Positive iNOS Research Articles

A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs

The endogenous peptides somatostatin and secretin are effective in the therapy of upper gastrointestinal tract bleeding and acute pancreatitis. The clinical effects may be partly brought about by changes in the regional blood flow. To evaluate the effects of somatostatin (50 and 100 μg/min over 6–8 min) and secretin (0.1 and 0.5 U · kg −1 · min −1 over 3–5 min) on tissue blood flow, particularly of the gastrointestinal tract, the tracer microsphere reference sample method was used in anesthetized dogs. Infusion of somatostatin significantly diminished gastric and pancreatic blood flow whereas no changes of duodenal and ileal blood flow could be obtained. Blood flow through spleen, kidneys and adrenal glands was increased but no changes were observed in the blood flow of other tissues. Cardiac hemodynamics remained unchanged. Secretin increased the blood flow of the duodenum, the kidneys and the adrenal glands and diminished gastric blood flow without changing pancreatic, ileal, hepatic, pulmonary and muscle blood flow. Cerebral, pituitary and myocardial blood flow was increased by a higher dose of secretin. It also evoked a slight but significant positive ino- and chronotropic effect. Since secretin and somatostatin differ in their respective effects on gastrointestinal blood flow it is suggested that the previously reported beneficial effects of both peptides on upper gastrointestinal bleeding cannot solely be attributed to changes in regional blood flow.

Characterization of the adrenoceptors mediating the positive ino- and chronotropic effect of phenylephrine on isolated atria from guinea pigs and rabbits by means of adrenolytic drugs.

Experiments were performed on isolated electrically driven and spontaneously beating atria from guinea pigs and rabbits in order to characterize the cardiostimulatory effect of phenylephrine as either β- or α-sympathomimetic.

BIOLOGICAL ACTIVITY OF DIAZONIUM COMPOUNDS (II): POSITIVE INO- AND CHRONOTROPIC ACTIONS ON GUINEA PIG ATRIA OF 4 (OR 5)-DIAZO-IMIDAZOLE-5 (OR 4)-CARBOXAMIDE

Diazonium compounds have been employed extensively to modify proteins (1-6), to study the composition and structure of enzymes and their relationships to enzyme activity (7-10), and also to produce specific antigenic determinants (11). However, these compounds have restricted interest in their use because of their lack of specificity in formation of different azo derivatives of amino acids, and because of the difficulty of obtaining them in crystalline form. Only a few investigations have been reported on pharmacological activities of diazonium compounds (12-18). During our studies on the antitumor and antibacterial activities of 4(or 5)-aminoimidazole-5(or 4)-carboxamide (a precursor of purine nucleotides) derivatives (12-14), the diazonium compound, 4(or 5)-diazoimidazole-5(or 4)-carboxamide (Diazo-ICA) was found to act as a central depressant in experimental animals (16, 17). It was reported that the diazonium group of Diazo-ICA played an important role in these biological activities (12-14, 16-17). Therefore, it was of interest to obtain detailed information on the pharmacological properties of Diazo-ICA. The present paper reports positive ino- and chronotropic effects of Diazo-ICA on isolated guinea pig atrium caused by its interaction with certain sulfhydryl groups in the tissues. It was also found that these effects of the diazonium compound on the isolated atria seemed to be partially mediated by release of catecholamine from the tissues.

THE EFFECT OF PHYSOSTIGMINE ON HEART PHOSPHORYLASE ACTIVITY IN THE SPINAL RAT

It was reported previously (1) that an increase in heart phosphorylase a following the intravenous administration of adrenaline in a dose of 10.0 μg/kg was less than that following 1.0 μg/kg, and that atropinization or vagotomy potentiated the phosphorylaseactivating action of adrenaline. In addition, a significant elevation of heart phosphorylase a was maintained for 2 hours after the injection of 1.0 μg/kg of adrenaline. From the results, it was suggested that the reflectively released endogenous acetylcholine inhibited the phosphorylase-activating action of adrenaline, and that the long-lasting elevation of heart phosphorylase a even after disappearance of the positive inotropic action of adrenaline was related to the uptake or storage mechanism of adrenaline in the heart tissue. Many investigators (2-6) demonstrated that the positive ino- and chrono-tropic responses to exogenous adrenaline of the heart were closely related to the activation of formation of cyclic 3', 5'-AMP with subsequent conversion of phosphorylase b to a. The finding (7) that injection of ganglionic stimulating agents such as DMPP and McNeil-A-343 produced an increase in heart phosphorylase a with concomitant hypertension and increase in cardiac contractile force may suggest a relationship between the level of circulating catecholamine endogenously liberated and the activity of phosphorylase in the heart. However, there are controversial reports regarding the effect of reserpine on heart phosphorylase activity: no significant change (4, 8), increase (6), and decrease (9). This is incompatible with the concept that there is a positive correlation between the amount of endogenous catecholamine and cardiac phosphorylase a activity. The inhibitory effects of injected acetylcholine and vagal stimulation on the activity of heart phosphorylase a in open-chest rats have been demonstrated by Hess et al. (7). In an attempt to study the effect of endogenous acetylcholine on heart phosphorylase a, anticholinesterase agents were injected to spinal rats. Unexpectedly, physostigmine increased the activity of the heart enzyme. Further, combined administration of adrenaline and physostigmine, both of which otherwise activated the heart enzyme, resulted in an inhibition of the enzyme activity.