Danukalo M. Pathogenetic features of the morpho-functional state of the dorsal vagal complex and locus coeruleus structures in experimental arterial hypertension of different genesis.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U100349

Applicant for

Specialization

  • 222 - Медицина

25-02-2021

Specialized Academic Board

ДФ 17.600.019

Zaporizhzhya State Medical University

Essay

Based on the complex study results on the pathogenetic features of the morpho-functional state of the dorsal vagal complex (the nucleus of the solitary tract and the dorsal motor nucleus) and the locus coeruleus (the blue spot) of the brainstem in etiopathogenetically distinct forms of hypertension, it has been first found that blood pressure elevation, regardless of the cause, results in morphological remodeling of these regulatory centers manifested by increased number of neurons with small nuclei, imbalance between NOS isoform and pressor and depressor neuropeptide expression. However, the direction and character of morpho- densitometric and immunohistochemical parameters were different depending on the etiopathogenesis of hypertension. A histochemical study has first allowed a detailed characteristics of changes in morpho- and densitometric parameters of the blue spot (the locus coeruleus) neuronal nuclei, the dorsal motor nucleus of the vagus and the nuclei of the solitary tract, to determine the pattern of the neuronal population distribution by the nuclear area in these structures in animals with experimental arterial hypertension of different genesis. This approach has enabled to ascertain a number of specific features characterizing the examined parameters in the studied pathology depending on the etiopathogenetic mechanisms of its occurrence and indirectly determine the functional activity of neurons in the studied structures. An intermodel comparison of the BNP and angiotensin II expression in the dorsal motor nucleus structure between the rats with endocrine-salt hypertension and essential hypertension has proved that the former had a significantly higher value of the BNP immunoreactive material specific area and a significantly higher values of the angiotensin II immunoreactive material content and specific area, but lower concentration. The morphological features of the blue spot, the nucleus of the solitary tract and the dorsal motor nucleus structures have been first comprehensively characterized using experimental animal (rat) models of hypertension (essential and endocrine-salt hypertension) corresponding to primary hypertension (essential hypertension) and secondary (endocrine-associated hypertension) in humans; the typical shared changes and etiopathogenetic distinctions between the two models have been identified. The idea of morpho-densitometric and population features of the blue spot neurons, the nucleus of the solitary tract and the dorsal motor nucleus in essential and endocrine-salt models of arterial hypertension in rats has been updated. The specificities of the nucleic acid content in the small, medium and large neuronal nuclei of the above-mentioned structures in hypertensive animals have been demonstrated. It has been found that persistently elevated blood pressure results in an increase in the number of neurons with small nuclei in the studied structures that reduces the mean nuclear area, giving rise to structural-population remodeling and changes in the number of neurons with medium- and large-sized nucleus. The modern insight into the expression profiles of nitric oxide synthase isoforms in the blue spot, the solitary tract nucleus and the dorsal motor nucleus of the brainstem structures in rats with etiopathogenetically distinct forms of arterial hypertension has been increased, and all isoforms have been first comprehensively assessed in these structures. In the rats with arterial hypertension, in contrast to the controls, both upward changes in the nitric oxide synthase isoform expression (in all the studied structures of the rats with essential arterial hypertension, and in the solitary tract nucleus and the dorsal motor nucleus structures in endocrine-salt hypertension) and downward (in the blue spot structure of the rats with endocrine- salt hypertension) have been shown. An imbalance of nitric oxide synthase isoform expression has been detected in the solitary tract nucleus and the dorsal motor nucleus structure in hypertension.

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