Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats

0555816 - FGÚ 2023 RIV JP eng J - Článek v odborném periodiku
Řezáčová, Lenka - Vaněčková, Ivana - Hojná, Silvie - Vavřínová, Anna - Valovič, Pavol - Rauchová, Hana - Behuliak, Michal - Zicha, Josef
Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats.
Hypertension Research. Roč. 45, č. 3 (2022), s. 414-423. ISSN 0916-9636. E-ISSN 1348-4214
Grant CEP: GA ČR(CZ) GC19-08260J
Institucionální podpora: RVO:67985823
Klíčová slova: losartan * angiotensin II * intracerebroventricular * Ren-2 transgenic rats * hypertension
Obor OECD: Physiology (including cytology)
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1038/s41440-021-00775-2

Recently, we demonstrated that chronic blockade of the renin−angiotensin system (RAS) lowered the blood pressure (BP) of adult Ren-2 transgenic rats (TGR) mainly through the attenuation of central sympathoexcitation. However, the participation of central and peripheral mechanisms in the development of high BP in immature TGR remains unclear. In the present study, 6-week-old heterozygous TGR males were chronically treated with intracerebroventricular (ICV) or intraperitoneal (IP) infusions of the AT1 receptor inhibitor losartan (1 or 2 mg/kg/day) for 4 weeks. The influence of these treatments on sympathetic- and angiotensin II-dependent BP components (BP response to pentolinium or captopril, respectively) as well as on BP response to exogenous angiotensin II were determined to evaluate the participation of central and peripheral RAS in hypertension development. Chronic IP losartan administration (1 or 2 mg/kg/day) lowered the BP of immature TGR by reducing both sympathetic and angiotensin II-dependent BP components. The central action of IP-administered losartan was indicated by a reduced BP response to acute ICV angiotensin II injection. Chronic ICV administration of a lower losartan dose (1 mg/kg/day) reduced only the sympathetic BP component, whereas a higher ICV administered dose (2 mg/kg/day) was required to influence the angiotensin II-dependent BP component. Accordingly, chronic ICV losartan administration of 2 mg/kg/day (but not 1 mg/kg/day) attenuated the BP response to acute intravenous angiotensin II application. In conclusion, central sympathoexcitation seems to play an important role in hypertension development in immature TGR. Central sympathoexcitation is highly susceptible to inhibition by low doses of RAS-blocking agents, whereas higher doses also affect peripheral angiotensin II-dependent vasoconstriction.
Trvalý link: http://hdl.handle.net/11104/0330266