The Absence of Sympathoexcitation During the Development of Hypertension in Cyp1a1 Ren-2 Transgenic Rats

0504693 - FGÚ 2020 RIV CZ eng J - Journal Article
Zicha, Josef - Hojná, Silvie - Kopkan, L. - Červenka, L. - Vaněčková, Ivana
The Absence of Sympathoexcitation During the Development of Hypertension in Cyp1a1 Ren-2 Transgenic Rats.
Physiological Research. Roč. 68, č. 2 (2019), s. 329-334. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA MZd(CZ) NV15-25396A
Institutional support: RVO:67985823
Keywords : indole-3 carbinol * blood pressure * angiotensin II * sympathetic nervous system * nitric oxide * Rho kinase pathway * fasudil
OECD category: Cardiac and Cardiovascular systems
Impact factor: 1.655, year: 2019
Method of publishing: Open access
http://www.biomed.cas.cz/physiolres/pdf/2019/68_329.pdf

The insertion of mouse renin gene (Ren-2) into the genome of normotensive rats causes a spontaneous rise of blood pressure (BP), leading to an angiotensin II (Ang II)-dependent form of hypertension in transgenic (mRen-2)27 rats (TGR). However, enhanced sympathetic BP component was demonstrated in heterozygous TGR aged 20 weeks. In the present study we used another model, i.e. Cyplal-Ren-2 transgenic rats (iTGR) in which hypertension can be induced by natural xenobiotic indole-3 carbinol (I3C) added to the diet. We investigated whether the development of high blood pressure (BP) in 5-month-old iTGR animals fed I3C diet for 10 days is solely due to enhanced Ang II-dependent vasoconstriction or whether enhanced sympathetic vasoconstriction also participates in BP maintenance in this form of hypertension. Using acute sequential blockade of renin-angiotensin system (RAS), sympathetic nervous system (SNS) and NO synthase (NOS) we have demonstrated that the observed gradual increase of BP in iTGR fed I3C diet was entirely due to the augmentation of Ang II-dependent BP component without significant changes of sympathetic BP component. Thus, the hypertension in iTGR resembles to that of homozygous TGR in which high BP was entirely dependent on Ang II-dependent vasoconstriction. Moreover, our measurements of acute BP response to Rho kinase inhibitor fasudil in animals subjected to a combined blockade of RAS, SNS and NOS indicated the attenuation of basal calcium sensitization in both iTGR and homozygous TGR.
Permanent Link: http://hdl.handle.net/11104/0296273