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Biomedical subjects

A G Herman

Publications and source records attributed to A G Herman.

At least 145 records · Page 8Linked to original sources
PubMed1991

15-lipoxygenase metabolites of arachidonic acid evoke contractions and relaxations in isolated canine arteries: role of thromboxane receptors, endothelial cells and cyclooxygenase.

The 15-hydroperoxy metabolite of arachidonic acid (15-hydroperoxyeicosatetraenoic acid; 15-HPETE) and its hydroxyderivative 15-hydroxyeicosatetraenoic acid (15-HETE) are known to evoke contractions in a variety of isolated blood vessels. In this study, segments of isolated canine coronary, splenic, femoral and renal arteries were exposed to 15-HETE and 15-HPETE; both metabolites induced small basal relaxations followed by contractions at higher concentrations. The contractions were augmented by indomethacin and could be blocked by the thromboxane A2 receptor antagonists BM13177 and BM13505. In vessels in which the tone was raised with prostaglandin F2 alpha, both 15-lipoxygenase metabolites evoked marked relaxations, which were in part dependent on the presence of the endothelium. When the segments were contracted with norepinephrine or increased KCl concentration, 15-HETE and 15-HPETE induced relaxations followed by additional contractions. The relaxations to the fatty acid derivatives were not inhibited by BM13505. In tissues without endothelium, the relaxations to 15-HETE and 15-HPETE were completely blocked by indomethacin; in tissues with endothelium, indomethacin only partly inhibited the relaxations to 15-HETE, whereas the drug did not interfere with the relaxing effects of 15-HPETE. Our experiments indicate that in isolated canine arteries 15-lipoxygenase metabolites of arachidonic acid can 1) induce contractions, most likely by direct activation of thromboxane A2 receptors on smooth muscle cells, and 2) evoke relaxations that are in part endothelium dependent; the endothelium-independent part of the relaxations was inhibited by indomethacin. Thus, the relaxations to these metabolites seem to occur via the release of an endothelium-derived relaxing factor and via production of a cyclooxygenase metabolite.

Animals↗
PubMed1990

Release and vascular activity of endothelium-derived relaxing factor in atherosclerotic rabbit aorta.

A diet containing 0.3% cholesterol was given to male New Zealand rabbits for 16 weeks; this produced atherosclerotic lesions (fatty streaks) on 80% of the intimal surface of the thoracic aorta and on 45% of the intimal surface of the abdominal aorta. The endothelium-dependent relaxations induced by acetylcholine, substance P and ionophore A23187 were inhibited in the atherosclerotic aortas. Besides the endothelium-independent relaxations induced by nitroglycerine, the relaxations induced by atrial natriuretic peptide (ANF) were also significantly reduced in the more atherosclerotic thoracic aorta. In bioassay experiments it was found that acetylcholine and substance P caused a smaller release of endothelium-derived relaxing factor (EDRF) from atherosclerotic thoracic aortas than from control thoracic aortas: the EDRF released by the vasodilators evoked less relaxation in atherosclerotic detector abdominal aortas than in control detector abdominal aortas. Nitric oxide evoked significantly less transient relaxation in the atherosclerotic thoracic and abdominal aortas than in the respective control tissues. The data indicate that as experimental atherosclerosis in the rabbit progresses, both vascular activity and EDRF release become affected; this leads to a complete loss of endothelium-dependent relaxation in the more atherosclerotic blood vessels.

Acetylcholine↗
PubMed1990

Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction.

The nature of the inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitter was studied in circular muscle strips of the canine terminal ileum and ileocolonic junction. Nitric oxide (NO) induced tetrodotoxin-resistant NANC relaxation, similar to that induced by electrical stimulation or acetylcholine (ACh). Incubation with the stereospecific inhibitors of NO biosynthesis, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA), resulted in an increase of basal tension in the ileocolonic junction which was partly reversed by L-arginine but not by D-arginine. Moreover, L-NMMA and L-NNA, but not D-NMMA, concentration dependently inhibited the NANC relaxation in response to electrical stimulation and ACh, but not that in response to NO or nitroglycerin. This inhibitory effect was reversed by L-arginine but not by D-arginine. Hemoglobin reduced the NANC relaxation in response to electrical stimulation, ACh and nitroglycerin, and abolished the responses to NO. Our results suggest that NO or a NO releasing substance mediates the NANC relaxation in the canine terminal ileum and ileocolonic junction.

Animals↗
PubMed1990

The effect of a developing neo-intima on serotonergic and adrenergic contractions.

In the present study we used a new model, in which the positioning of a non-occlusive collar around the rabbit carotid artery results, within 7 days, in the generation of a neo-intima, a precursor lesion of atherosclerosis. We investigated the effects of this intimal proliferation on the responsiveness to serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NOR) after 1, 2 and 7 days. Already after 1 day the collar-treated arteries were more sensitive to 5-HT, but not to NOR. This sensitivity persisted over a period of 7 days. However, the development of a neo-intima diminished the maximum contractile force to NOR after 2 and 7 days, but not to 5-HT. These results demonstrate that there is a relatively selective increase in sensitivity to 5-HT during neo-intima formation, even without hyper-cholesterolaemia.

Animals↗
PubMed1990

Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter.

Inhibitory non-adrenergic non-cholinergic (NANC) nerves are thought to be important in the autonomic innervation of the gastrointestinal tract and other organ systems. The nature of their neurotransmitter is still debated. Speculation that nitric oxide (NO), formed from L-arginine in neuronal structures and other cells, could act as a neurotransmitter, is not yet supported by demonstration of its release upon nerve stimulation. Using a superfusion bioassay, we report the release of a vasorelaxant factor upon stimulation of the NANC nerves in the canine ileocolonic junction. Several pieces of evidence, including the selectivity of the bioassay tissues, chemical instability, inactivation by superoxide anion and haemoglobin, inhibition by NG-nitro-L-arginine (L-NNA) and potentiation by L-arginine all indicated that NO accounted for the biological activity of this transferable NANC factor.

Animals↗
PubMed1990

Nutmeg oil: identification and quantitation of its most active constituents as inhibitors of platelet aggregation.

Three distilled or commercially available nutmeg oils were analysed and their chemical composition compared with their capacity to inhibit platelet aggregation in vitro. It could be clearly shown that eugenol and isoeugenol play the major role in the detected activity of nutmeg. Medicinally, it appears that nutmeg oil and nutmeg powder can be replaced by eugenol and/or isoeugenol.

Animals↗
PubMed1990

GABAA receptor-mediated stimulation of non-adrenergic non-cholinergic neurones in the dog ileocolonic junction.

1. The inhibitory effects of gamma-aminobutyric acid (GABA), the GABAA receptor agonist homotaurine and the GABAB receptor agonist (+/-)-baclofen were investigated on circular muscle strips of the dog terminal ileum and ileocolonic junction. 2. In the presence of atropine, GABA and homotaurine induced concentration-dependent relaxations, similar to the non-adrenergic non-cholinergic (NANC)-mediated relaxations evoked by electrical stimulation or by acetylcholine. The ileocolonic junction was more sensitive to GABA and homotaurine than the ileum. (+/-)-Baclofen had no effect. Cross desensitization only occurred between GABA and homotaurine. 3. The GABAA receptor antagonist bicuculline shifted the concentration-response curves to GABA and homotaurine to the right. The maximal relaxation to GABA remained unaffected. 4. GABA-induced relaxations were not inhibited by timolol, guanethidine, domperidone, hexamethonium and desensitization to ATP, but were abolished by tetrodotoxin. 5. Bicuculline, and pretreatment with GABA or (+/-)-baclofen had no effect on the NANC-evoked relaxations to electrical stimulation and acetylcholine. 6. In conclusion, GABA stimulates GABAA receptors located on inhibitory NANC neurones in the dog ileocolonic junction. Our results suggest that it is unlikely that GABA is the final inhibitory NANC neurotransmitter.

Acetylcholine↗
PubMed1990

Cholinergic and adrenergic contractile properties of the canine ileocolonic junction.

A comparative study of cholinergic and adrenergic mechanisms was performed on isolated circular muscle strips of the canine ileum, ileocolonic junction and colon. Cholinergic agonists evoked atropine sensitive contractions, which were most prominent in the colon. The presence of neostigmine to inhibit acetylcholinesterase did not alter the relative sensitivities of the tissues to acetylcholine. The different maximal contraction to cholinergic agents discriminates the colon from the ileum and the ileocolonic junction. Alpha adrenoceptor agonists produced greater contractions in the ileocolonic junction and only marginal contractions in the colon. Phentolamine completely and prazosin and yohimbine partially blocked the response of the ileocolonic junction to norepinephrine, suggesting the involvement of both alpha-1 and alpha-2 adrenoceptors. As in other sphincteric gut smooth muscle, the contractile effects of alpha adrenergic agents are more important than the inhibitory ones. The different effects of cholinergic and adrenergic agents on the ileocolonic junction, as compared sphincteric properties in the canine ileocolonic junction. sphincteric properties in the canine ileocolonic junction.

Acetylcholine↗
PubMed1990

Evidence against ATP being the inhibitory transmitter released by nonadrenergic noncholinergic nerves in the canine ileocolonic junction.

The nonadrenergic noncholinergic (NANC) relaxations in response to electrical stimulation and acetylcholine in the canine terminal ileum and ileocolonic junction were further characterized and the possible involvement of the putative NANC neurotransmitter ATP was investigated. During a norepinephrine-induced contraction, noncumulative administration of ATP and the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP) induced concentration-dependent relaxations in both the terminal ileum and ileocolonic junction; these responses were not inhibited by atropine, timolol or guanethidine. Desensitization to ATP blocked the ATP-induced relaxations, but not those to electrical stimulation or acetylcholine. All relaxations were abolished by tetrodotoxin. Theophylline or dipyridamole had no effect. Hexamethonium and desensitization to DMPP blocked the relaxations to acetylcholine and DMPP, but not those to electrical stimulation or ATP. The relaxations to acetylcholine, ATP and DMPP were inhibited by lidocaine. Thus, in the canine terminal ileum and ileocolonic junction, ATP induces NANC relaxations of neuronal origin, but ATP is unlikely to be the final NANC neurotransmitter mediating the relaxations to electrical stimulation or acetylcholine. These data also extend our previous observations on the presence of an inhibitory nicotinic innervation in these tissues.

Acetylcholine↗
PubMed1990

Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction.

The effects of 5-hydroxytryptamine (5-HT), the 5-HT1-like receptor agonist 5-carboxamidotryptamine and the 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine were studied on circular muscle strips of the canine terminal ileum and ileocolonic junction. Serial administration of 5-HT or of 5-carboxamidotryptamine induced slow tonic contractions that at higher concentrations of 5-HT (10(-4)-3 x 10(-4] were preceded by an initial relaxation and a fast phasic contraction. The concentration-response curves to both agonists were competitively shifted to the right by the mixed 5-HT1/5-HT2 receptor antagonist methysergide. The initial relaxation and fast phasic contraction were inhibited by the 5-HT3 receptor antagonist ICS 205-930 and tetrodotoxin. Atropine blocked the fast phasic contraction, but enhanced the relaxation. During acetylcholine-induced contractions, 5-HT and 2-methyl-5-hydroxytryptamine (greater than or equal to 10(-5) M), but not 5-carboxamidotryptamine, evoked relaxations that were blocked by ICS 205-930 and tetrodotoxin, but not by adrenoceptor antagonists. Thus, in the canine terminal ileum and ileocolonic junction, 5-HT stimulates neuronal 5-HT3 receptors and excitatory 5-HT1-like receptors located on smooth muscle. Stimulation of the 5-HT3 receptors results in an acetylcholine-mediated contraction and a relaxation mediated by an as yet unknown nonadrenergic noncholinergic neurotransmitter.

Animals↗
PubMed1989

Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction.

The effects of cholinergic agents, electrical stimulation and vasoactive intestinal polypeptide (VIP) were studied on transverse muscle strips of the canine ileum, ileocolonic junction and colon. Acetylcholine, methacholine and carbachol caused concentration-dependent contractions in the three gut tissues. Only acetylcholine (greater than 10(-5) M) evoked transient relaxations in the ileum and the ileocolonic junction before the onset of contractions. During contractions by noradrenaline, acetylcholine induced relaxations, which were enhanced by atropine; electrical stimulation also caused frequency-dependent relaxations. Propranolol or naloxone did not affect the relaxations. Hexamethonium, cocaine or lidocaine inhibited the relaxations induced by acetylcholine but not those evoked by electrical stimuli. Tetrodotoxin inhibited all relaxations, VIP did not evoke relaxation in the ileocolonic junction. These data indicate that acetylcholine stimulates nicotinic receptors on non-adrenergic non-cholinergic neurons, which do not release VIP or opioids. It is thus suggested that there is a nicotinic inhibitory innervation at the canine ileum and ileocolonic junction.

Acetylcholine↗
PubMed1989

Evidence for the involvement of prostaglandins in modulation of acetylcholine release from canine bronchial tissue.

A sensitive high pressure liquid chromatography (HPLC) method was used to measure acetylcholine release from canine bronchial tissue in response to electrical stimulation. Indomethacin enhanced the efflux of acetylcholine, an effect that was reversed by the addition of prostaglandin E2 (PGE2). Prostaglandin D2 (PGD2) had no effect on acetylcholine output. These data suggest that prostaglandins, possibly PGE2, are involved in a negative feedback control mechanism for acetylcholine release in canine bronchi.

Acetylcholine↗
PubMed1989

Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo.

We have investigated the ability of recombinant TNF (mouse and human) to produce acute inflammatory lesions in an established experimental model of inflammation. Upon intradermal injection in rabbit skin, TNF, in amounts as low as 3 x 10(-14) mol/site, was found to be very potent at inducing local neutrophil accumulation and neutrophil-dependent oedema formation, thereby fulfilling two important criteria to be considered as an inflammatory mediator. Our findings further indicate that the pro-inflammatory properties of TNF are probably more related to its immediate stimulatory effects on neutrophils rather than to its slow (protein biosynthesis-dependent effects on endothelial cells. Our data thus show that very low amounts of mouse and human recombinant TNF can initiate an acute inflammatory reaction in vivo in rabbit skin and that TNF is able to evoke two of the four cardinal signs of inflammation.

Animals↗
PubMed1989

Different pro-inflammatory profiles of interleukin 1 (IL 1) and tumor necrosis factor (TNF) in an in vivo model of inflammation.

The pro-inflammatory properties of IL 1 and TNF were investigated in an in vivo model of inflammation. IL 1 induced PMN leukocyte accumulation that was slow in onset, reaching a peak rate at 3-4 h and that was inhibitable by Actinomycin D and Cycloheximide. PMN leukocyte emigration was not associated with any significant plasma leakage. In contrast, TNF induced PMN leukocyte accumulation and oedema formation, that were rapid in onset and very short of duration (t1/2 6-10 min). TNF-induced plasma leakage was PMN leukocyte-, but not protein biosynthesis-dependent. The differences in time course and biological profile suggest that IL 1 and TNF exert their pro-inflammatory effects in vivo via different mechanisms.

Disease Models, Animal↗
PubMed1989

Evaluation of the functional integrity of endothelium in perfused lungs.

Prostacyclin (PGI2) formation and the saturable uptake of 5-hydroxytryptamine (5HT) were studied as indices of endothelial integrity in isolated lungs. 5HT uptake was characterized by its kinetic parameters Km and Vmax. These were calculated from multiple indicator dilution data on the basis of an organ model of 5HT uptake. Perfused dog lung lobes were exposed to plasma activated with yeast (YAP) or zymosan (ZAP). YAP induced a transient elevation of Km. This increase probably reflects endothelial injury. Vmax remained unchanged, suggesting that the perfused endothelial surface remained stable. PGI2 biosynthesis was negligible in the control period, but started immediately after exposure to ZAP or YAP. It was proportional to the transient elevation of Km and to the pulmonary oedema. The data suggest that PGI2 might be a marker of severe endothelial distress.

Animals↗
PubMed1989

Pharmacological features of the vasodilation induced by tertatolol in isolated perfused rat kidneys.

The aim of the studies summarized in the present review was to obtain a pharmacological characterization of the in vitro renal vasodilator action of tertatolol. In isolated Tyrode-perfused rat kidneys, previously constricted with norepinephrine, serotonin or BaCl2, tertatolol evokes vasodilatation. These dilator responses cannot be explained by an interaction of tertatolol with alpha- or beta-adrenoceptors, muscarinic or nicotinic receptors, opioid receptors, dopamine receptors or histamine receptors, and they occur independently of the release of prostaglandins. Since methylene blue, an inhibitor of the soluble form of guanylate cyclase, reduces the renal dilator effect of tertatolol, this action could ultimately depend, at least in part, on the production of cyclic guanosine monophosphate; in this respect, the renal effects of tertatolol and atrial natriuretic factor (ANF) are different. From experiments performed with canine renal arteries and with the perfused rat mesentery, it can be concluded that the effect of tertatolol is more pronounced at the level of the resistance vessels. The in vitro renal dilator response observed with tertatolol may help to explain the beneficial effect on the renal circulation observed in both humans and experimental animals treated with the compound.

Adrenergic beta-Antagonists↗
PubMed1989

Prognostic value of prostaglandin F2 alpha concentrations in breast carcinoma.

Prostaglandin F2 alpha (PGF2 alpha) concentrations were measured by radioimmunoassay in homogenised primary tumours from 57 patients with breast cancer. These patients were followed up from 60 to 78 months (median 63 months) after surgery and PGF2 alpha concentrations were related prospectively to metastatic spread and survival. The amounts of PGF2 alpha varied greatly in the different tumours (range 0-90 ng/mg protein), but no significant association was found between PGF2 alpha concentrations and disease free survival, time of relapse, site of recurrence, or overall survival. It therefore seems unlikely that measurement of PGF2 alpha in breast carcinoma is important in the prognosis of the disease.

Adult↗