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CNAA / Theses / 2006 / June /

Interrelationship between the local vasotropic factors in the vascular tone regulation

Author: Mihail Todiraş
Degree:doctor habilitat of medicine
Speciality: 14.00.25 - Pharmacology, Clinical Pharmacology
Scientific consultant: Victor Ghicavîi
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific council:


The thesis was presented on the 20 June, 2006
Approved by NCAA on the 28 September, 2006


Adobe PDF document0.46 Mb / in romanian


CZU 612.731.15:615.038

Adobe PDF document 1.44 Mb / in romanian
224 pages


Endothelium, nitric oxide, nitric oxide synthesis inhibitors, renin-angiotensin system, uterine myome, uterine artery, Izoturon, Difetur


The undertaken study aimed the elucidation of the relations between NO level and basic systems controlling the vascular tone being preponderantly studied the vasotropic effects if Izoturon and Difetur in the adrenergic, cholinergic, serotoninergic, angiotensinic, kininergic and endothelinic vascular responses.

Vascular reactivity in vitro has been studied in the isolated organ bath on rat rings of aorta, and carotid and femoral arteries as well as uterine artery samples taken from patients during operation concerning uterine myoma. The central hemodynamics indices of rats with human tissular kallikrein gene hyperexpression and of mice without genes of kininogen receptors B1 and B2 have been estimated through femoral artery catheterization. The human uterine blood flow indices were determined by Doppler method.

The NO excess obtained by NO donors perfusing led to a significant reducing of the vasoconstrictor response induced by nonselective and selective α1-adrenergics, serotonin, endotheline-1 and angiotensins I and II, while the dezendothelization or NOS inhibitors use, in contrary, augmented its. NOS inhibitors markedly lowered the vascular reactivity of M-cholinomimetics, but Izoturon and Difetur effect was higher than L-NAME.

On transgenic rats with human tissular kallikrein gene hyperexpression the alternative Ang I conversion had enhanced, that was blunted by use of ACE inhibitors and nonselective metalloproteinase inhibitors. Using B1 and B2 receptor specific antagonists on these animals the role of the kininergic sites in the Ang I conversion and Ang II mediated vascular reactivity has been shown. On the other hand, the animals devoid of kininergic receptor genes were protected by toxic-septic state induced hypotension developing.

The uterine artery flow of patients with uterine myoma has increased correlatively to myoma growing, and the uterine artery reactivity has decreased in vitro on applied adrenergic, serotoninergic and angiotensinic stimuli correlatively to myoma developing rate also. In vitro, Izoturon augmented vascular response to noradrenaline, serotonin and Ang II; in vivo applied in vaginal suppositories (100 mg) it evidently reduced the uterine artery flow in dices, led to uterine hemorrhages cessation in 87,8% cases and to totally attenuation of the painful syndrome.

The perspective practice value of the obtained data would be underlined as an improvement of the therapeutic strategy regarding the modulation of the regional and systemic circulatory disorders associated by NO excess and hyperreactivity to vasoconstrictor agents.