TY - JOUR

T1 - Hypothalamic norepinephrine concentration and heart mass in hypertensive isiah rats are associated with a genetic locus on chromosome 18

AU - Redina, Olga E.

AU - Smolenskaya, Svetlana E.

AU - Polityko, Yulia K.

AU - Ershov, Nikita I.

AU - Gilinsky, Michael A.

AU - Markel, Arcady L.

N1 - Funding Information: Funding: Genotyping was supported by budget project No. 0259-2021-0015. SNPs analysis was supported by budget project No. 0259-2021-0013. The mathematical processing of the obtained data and the preparation of the results for publication was supported by the Russian Foundation for Basic Research, grant No. 20-04-00119a. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - The relationship between activation of the sympathetic nervous system and cardiac hy-pertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1). Nucleotide substitutions that may be involved in the formation or absence of association with blood pressure in different rat strains are discussed.

AB - The relationship between activation of the sympathetic nervous system and cardiac hy-pertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1). Nucleotide substitutions that may be involved in the formation or absence of association with blood pressure in different rat strains are discussed.

KW - Heart mass

KW - ISIAH hypertensive rat strain

KW - Norepinephrine concentration in the hypothalamus

KW - QTL analysis

KW - SNPs

UR - http://www.scopus.com/inward/record.url?scp=85100505788&partnerID=8YFLogxK

U2 - 10.3390/jpm11020067

DO - 10.3390/jpm11020067

M3 - Article

C2 - 33498741

AN - SCOPUS:85100505788

VL - 11

SP - 1

EP - 15

JO - Journal of Personalized Medicine

JF - Journal of Personalized Medicine

SN - 2075-4426

IS - 2

M1 - 67

ER -