGI2 (greater than 20 min) was observed. 8. In contrast to bradykinin stimulation, thimerosal-induced autacoid release was associated with only a slight increase of [Ca2+]i to 201 +/- 13 nM after 40 min. 9. After removal of extracellular Ca2 + from thimerosal-stimulated endothelial cells, [Ca2+] was little affected during the observation time of 90s. EDRF release was completely abolished within 90s whereas PGI2 release was unchanged. 10. We conclude that EDRF production is directly controlled by extracellular Ca2+ during both receptor-dependent and independent stimulation. This effect of extracellular Ca2 + is not mediated by changes in [Ca2+]i. In contrast, PGI2 release is closely correlated to [Ca2+]i in bradykininstimulated endothelial cells. However, the results obtained during thimerosal stimulation indicate that there is not necessarily a tight coupling between the absolute level of [Ca2+]i and the amount of PGI2 released. 9. After removal of extracellular Ca2 + from thimerosal-stimulated endothelial cells, [Ca2+] was little affected during the observation time of 90s. EDRF release was completely abolished within 90s whereas PGI2 release was unchanged. 10. We conclude that EDRF production is directly controlled by extracellular Ca2+ during both receptor-dependent and independent stimulation. This effect of extracellular Ca2 + is not mediated by changes in [Ca2+]i. In contrast, PGI2 release is closely correlated to [Ca2+]i in bradykininstimulated endothelial cells. However, the results obtained during thimerosal stimulation indicate that there is not necessarily a tight coupling between the absolute level of [Ca2+]i and the amount of PGI2 released. 9. After removal of extracellular Ca2 + from thimerosal-stimulated endothelial cells, [Ca2+] was little affected during the observation time of 90s. EDRF release was completely abolished within 90s whereas PGI2 release was unchanged. 10. We conclude that EDRF production is directly controlled by extracellular Ca2+ during both receptor-dependent and independent stimulation. This effect of extracellular Ca2 + is not mediated by changes in [Ca2+]i. In contrast, PGI2 release is closely correlated to [Ca2+]i in bradykininstimulated endothelial cells. However, the results obtained during thimerosal stimulation indicate that there is not necessarily a tight coupling between the absolute level of [Ca2+]i and the amount of PGI2 released.

Animals↗
PubMed1988

Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries.

Dinucleotides diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released from platelet-dense granules upon agonist-induced platelet aggregation. Since most platelet-derived compounds simultaneously affect aggregation and vascular tone, we investigated whether AP3A and AP4A have vasoactive properties. Experiments were performed in isolated, saline-perfused segments of rabbit mesenteric arteries precontracted with norepinephrine. In segments with intact endothelium, both dinucleotides (1-10 microM) induced vasodilation, with AP3A responses significantly greater. Vasodilator responses to AP3A in endothelium-denuded segments were not significantly different from those in segments with intact endothelium but those to AP4A in endothelium-intact segments were reversed to a pronounced contraction after endothelium removal. Likewise, pretreatment of endothelium-intact segments with gossypol (3 microM) reversed dilator responses to acetylcholine and to AP4A into contractions, whereas AP3A-induced dilation was not affected. In segments with intact endothelium but pretreated with reactive blue (10 microM), AP4A also induced a contraction. Dilator response to AP3A was not affected. High-performance liquid chromatographic analysis of effluent from vascular segments showed that neither AP3A nor AP4A was degraded during passage through segments. These results indicate that in rabbit mesenteric arteries both nucleotides act directly, and not through their hydrolysis products, on endothelial (AP4A) and/or smooth muscle receptors. The endothelium-dependent dilator effect of AP4A, is probably mediated by endothelial P2y-purinoceptors.

Acetylcholine↗
PubMed1988

Free radicals inhibit endothelium-dependent dilation in the coronary resistance bed.

Oxygen free radicals contribute significantly to ischemia-reperfusion myocardial damage in vivo. We studied the effect of reactive products of O2 generated by electrolysis of the saline perfusate on coronary vasomotor tone and endothelium-mediated vasodilator responsiveness in 41 isolated rabbit hearts. Under constant flow conditions, electrolysis induced a progressive increase in perfusion pressure associated with a modest reduction in myocardial contractile function. The responses to the endothelium-independent vasodilators papaverine and adenosine tended to be increased by 1.5- to 2-fold, indicating that the increase in perfusion pressure was due, at least in part, to increased resistance vessel tone. However, resistance vessel dilations to the endothelium-dependent agents acetylcholine and serotonin were markedly reduced. Various degrees of protection against increases in perfusion pressure and inhibition of endothelium-dependent dilation during electrolysis were obtained with catalase, a scavenger of hydrogen peroxide; superoxide dismutase, a scavenger of superoxide; and desferrioxamine, which chelates iron and thereby inhibits hydroxyl radical production. Furthermore the action of nitroprusside, a direct-acting stimulator of soluble guanylate cyclase, was not diminished during the electrolytic treatment. We conclude that inhibition of endothelium-dependent dilation is a prominent action of reactive products of O2 in the coronary resistance bed. In combination with a free radical-induced increase in resistance vessel tone this might limit recovery of myocardial perfusion post ischemia.

Acetylcholine↗
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

Influence of buprenorphine on acute experimental pancreatitis.

Buprenorphine (15 micrograms/kg b.wt. per hour) distinctly reduced pain sensitivity in acute 3% sodium-taurocholate pancreatitis in male Wistar rats without interfering with the course of the disease. This was seen by assessment of enzyme elevation in serum and ascites and by histological evaluation of the pancreas. Buprenorphine is therefore recommended for animal experiments to study the effect of therapeutic principles in acute pancreatitis.

Acute Disease↗
PubMed1987

Endothelium-derived relaxant factor inhibits effects of nitrocompounds in isolated arteries.

We investigated the influence of endothelial cells on the smooth muscle vasodilator effects to sodium nitroprusside (SNP) or Teopranitol (an organic mononitrate) in isolated segments of rabbit aorta and femoral artery. In the femoral artery, the vasodilator responses to both nitrocompounds were significantly higher in the absence of endothelial cells or after pretreatment with the endothelium-derived relaxant factor (EDRF) inhibitor nordihydroguaiaretic acid (NDGA; 10 microM). Moreover, under conditions of stimulated EDRF release (induced by acetylcholine; 30-100 nM) the vasodilator responses to SNP were further attenuated in vessels with intact endothelium. By contrast, in the rabbit aorta, the vasodilator responses to the nitrocompounds were not significantly altered by either endothelium removal or treatment with NDGA. However, in the presence of the EDRF stimulator acetylcholine, the dose-response curve to SNP was shifted to right in the aorta as well. The role of EDRF in the endothelium-mediated attenuation of the dilator potency of SNP was further investigated by using EDRF released from cultured (bovine aortic) endothelial cells. The dilator effects of SNP were compared in endothelium denuded femoral or aortic segments in the presence or absence of EDRF. The vasodilator effects of SNP in both types of arteries were significantly reduced in the presence of EDRF. We conclude that EDRF attenuates the arterial vasodilation induced by SNP and Teopranitol. The results further suggest that endothelial cells exhibit a greater basal release of EDRF in the femoral artery than in the aorta, since under unstimulated conditions an EDRF-induced attenuation was seen only in femoral and not in aortic segments.

Acetylcholine↗
PubMed1987

Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo.

In vivo experiments were performed in autoperfused hindlimbs of rabbits to investigate the role of endothelium-mediated vasomotion in resistance-sized vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP, and substance P (SP), all of which have been shown to act in an endothelium-dependent manner in large conduit arteries, were studied before and after exposure of the hindleg vasculature to gossypol (a potent inhibitor of endothelium-mediated vasodilation in vitro). The flow responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2 (PGE2), which induce relaxation by a direct effect on vascular smooth muscle, were tested in the same manner. All vasodilators induced dose-dependent increases in femoral flow up to two- to threefold when administered intra-arterially. After gossypol, the flow responses to the endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced (by 88 +/- 3%, P less than 0.01) or sometimes were converted to constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN remained largely unaffected. Sham treatment (gossypol solute only), exposure to indomethacin (10 microM), and ganglionic blockade had no differential effect on the flow responses. The selective action of gossypol in suppressing the flow responses to the endothelium-dependent compounds ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells in resistance-sized vessels in vivo.

Adrenergic beta-Antagonists↗
PubMed1987

Subcutaneous administration of the synthetic trypsin inhibitor Foy-305 induces hypertrophy of the exocrine pancreas.

The serine protease inhibitor camostate (Foy-305; 200 mg/kg body weight) had been administered twice daily either subcutaneously or orally to mice for 5, 10 and 15 days. Within 5 days, pancreatic weight, concentration of trypsin, amylase and protein were significantly increased and even more increased after 10 and 15 days. This effect is less pronounced after subcutaneous administration in comparison to oral treatment.

Administration, Oral↗
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↗