The endothelium-dependent relaxation of human middle cerebral artery: Effects of activated neutrophils

Neutrophils, activated by 4-phorbol-12-myristate-13-acetate, decreased acetylcholine-induced relaxation of strips of human middle cerebral artery precontracted with noradrenaline. This effect was prevented by catalase, but not by superoxide dismutase. Nifedipine, propranolol and, less markedly, captopril reduced the decrease in acetylcholine-induced relaxation. Aspirin and dipyridamole did not reduce it.     

Vasomotor escape from adrenaline,noradrenaline or acetylcholine in the dog hind limb

Summary The noradrenaline, adrenaline and acetylcholine-induced vasoregulatory escape was demonstrated in the vascular bed of intact or skinned and denervated dog's hind limb. Escape effect disappeared or decreased markedly under elevation tissue pressure in the examined hind limb. These data indicate that tissue pressure factor may take part in the mechanism of the escape phenomenon.     

Der Einfluss von Calcium auf die Brenzcatechinaminfreisetzung

Summary (1) Experiments on isolated perfused suprarenals of cattle have shown that the acetylcholine-induced release of catechol amines, but not that of phenylethylamine, is dependent on calcium, since a perfusion with calcium-free Tyrode's solution abolishes the action of acetylcholine and not that of phenylethylamine. (2) Inincubation experiments with isolated chromaffin granules, calcium produces a dose-dependent, significant release of catechol amines even in physiological concentrations (2.5 mM). (3) Acetylcholine does not release catechol amines from isolated granules, either in the presence or in the absence of calcium.

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Forschungs-Stipendiat der A. von Humboldt-Stiftung.

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Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Cholinergic components in the gastrin pathway of gastric acid stimulation

Summary In the isolated whole stomach of the mouse, cimetidine and atropine appear to be specific antagonists of histamine- and acetylcholine-induced stimulation of parietal cells. Interactions were demonstrated between cimetidine and gastrin, atropine and gastrin, respectively. In addition to a histaminergic pathway of gastrin stimulation, a cholinergic part, probably postganglionic, can be taken into consideration.Acknowledgments. I am indebted to Miss G.B. Bishop for her help with the English translation.     

Dopamine-induced relaxation in human pulmonary arteries

Dose-dependent relaxations were induced by dopamine in human pulmonary arteries that had been contracted with prostaglandin F2 alpha without alpha-adrenergic blocking agents. The dopamine-induced relaxation was inhibited by haloperidol and fluphenazine, but not by domperidone, suggesting that this relaxation was mediated via DA1 receptors.     

Endothelium-dependent relaxation induced by sodium fluoride in the rabbit ear artery

Sodium fluoride (NaF) produced concentration-dependent relaxation of isolated rabbit ear artery precontracted with norepinephrine. In contrast, an arterial preparation with the endothelium rubbed off did not relax, but contracted in response to NaF. NaF-induced relaxation was not influenced by indomethacin but was inhibited by methylene blue or NG-monomethyl-L-arginine. The results indicate that NaF relaxes the artery by releasing a so-called EDRF.     

Endothelium-dependent relaxation induced by sodium fluoride in the rabbit ear artery

Summary Sodium fluoride (NaF) produced concentration-dependent relaxation of isolated rabbit ear artery precontracted with norepinephrine. In contrast, an arterial preparation with the endothelium rubbed off did not relax, but contracted in response to NaF. NaF-induced relaxation was not influenced by indomethacin but was inhibited by methylene blue or N^G-monomethyl-L-arginine. The results indicate that NaF relaxes the artery by releasing a so-called EDRF.     

Mediation by nitric oxide of neurally-induced human cerebral artery relaxation

Human cerebral artery strips relaxed in response to non-adrenergic, non-cholinergic vasodilator nerve stimulation by electrical pulses or nicotine. The relaxation response was abolished by treatment with N^G-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibitory effect was reversed by L-, but not D-, arginine. Nitric oxide-induced relaxation was unaffected. These findings support the hypothesis that nitric oxide plays a crucial role, possibly as neurotransmitter, in transmitting information from vasodilator nerve to smooth muscle in human cerebral arteries.     

Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats

It has been proposed that the central serotonergic inputs which modulate pituitary-adrenal secretion are mediated by cholinergic neurons. We have tested this hypothesis in intact rats. Male Sprague-Dawley rats were injected with cholinergic and serotonergic agents which enhanced transmitter function and with receptor blocking agents. Agents were injected, singly and in combination, into both unstressed and stressed animals. Since the response to cholinergic agents might be due to changes to vasopressin release, Brattleboro (vasopressin deficient) rats were also injected with cholinergic agents. The level of plasma corticosterone at 1-h post-injection was determined. Results indicate that the serotonin receptor blockade decreased the stimulatory, cholinergic effect of physostigmine. Cholinergic receptor blockers did not significantly reduce the corticosterone rise induced by 5-hydroxytryptophan. These results do not support the hypothesis of cholinergic mediation of serotonergic input. Nicotinic and muscarinic receptors appeared to exert opposing influences on the system. The nicotinic receptor antagonist was able to block the stimulatory effect of physostigmine. The muscarinic receptor antagonist significantly elevated plasma corticosterone levels. No differences were found in the effect of physostigmine on Brattleboro rats as compared to controls. These data are interpreted as suggesting that 1) the acetylcholine-induced stimulation of pituitary-adrenal function is mediated, in part, by serotonergic neurons; and 2) stimulation of nicotinic receptors is facilitatory whereas stimulation of muscarinic receptors is inhibitory to pituitary-adrenal function.     

Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure

Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca²⁺ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca²⁺ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca²⁺ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca²⁺ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 μM) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca²⁺ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca²⁺ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation cycle was significantly longer in HF cells (314 ± 67 ms, n = 21, vs. 221 ± 38 ms, n = 46, mean ± SD), indicating impaired excitation-contraction uncou pling in HF cardiomyocytes. The results show that, in cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca²⁺ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result from prolongation of the action potential. Received 22 January 1998; received after revision 16 March 1998; accepted 27 March 1998     

Relaxation of isolated rabbit veins mediated by latent histamine H2-receptors

Summary Isolated rabbit veins preconstricted by either norepinephrine, methoxamine or potassium were relaxed by histamine in the presence of mepyramine, a histamine H₁-antagonist. The relaxation was not antagonized by atropine, propranolol and indomethacin but by an H₂-antagonist cimetidine. It is likely that histamine relaxes the rabbit veins through H₂-receptors.     

Isometric relaxation in rat myocardium: load dependence and influence of caffeine

When caffeine plus calcium is added to the perfusing medium, isometric relaxation of rat myocardium is no longer affected by length changes occurring during the twitch. The dependence of isometric relaxation on the initial muscle length is still present and more pronounced after caffeine addition.     

Isometric relaxation in rat myocardium: Load dependence and influence of caffeine

Summary When caffeine plus calcium is added to the perfusing medium, isometric relaxation of rat myocardium is no longer affected by length changes occurring during the twitch. The dependence of isometric relaxation on the initial muscle length is still present and more pronounced after caffeine addition.     

Inorganic phosphate promotes relaxation of chemically skinned smooth muscle of guinea-pigTaenia coli

Summary In the presence of calmodulin and phosphate and an ATP-regenerating system, Triton-treated skinned fibers of theTaenia coli could be made to contract and relax by step changes of Ca⁺⁺ within about 30 sec. In the absence of phosphate, relaxation was slower, and during this slow relaxation tension was not maintained actively. The passive tension could be abolished by phosphate (3–6 mM). Phosphate had little effect on contractile tension but decreased the speed of contraction.Supported by the Deutsche Forschungsgemeinschaft. The excellent technical assistance of Miss Claudia Zeugner is acknowledged.     

Triphasic vascular effects of thiol compounds and their oxidized forms on dog coronary arteries

The vascular effects of 2-mercaptoethanol, cysteamine, L-cysteine, glutathione (GSH), cystamine and oxidized GSH (GSSG) on the isometric tension of isolated dog coronary arterial strips were examined, and these effects were compared with the triphasic response induced by dithiothreitol (DTT); a rapid and weak contraction (phase A), an intervening slow relaxation (phase B) and a slowly-developing strong contraction (phase C) which we previously reported. The responses of the arteries induced by 2-mercaptoethanol, cysteamine and L-cysteine consisted of phases A, B and C. The order of contractile potency (ED₅₀ of phase C) was DTTL-cysteine>2-mercaptoethanolcysteamine, while the order of relaxant potency (ED₅₀ of phase B) was DTT>cysteamine2-mercaptoethanol. GSSG and cystamine mainly produced relaxation, which corresponded to phase B. The phase C contraction was specific to the reduced forms of thiols, except for GSH, which produced only relaxation. The participation of endothelial cells was not essential for the contracting or relaxing effects of the thiol compounds. The phase C contraction was depressed by W-7, a calmodulin antagonist, while phase A was not. Therefore calmodulin-dependent protein kinases may participate in phase C, not in phase A.     

Variations in the hydrothermic contraction of the rat skin as a function of the age of the animals]

The tension developed in Rat skin by hydrothermal shrinkage is modified with ageing of the animals: the temperature of maximum tension decreases from birth to 1 month, then very slowly increases with age. At higher temperatures than that of maximum tension a relaxation occurs very rapidly in young Rats and in not yet senescent adult skins. These modifications appeared to be related to those of the nature of the intermolecular collagen cross-links with ageing.     

Effect of potassium on isolated bovine facial and human saphenous veins

Summary A moderate elevation of external (K ₀ ⁺ ) (5–10 mM) induces relaxation in bovine facial and human saphenous veins. A further increase of (K ₀ ⁺ ) leads to biphasic reactions (relaxation followed by contraction). Concentrations of (K ₀ ⁺ ) higher than about 15 mM cause contractions only. The potassium-induced relaxation may be explained by the stimulation of an electrogenic sodium pump.     

Relaxation by glucagon of potassium contracture in cat ventricle

Summary Glucagon reduces K⁺-contracture, increases peak active force, but does not alter time to peak force and relaxation of the isometric twitch of cat ventricle.This study was supported by a grant-in-aid from the Florida Heart Association-Suncoast Chapter, National Institute of Health Research grant HL 19044 and NSRA Awards HL 05849 and HL 07188.The authors wish to thank Mr William Fitterman for his valuable technical and illustrative assistance.     

Influences of temperature change on the relaxation and amplitude inhibition by noradrenaline in the rabbit jejunum.

In the rabbit jejunum, the elevation of temperature within the range of 25-37 degrees C diminished the sensitivity to noradrenaline (NA) for both the relaxation and amplitude inhibition. The relaxation by NA was mainly mediated via adrenergic beta-receptors at 25, 30 or 37 degrees C. The amplitude inhibition was mediated via alpha-receptors at 37 degrees C, and both alpha- and beta-receptors at 30 or 25 degrees C.     

13C NMR-study of flexibilide,an anti-inflammatory agent from a soft cora

Summary The use of¹³C spin-lattice relaxation measurements as a probe of structure in solution is illustrated for flexibilide. Analysis of quaternary carbon relaxation behaviour indicates that the structure in solution differs from the crystal structure. The effects of lanthanide shift and relaxation reagents on¹³C spectral parameters are also reported.Acknowledgment. We thank R.J. Wells, RRIMP, for helpful discussions.