Mediation of arachidonic acid metabolite(s) produced by endothelial cytochrome P-450 3A4 in monkey arterial relaxation.

We investigated mechanisms of endothelium-dependent relaxation by acetylcholine resistant to indomethacin and N(G)-nitro-L-arginine and sensitive to cytochrome P-450 (CYP) inhibitors or charybdotoxin + apamin in the monkey lingual artery. Treatment with quinacrine, an inhibitor of phospholipase A2, abolished the relaxation by acetylcholine. However, treatment with alpha-glycyrrhetinic acid, an inhibitor of gap junctions, or catalase, an enzyme which dismutates hydrogen peroxide to form water and oxygen, did not affect the relaxation by acetylcholine. Immunohistochemistry demonstrated the presence of CYP3A4 in endothelial cells of the artery. Anti-CYP3A4 antibody inhibited relaxations by products of arachidonic acid incubated with human liver microsomes rich in CYPs in the endothelium-denuded artery. Purified CYP3A4 produced epoxyeicosatrienoic acids (EETs) from arachidonic acid, and the production was abolished by a selective CYP3A inhibitor, ketoconazole. It may be concluded that endothelium-derived relaxing substance(s) other than nitric oxide and prostanoids in the monkey lingual artery opens charybdotoxin + apamin-sensitive K+ channels in smooth muscle cells, and arachidonic acid metabolite(s) produced by endothelial CYP3A4 is likely to be the major substance.     

Untersuchungen über den Ablauf der Muskelermüdung bei wechselnder Belastung und unter dem Einfluß von Giften und Ionen

Zusammenfassung Es wird die Bedeutung der Methode der Ermüdungskurven mit wechselnder Belastung für das Alles-oder-nichts-Gesetz erörtert und die Methode weiterhin angewandt zur Analyse der Wirkung einiger Pharmaka und Ionen auf den Muskel. Zugleich wird an Hand der Kurven ein Ausdruck für die Dehnbarkeit der Muskeln im kontrahierten und nicht kontrahierten Zustand gewonnen.In Versuchen mit Alkohol verschiedener Konzentration, mit Coffein, Acetylcholin, Natriumrhodanid, Säure, Alkali, Calcium- bzw. Kaliumüberschuß sowie mit calcium- und kaliumfreien Lösungen wurden charakteristische Veränderungen der Ermüdungskurven bei verschiedener Belastung sowie der Dehnbarkeit festgestellt.     

Regional difference in the response mediated by beta 1-adrenoceptor subtype in bovine cerebral arteries.

Helical strips of bovine rostral cerebral arteries (anterior cerebral, middle cerebral, and internal carotid artery) responded to norepinephrine with contractions, whereas the caudal cerebral arteries (posterior communicating, posterior cerebral, and basilar artery) relaxed in response to the amine. After blockade of alpha-adrenoceptors, norepinephrine-induced rostral artery contractions were reversed to relaxations, which were smaller than those in the caudal arteries. Isoproterenol, dobutamine, and terbutaline produced greater relaxations in caudal than in rostral arteries, but forskolin relaxed these arteries to a similar magnitude. The isoproterenol-induced relaxation was not affected by removal of the endothelium. Maximal relaxations induced by terbutaline in caudal arteries were much inferior to those by isoproterenol, norepinephrine, and dobutamine. Relaxations caused by isoproterenol, norepinephrine, and terbutaline in the caudal arteries were attenuated by metoprolol, but not influenced by butoxamine. Relaxations mediated possibly by beta 1-adrenoceptor subtypes are greater in bovine caudal cerebral arteries than in the rostral arteries. The heterogeneity does not appear to be associated with the different ability of cyclic AMP to relax arterial smooth muscle but with the difference of beta-adrenoceptor populations and/or processes from the receptors to adenylate cyclase.     

Microvascular architecture of the palatine mucosa in the common squirrel monkey (Saimiri sciureus).

Detailed observations were made of the structure and microvasculature of the palatine mucous membrane of the common squirrel monkey (Saimiri sciureus) by means of the plastic injection method under a scanning electron microscope. The findings obtained were compared with those of the Japanese monkey and other mammals. The osseous palate was flat horizontally and a pair of incisive foramina were apparently open at the anterior end of the hard palate. At the posterior end of the osseous palate, the pterygopalatine incisurae were found bilaterally. The incisive papilla was not obvious in form and size, and a pair of openings of the incisive canal were always situated on both sides of the papilla. The transverse palatine plicae or ridges numbered 7 or 8 symmetrically. They arched posterolaterally with an anterior protrusion near each median end. Posterior plicae were underdeveloped. Numerous openings of the palatine glands were found in the soft palatine mucosa. The arteries supplying the palate were the major palatine artery passing through the major palatine foramen and the soft palatine artery passing through the pterygopalatine incisura. The major palatine artery extended forwards giving off numerous medial and lateral branches, and its end on the respective side entered a small foramen located lateral to the incisive foramen. Medial and lateral branches formed the submucous arterial network. Arterioles diverging from this network were directed to the epithelial surface and formed an arterial network in the lamina propria. Further, capillaries diverging from the latter network built up the subepithelial capillary network immediately beneath the epithelium. Capillary loops sprouting from the capillary network were found in the form of a simple hair-pin without locational differences in their heights. The microvascular architecture thus displayed some similarity with that of the Japanese monkey. However, the vascular networks in the lamina propria and submucous layer were not distinct in size and scale as compared to those of the Japanese monkey. These differences may be related to the stature, living environment and food habits of this species.     

Thymic metastasis from prostatic carcinoma: Report of a case

The thymus is an important organ involved in cell-mediated immunological function, and to our knowledge, there has never been a case of thymic metastasis reported. We recently examined a 65-year-old man who presented at our department with a cough and shortness of breath on exertion. He had a history of prostatic carcinoma for which he had undergone an orchiectomy 11 years previously. Investigations disclosed a mediastinal tumor, 14×9 cm in size, and histological examination of the resected tumor confirmed a diagnosis of thymic metastasis from prostatic carcinoma.     

Thiopental attenuates relaxation and cyclic GMP production in vascular smooth muscle of endotoxin-treated rat aorta, independent of nitric oxide production

As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by nitric oxide donor drugs, we have tested if it suppresses cGMP formation and increases vascular tone after induction of calcium- calmodulin-independent nitric oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental on tension, cGMP concentrations and nitrite accumulation were determined. Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted aortic rings before LPS treatment, but caused no significant effects on tension in the presence of L-arginine 10 microgramsmol litre-1 after LPS treatment. L-Arginine 1 microgramsmol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated aorta in a concentration- dependent manner. This was reduced by thiopental 0.3-1 mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations of nitrite, the end product of nitric oxide; this was not affected by thiopental 1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS-induced vascular smooth muscle without affecting nitric oxide production.