Effects of brain renin- angiotensin system inhibition in ISIAH rats with inherited stress-induced arterial hypertension

Abstract

The renin-angiotensin system (RAS) is one of the main systems regulating arterial pressure and water-salt homeostasis of the body and is involved in the pathogenesis of cardiovascular diseases. Angiotensin peptides -products of enzymatic hydrolysis of angiotensinogen -can be synthesized not only in the blood stream, but also in tissues, including various regions of the brain. Studies of local tissue RAS in the context of arterial hypertension have been conducted for a long time. It has been shown that a steady arterial pressure increase is often associated with changes in the functioning of the central (brain) RAS in various animal models of hypertensive disease and in humans. Nevertheless, it is still not completely clear whether these changes alone are sufficient for the formation of hypertensive status, and whether the components of the central RAS can be used as targets for the treatment of hypertensive disease. Effects of prolonged inhibition of the brain RAS on blood pressure and expression of RAS genes in brain and kidney tissues in ISIAH (inherited stress-induced arterial hypertension) rats were studied. Inhibition was performed using widely used pharmacological agents, losartan and benazepril. Osmotic minipumps were used to deliver drugs to the lateral ventricle of the brain. It was shown that prolonged inhibition of the central RAS, AT1 receptors in particular, can lead to a decrease in blood pressure and significant changes in the level of expression of brain RAS genes in ISIAH rats. The mRNA level of RAS genes in the kidney does not significantly change due to this inhibition. Thus, the participation of the central RAS in the pathogenesis and maintenance of hypertensive status during stress induced form of hypertensive disease in ISIAH rats was confirmed.Key words: hypertension; ISIAH rats; central RAS; mRNA expression; blood pressure.Ренин-ангиотензиновая система (РАС) -одна из основных систем, регулирующих артериальное давление и водно-солевой гомео-стаз организма и участвующих в патогенезе сердечно-сосудистых заболеваний. Ангиотензиновые пептиды -продукты фермента-тивного гидролиза ангиотензиногена -могут синтезироваться как в кровяном русле, так и в тканях, в том числе в различных отделах головного мозга. Исследования локальных тканевых РАС в контексте артериальной гипертонии ведутся уже достаточно давно. Показано, что стойкое повышение уровня артериального давления (АД) часто ассоциировано с изменениями в работе цент-ральной (мозговой) РАС в различных моделях гипертонической болезни (ГБ) и у людей. Тем не менее до сих пор до конца не ясно, являются ли данные изменения сами по себе достаточными для формирования гипертензивного статуса и можно ли использовать звенья центральной РАС в качестве мишеней для терапии гипер-тонической болезни. В работе исследовано влияние длительного ингибирования РАС головного мозга на артериальное давление и экспрессию генов РАС в тканях головного мозга и почке у крыс с наследственной стресс-индуцированной артериальной гиперто-нией (линия НИСАГ). Ингибирование проводи...

Animal Models of Hypertension (ISIAH Rats), Catatonia (GC Rats), and Audiogenic Epilepsy (PM Rats) Developed by Breeding

“…The results of several studies indicate the presence of increased basal activity in the cerebral RAAS of ISIAH rats [17,53]. This observation is confirmed by the finding that the blockade of the brain RAAS lowers BP in ISIAH rats [18]. In contrast, in the kidneys of adult ISIAH rats, the RAAS is inhibited [9,19].…”

“…Immunoblotting analysis [16] Increased basal activity of the central (brain) renin-angiotensin-aldosterone system (RAAS) in ISIAH rats. The RAAS is inhibited in the kidneys of adult ISIAH rats Real-time PCR [17][18][19] Homozygosity of ISIAH rats DNA fingerprinting [20] Genetic specificity of the ISIAH rat strain Single nucleotide polymorphisms (SNPs) [21,22] Steps toward drug discovery and translational medicine A long-term reduction in basal and stress-induced BP has been obtained via injections of dopamine precursor L-DOPA during early development (21-25 days after birth).…”