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

Hypertension Research volume 45, pages 414–423 (2022)Cite this article

Abstract

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.

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Acknowledgements

Technical assistance from Zdeňka Kopecká is highly appreciated. This study was supported by the Institute of Physiology, Czech Academy of Sciences (grant nr. RVO 67985823, IV) and by Joint Project of GACR and MOST, Taiwan (grant nr. 19-08260J, HR).

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Authors and Affiliations

  1. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

    Lenka Řezáčová, Ivana Vaněčková, Silvie Hojná, Anna Vavřínová, Pavol Valovič, Hana Rauchová, Michal Behuliak & Josef Zicha

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Řezáčová, L., Vaněčková, I., Hojná, S. et al. Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats. Hypertens Res 45, 414–423 (2022). https://doi.org/10.1038/s41440-021-00775-2

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