Biomedical subjects

A Costuleanu

Publications and source records attributed to A Costuleanu.

8 recordsLinked to original sources

PubMed2001

Contractile effects of angiotensin peptides in rat aorta are differentially dependent on tyrosine kinase activity.

It has been suggested that tyrosine kinase activity participates in the regulation of signal transduction associated with angiotensin II (Ang II)-induced pharmaco-mechanical coupling in rat aortic smooth muscle. We further tested the effects of genistein, a tyrosine-kinase inhibitor, and its inactive analogue, daidzein, on angiotensin I (Ang I), angiotensin III (Ang III) and angiotensin IV (Ang IV) contractions, as compared with those on Ang II. Genistein partially inhibited Ang II- and Ang I-induced contractions. The genistein-induced inhibition was more evident on Ang III and especially important on Ang IV contractile effects. Thus, Ang IV- and Ang III-induced contractions seem to be more dependent on tyrosine kinase activity than those evoked by Ang II or Ang I. Daidzein did not significantly affect the contractile effects of any of angiotensin peptides tested. These results clearly suggest that the inhibition of the action of angiotensin peptides actions by genistein is mediated by inhibition of endogenous tyrosine kinase activity. Furthermore, our data show that the type and/or intensity of tyrosine kinase activity is differentially associated with the contractile effects of different angiotensin peptides in rat aorta. Nifedipine, a blocker of membrane L-type Ca2+ channels, strongly inhibited Ang IV-induced contractions. At the same time, it significantly inhibited Ang III contractile effects as compared with Ang II and Ang I contractions. Meanwhile, we observed a close relationship between calcium influx and tyrosine kinase phosphorylation activity under the stimulatory effects of angiotensin peptides. Furthermore, genistein did not significantly influence the phasic contractions induced by angiotensin peptides in Ca2+-free Krebs-Henseleit solution. Thus, it appears that Ca2+ influx, rather than the release of Ca2+ from IP3-sensitive stores, may play a major role in the contractile effects of angiotensin peptides in rat aorta via tyrosine kinase activation. One argument against a direct action of genistein on the Ca2+ channel itself is that it did not markedly affect the K+-induced contraction (depolarisation) in rat aorta. At the same time, a potential role for tyrosine kinase activity in the process of calcium entry is suggested. An elevation of intracellular calcium via tyrosine kinase-mediated processes may mediate the actions of G-protein coupled receptor agonists in smooth muscle, including angiotensin peptides.

Angiotensin Receptor Antagonists↗

PubMed1997

Vasorelaxant properties of brefeldin A in rat aorta.

The effects of brefeldin A, a putative specific agent that disassembles the Golgi apparatus were assessed on the contractility of de-endothelised rat aorta. Brefeldin A inhibited, either as pre- or as post-treatment, the contractions elicited by K+ (75 mM) or phenylephrine (10 microM), being significantly more potent upon the latter. The thapsigargin (1 microM)-induced rat aorta contraction was less sensitive to brefeldin A inhibition. Pre-treatment with brefeldin A (30-100 microM) did not affect phenylephrine-induced transient contractions in Ca2+-free medium, but strongly inhibited the phenylephrine-induced sustained contractions upon re-admission of Ca2+ to the medium. Brefeldin A was unable to prevent Ca2+ stores refilling. We concluded that brefeldin A inhibits Ca2+ entry but not the pathways activated after Ca2+ stores depletion or the pathways responsible for replenishment of these stores in rat aorta, presumably by disassembling the Golgi apparatus network.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

TLC characterization of small unilamellar liposomes containing D-myo-inositol derivatives.

The thin-layer chromatographic (TLC) behaviour of small unilamellar liposomes containing inositol phosphates (IPs) was studied. The vesicles contained different concentrations of D-myo-inositol 1,4,5-triphosphate (IP3), D-myo-inositol 1,2,6-triphosphate (alpha-trinositol, PP 56, a novel Perstorp Pharma derivative), D-myo-inositol 1,3,4,5-tetraphosphate (IP4), D-myo-inositol 1,3,4,5,6-pentakisphosphate (IP5) and D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Migration of all liposome batches was compared to that of control liposomes (multilamellar and small unilamellar, both containing only triple-distilled water), and to that of free phosphatidylcholine (PC). The same amount of lipid was used in all situations. Thin-layer chromatography was performed with silica gel as adsorbent. The developing solvent was an n-buthanol:ethanol:water mixture in a 4:3:3 volume ratio. At doses higher than 10(-2) M liposomes containing alpha-trinositol and IP6 had a different migration than PC, MLV or SUV as well as all batches of liposomes. Physiological studies (using as model endothelized rat aorta rings) proved that in this situation they had no effects.

Animals↗

PubMedDate not supplied

TLC characterization of liposomes containing angiotensinogen, angiotensine I, angiotensine II and saralazin.

Recent studies have described intracellular binding sites for angiotensine II. In vascular smooth muscle it was found that intracellular injection of angiotensin II increases the Ca2+ level. An alternative method for intracellular delivery of drugs is represented by using liposomes. Thus, the aim of this study was to characterize liposomes filled with angiotensinogen, angiotensine I (Ang I), angiotensine II (Ang II), and saralasin by a TLC method and examine the physiological effects of these on rat vascular smooth muscle. Ang II (for all concentrations tested in the aqueous phase) and Ang I (for concentrations less than 10(-4)M) did not affect the thin-layer chromatography migration of this type of vesicle, suggesting that dose-dependent effects on physio-pharmacological experiments could be studied. On the other hand, this type of experiment could not be performed for salarasin- or angiotensinogen-filled liposomes. Administration of liposomes containing Ang II (10(-6)M), Ang I (10(-6)M), angiotensinogen (10(-6)M) and saralasine (10(-6)M) caused the contraction to isolated rat aorta smooth muscle, suggesting the presence of active intracellular binding sites.

Angiotensin I↗

PubMedDate not supplied

[The physio-pharmacological and pathological implications of the endothelins].

The papers of Furchgott and Zawadzki have widely enlarged the research field concerning the dependence of the vascular smooth muscle reactivity upon the endothelium. Besides the relaxing factors produced by the endothelium, vasoconstrictor factors have been also emphasized. The endothelial cells are also able to synthesize endothelin-like vasoconstrictor peptides. There were described some types of endothelins. They all have common structural features but substitution of certain amino-acids leads to specific effects, and all of them keep the vasoconstrictor properties. The endothelins are normal constituents of a lot of tissues (brain, endothelial and tumor cells, the spinal nodes) and of the body fluids (plasma, urine, cerebrospinal fluid etc.). The endothelins accomplish their effects by the specific receptors located in the muscle and endothelial cell membrane (ET-A and, respectively, ET-B). The endothelins action in the cell is basically based on the cytosolic Ca2+ raise. The endothelins have numerous pathological implications, especially concerning the cardiovascular pathology.

Animals↗

PubMedDate not supplied

[Dipsogenic behavior].

Hydroelectrolytic homeostasis assumes balance between the intake and elimination of water and electrolyte, according to the necessities of the organism. The water intake is made mainly by fluid ingestion. The necessity to drink is a subjective sensation which is the expression of an objective situation, because it translates the homeostatic deviations. The ingestion of water is motivated (reparatory thirst), when it appears after hydric and electrolytic imbalances (ex. a decrease of the fluid volume, increase in the plasmatic osmolarity) or is manifested without an objective reason (unreparatory thirst).

Animals↗

PubMedDate not supplied

[The effects of the intraventricular administration of captopril on water and ion metabolism in the rst].

The effects of the conversion enzyme on the hydroelectrolytic balance in adult rats, maintained in standard lab conditions have been followed. The administration protocol for the conversion inhibitor (captopril) produced a blocking of the transformation of angiotensin I in angiotensin II only at the level of the cerebral structures, during the whole period of the treatment (40 micrograms/kg x 3/24 hours). Following the intracerebroventricular (ICV) administration of captopril, the fluid ingestion decreased diuresis and urinary elimination of Na+ and Ca++ increased. The results plead for the existence of a cerebral renin-angiotensin system, which intervenes in the control of the hydroelectrolyte metabolism.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Contractile effects of intracellularly administered angiotensin II are partially dependent on membrane receptors internalization in isolated rat aorta.

In the present study we used the isolated rat aorta as a model to characterize the modulation of contractile effects of extra- and intracellularly administered angiotensin II by dithiothreitol (DTT) and hyperosmotic sucrose. DTT inactivation of AT1 receptor as well as disruption of the clathrin-coated pits by hyperosmotic sucrose significantly inhibited the contraction induced by intracellularly administered AII. We suggest that these intracellular effects of angiotensin peptides are associated with AT1 receptor activation/internalization and may thus be part of the mechanism of angiotensin peptides direct contractile effects in the vascular smooth muscle.

Angiotensin II↗