Are polyamines involved in the contractile effects of angiotensin II in the rat aorta? (Polyamines and angiotensin II in rat aorta).

Angiotensin II (AII) is a central factor involved in the pathophysiology of arterial hypertension and atherosclerosis. On the other hand, polyamines represent a family of organic cations with low molecular weight, playing intracellular regulatory roles essential for the cellular growth and differentiation. The cellular contents, the synthesis and the transport of polyamines are increased following the actions of AII, as well as of other cellular growth factors. Our results show that the administration of polyamines as pre-treatment modulates the contractile effects of extracellular AII (80 nM). This modulation is concentration-dependent and dual: the lower concentrations amplify and the higher concentrations reduce the effects of AII in the isolated rat aorta rings without endothelium. Moreover, DL-alpha-Difluoromethylomithine (DFMO), a specific inhibitor of ornithine decarboxylase, does not significantly modify the contractile effects of AII. Thus, these data suggest that polyamines generated through this metabolic pathway are not involved in the contractile effects of AII in rat aortic vascular smooth muscle.

[Polyamines antagonizing angiotensin II contractile effects in isolated rat aorta]. / Antagonizarea efectelor contractile ale angiotensinei II de catre poliamine la nivelul aortei izolate de sobolan.

Our study showed that the administration in pre-treatment of some polyamines (especially spermine and spermidine and almost null agmatine, putrescine and cadaverine) reduced the contractile effects of angiotensin II (Ang II) in isolated rat aorta. These effects might not be associated to the interference of clathrin coated vesicles (coated pits) formation or caveolae interaction (and thus to Ang II internalization through AT1 receptors). In contrast, these effects seem to be due to the interaction with voltage-gated membrane Ca2+ channels. Therefore, the alteration of transmembrane Ca2+ fluxes does not exclude the involvement of internalization process through coated pits or caveolae, since the endocytosis mediated by these phenomena essentially needs Ca2+. In addition, the inhibitory effects are dependent on the number of positive charges of the polyamine molecules.

[Interactions between angiotensin-(1-7)and angiotensin II in isolated rat portal vein]. / Interactiuni ale Angiotensinei-(1-7) cu Angiotensina II la nivelul venei porte izolate de sobolan.

Our preliminary data show for the first time the interaction between angiotensin-(1-7) (Ang-(1-7)) and angiotensin II (Ang II, 10 nM) in isolated rat portal vein. Very low concentrations (10 nM) of Ang-(1-7) have marked functional antagonizing effects on Ang II-induced contractions. High concentrations of Ang-(1-7) (1-10 mM) do not affect the effects of Ang II. The effects of low concentration Ang-(1-7) might be associated to the interaction with Ang-(1-7) specific receptors and the own contractile effects (approximatively 28%) at high concentrations might be assign to the interaction with angiotensin specific receptors AT1. But, the lack of effects of Ang-(1-7) high concentrations on Ang II-induced contractions hardly might be associated to the interaction with AT1 receptors. Although losartan was entirely blocking the Ang-(1-7) effects, there is in the literature a series of data showing that Ang-(1-7) specific receptors (or a subtype of Ang-(1-7) receptors) might be sensible (with possible high affinity) to losartan. Additional experiments are thus necessary to further clarify these interactions.

[Effects of polyamine-loaded liposomes on liver mitochondrial permeability transition]. / Efectele poliaminelor încarcate în lipozomi asupra permeabilitatii tranzitorii mitocondriale (PTM) hepatice.

The objective of the present study was represented by the effects of polyamineloaded liposomes on hepatic mitochondrial permeability transition (MPT). MPT was appreciated through the swelling of the isolated guinea-pig liver mithocondria induced by Ca2+, at 540 nm, using a diode-array 8452 UV-VIS spectrophotometer and a General Purpose software (Hewlett-Packard). Polyamines encapsulated in liposomes might inhibit the appearance of MPT induced by Ca2+, directly proportional to electrical charge: spermine > spermidine > putrescine > cadaverine. Thus, together with some previous data, it was observed that spermine may modulate hepatic MPT from the exterior, as well as from the interior of mitochondria. Moreover, spermidine and putrescine may also modulate MPT from the interior of mitochondria at low doses, and from the exterior only at high doses. The changes in mitochondrial membranes lipid composition (as done by control liposomes) are slightly influencing the MPT. The increase in membrane rigidity through the use of 40% cholesterol-enriched liposomes is drastically decreasing the appearance and development of MPT.

[Determination of several erythrocyte enzymes activity in patients with different tumors of the oral cavity]. / Activitatea unor enzime eritrocitare în cazul pacientilor cu diferite formatiuni tumorale la nivelul cavitatii orale.

Considering the influence on the molecular level of the neoplasic factors, upon several proteins, nucleic acids, one can say that some of the oncogenesis determinants are represented by genetic mutations. Free radicals, including also some organic peroxides are considered as tumour promoters, although the exact mechanism of this process in still unknown. The neoplasic disease is characterized generally by disorders of the control processes, including the one displayed on the subcellular level. Considering the enzymatic changes occurred in erythrocytes and determined by the disturbances of membrane permeability, we evaluated the response of several aggressions at the erythrocyte level, in case of maxillo-facial tumours. Our results show increase of the LDH, G-6-P-DH activity and decrease of catalase activity within the erythrocyte.

Pepstatin A is inducing contractile effects on isolated rat aorta rings.

In a series of experiments dealing with the effects of angiotensin I (AI) and angiotensinogen on isolated rat aorta we observed that pepstatin A was able to induce contractile effects by itself. The endothelin pathway was excluded by the inhibitory effects of captopril, chymostatin and amastatin. In addition, few preliminary experiments showed that the contractile effects of pepstatin A were inhibited by the pretreatment with losartan, an antagonist of AT1 angiotensin receptors. Pepstatin A-induced contractile effects on isolated rat aorta were inhibited with high potency by captopril, chymostatin and amastatin and were totally blocked by captopril + amastatin and captopril + chymostatin. Finally, we concluded that the pepstatin A-induced contractile effects on isolated rat aorta rings are dependent on an angiotensinogen vascular pool, compulsory involve an angiotensin-converting enzyme-1 (ACE-1) mediated pathway and one or more non-classical pathways for the generation of angiotensin peptides. Further experiments are necessary to elucidate the mechanisms associated to pepstatin A-induced effects.