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. Cyp1a1-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.