Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension.

Cardiac fibrosis is one of the deleterious events accompanying hypertension that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemodynamic versus humoral factors, we studied the expression of genes involved in hypertrophy and fibrosis in the heart of rats treated with aldosterone for 2 months with addition of 1% NaCl and 0.3% KCl in water. This treatment induced arterial hypertension, a moderate left ventricular hypertrophy, and a decrease in plasma thyroxine. Equatorial sections of hearts from treated rats showed numerous foci of proliferating nonmuscular cells and a biventricular fibrosis. Computerized videodensitometry demonstrated an increase of collagen volume fraction by 152% and 146% and of the ratio of the perivascular collagen area and vascular area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an increase in alpha 1-I procollagen mRNA by 75% and 160% (P < .01) and in alpha 1-III mRNA by 76% and 319% (P < .01) in left and right ventricles, respectively. Atrial natriuretic peptide mRNA was induced only in the hypertrophied left ventricle. We conclude that fibrosis is occurring and involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restricted to the left ventricle, fibrosis is initiated in both ventricles, supporting the hypothesis that this cardiac response is independent of hemodynamic factors.

Efficacy of lactobionate-enriched cardioplegic solution in preserving compliance of cold-stored heart transplants.

Cardioplegic solutions of the extracellular type are commonly used as storage media for heart transplants. Because this type of formulation was not originally designed for preventing hypothermically induced edema, we assessed the effects of supplementing a standard, extracellular-like cardioplegic solution with the high molecular weight impermeant lactobionate on water content and postischemic compliance of isolated rat hearts. In one series of experiments, hearts were immersed in either a standard cardioplegic solution of the extracellular type or in the same solution supplemented with lactobionate (80 mmol/L). Hearts were then processed for measurements of water content after 4 hours, 6 hours, and 8 hours of storage at 4 degrees C. In a second series of experiments, hearts were stored in the same solutions for 4 hours and 8 hours and subsequently reperfused for 1 hour on a Langendorff column, at which time left ventricular pressure-volume curves were constructed and compared with those obtained during the preischemic perfusion. Lactobionate-treated hearts gained significantly less water than controls after 4 hours and 6 hours of storage, but the difference was no longer significant at the 8-hour time point. In contrast, the treated group yielded a significantly better recovery of compliance after both 4 hours and 8 hours of storage, suggesting that lactobionate might exert protective effects in addition to those caused by its impermeant properties, possibly involving calcium chelation and subsequent limitation of calcium-dependent contracture. Extracellular-type cardioplegic solutions are attractive because a single solution can be used during all phases of the transplantation procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of two flavonoid compounds on central nervous system. Analgesic activity.

The psychopharmacological profile of quercetin (Q) and penta-O-ethylquercetin (PQ) showed for both compounds a sedative effect on central nervous system in mice. In this set of pharmacological tests (hypothermia, spontaneous motility, psychomotor activity) penta-O-ethylquercetin always exerted a more pronounced effect than quercetin, probably due to the difference of lipophilicity. In analgesia experiments such as acetic acid-induced writhings, penta-O-ethylquercetin showed a significant dose-related effect whereas quercetin was inactive. As pretreatment with naloxone failed to antagonize the analgesic activity of penta-O-ethylquercetin, it was suggested that penta-O-ethylquercetin acted mainly peripherally.

A comparative study of the effects of sparteine, lupanine and lupin extract on the central nervous system of the mouse.

Lupin is toxic because of its alkaloid content, sparteine and lupanine in particular. Although the pharmacological properties of sparteine are well known those of lupanine have not been much studied. This paper reports procedures for extraction, purification and crystallization of lupanine, and methods for the preparation of an extract for injection of Lupinus mutabilis Sweet, and for the determination of the acute toxicity and maximum non-lethal dose (DL0) of lupanine, sparteine and lupin extract in the mouse. The three substances were tested on the central nervous system (CNS) for locomotor activity, for interaction with specific drugs used for treatment of the CNS (the stimulant drugs amphetamine and pentetrazol and the depressant drugs pentobarbital and chlorpromazine) and for analgesic activity. The results indicate that lupanine and lupin extract are less toxic than sparteine and that at the doses studied the three products have a weak sedative effect on the CNS.

Toxicological studies of deltamethrin.

Deltamethrin [( S]-alpha-cyano-3-phenoxybenzyl-cis-(1R,3R)-3-(2,2-dibromovinyl+ ++) (2,2-dimethyl-cyclopropane-carboxylate], is the most potent insecticide known at the present time. But it is also one of the most toxic pyrethroids for vertebrates. The toxicity study of deltamethrin was performed on mice and rats, and on anaesthetized dogs, the administration route being either oral or intravenous. The oral LD50 of deltamethrin suspended in 10% gum-arabic solution was 5.54 +/- 1.29 g/kg p.o. in male mice and 3.45 +/- 1.27 g/kg p.o. in female mice. In rats and anaesthetized dogs, deltamethrin at high concentrations by the oral route engendered neither mortality nor signs of intoxication. When dissolved in glycerol formal and given intravenously, the LD50 of deltamethrin was as low as 3.44 +/- 0.67 mg/kg in anaesthetized dogs. Values obtained for the toxicity of deltamethrin varied not only with the animal species and sex involved, but also with the administration routes and solvents used. Administered orally, it was 100 times less toxic when suspended in gum-arabic solution than dissolved in oil or organic solvent. Whatever the animal species, sex, administration routes and solvents employed, the poisoning symptoms of deltamethrin are identical, i.e. salivation, ataxia and choreoathetotic movements with rolling convulsions, appearing within 7 h after administration. No cellular alteration was detectable by means of optical microscopy of excised organs.

[Comparative study of the toxicity of cyanic derivatives and/or aromatic amides]. / Etude comparée de la toxicité de dérivés cyanés et/ou amides aromatiques.

The toxical potentiality of the cyanic radicle and the detoxicating characteristic of the amide group are studied following the evolution of the benzonitrile and benzamide toxicity when a cyanic or amide radicle is added to the original molecule. This comparative study shows that the presence of amide group has not always given a higher toxicity to the organic molecules that own it. It is the respective localization of the cyanic or amide radicles which appears to play the most important role.

[Spasmolytic and antinoradrenergic activities of para-hydroxybenzonitrile on the isolated duodenum and vas deferens in rats]. / Activités spasmolytique et antinoradrénergique du para-hydroxybenzonitrile sur le duodénum et le canal déférent isolés du rat.

The para-hydroxy-benzonitrile (PHB) show spasmolytic activity of the muscular of duodenum provoked by acetylcholine or barium chloride. The results obtained on the vas deferent of the rat versus the contracture effects of norepinephrine show that PHB is an antagonist of the neuromediator on the post-synaptic alpha adrenoceptors.

[Synthesis and pharmacological activity of ethyl N-acetic and N-malonic esters of heterocyclic derivatives]. / Synthèse et activité pharmacologique d'esters N-éthyl acétiques et maloniques de dérivés hétérocycliques.

The pharmacological study of heterocyclic N-ethylacetic and N-ethylmalonic esters indicate a stimulating effect on central nervous system. Some derivatives show antidepressive and psychostimulant activities.

[Pharmacologic effects of glycerolformal on the central nervous system]. / Effets pharmacologiques du glycérolformal sur le système nerveux central.

Glycerolformal is not devoid of action on mice psychomotor behaviour. Administered through the digestive tract with infralethal doses, it can exercice depressing effects on muscular strength and sensitivity to pain without affecting inquisitiveness. It opposes the stimulating effects specific to pentetrazol, amphetamine and apomorphine and is a protection against electric convulsions but tends to increase the toxicity of tryptamine.

[Pharmalogic effects of benzonitrile on the central nervous system]. / Effets pharmacologiques du benzonitrile sur le système nerveux central.

The present experiments intended to explore the psychopharmacological properties of benzonitrile on mice. Benzonitrile decreased motility, muscular force and inquisitiveness. The hypnotic effects of chloral and pentobarbital were increased by benzonitrile. The drug antagonized reserpine-induced palpebral ptosis and apomorphine-induced stereotypy. That benzonitrile was more effective against convulsions induced by pentetrazol and electric shock than those induced by strychnine suggested a central site of action. Perhaps benzonitrile interfers with the release or the action of central amines.

[Psychopharmacological study of two 3-arylsulfonyl 4-hydroxy-coumarines]. / Etude psychopharmacologique de deux 3-arylsulfonyl 4-hydroxy-coumarines.

The pharmacological study of 3-(4-chlorophenylsulfonyl) 4-hydroxy-7-methoxy- coumarine and 3-(4-methylphenylsulfonyl) 4-hydroxy-7-methoxy-coumarine shows that these derivatives present low sedative effects on the central nervous system, particularly due to their actions upon temperature and motility, more accentuated for the chloro-substituted derivative.

[Effects of alpha and beta blocker properties of parahydroxybenzonitrile on the cardiovascular system of rats]. / Etudes des effets alpha et beta bloquants du parahydroxybenzonitrile sur le système cardiovasculaire du Rat.

The study of parahydroxybenzonitrile on the cardiovascular system of the Rat shows alpha blocker properties.

[Benzonitrile and derivatives. Synthesis and pharmacological study of alkyl para-cyanophenoxy alkanoates on the central nervous system]. / Benzonitrile et dérivés. Synthèse et étude pharmacologique de para-cyanophénoxy-alcanoates d'alkyle sur le système nerveux central.

The results obtained by the pharmacological study of alkyl para-cyanophenoxy alkanoates seem to indicate that these derivatives present a sedative effect on the central nervous system. This activity increases with the number of methyl groups substituted, on ethyl para-cyanophenoxy acetate (except the motricity composent), most probably because of an increase in lipophily and therefore in the fixation on the central nervous system.