Functional Significance of Angiotensin Receptor Type 2 in the Neuroplasticity of Autonomic Ganglia in (mRen2)27 Transgenic Hypertensive Rats

The over-expression of Ren-2(d) gene in (mRen2)27 rats leads to development of hypertension mediated by the renin-angiotensin-system axis and exaggerated sympathetic nerve activity. Exogenously applied angiotensin II (AngII) on the superior cervical ganglion evokes ganglionic compound action potentials (gCAP) and ganglionic long-term potentiation (gLTP). We studied the functional role of angiotensin receptors and expression of reactive oxygen species marker, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) proteins in AngII–induced postganglionic transmission. Bath-applied AngII revealed that the indices of ganglionic transmission, synaptic strength of gCAP, and decay time for gLTP are remarkably prolonged in (mRen2)27 rats and were abolished by an angiotensin receptor blocker (ARB), suggesting postganglionic AngII Type 1 (AT(1)) receptor localization and mediation. Receptor density for AT(1) was similar in (mRen2)27 and control animals, and quantitative reverse transcription polymerase chain reaction revealed that it is consistent with the mRNA profile. Furthermore, immunocytochemistry analysis showed similar AT(1) receptor distribution and signals. However, assessment of Type 2 (AT(2)), Ang-(1-7)-MAS and NOX4-specific proteins showed that AT(2) receptor protein expression was 4-fold lower, consistent with a low mRNA profile. MAS receptor expression was 10-fold lower and NOX4 protein was 2-fold lower. Despite similarity in the densities of AT(1) receptor, the low levels of the components of the protective arm of the renin-angiotensin system at the ganglia may contribute to the differential superior cervical ganglion sensitivity to AngII. The lower NOX4 affects reactive oxygen species balance and possibly results in activation of downstream pathways to promote increased sympathetic nerve activity. We speculate that the significant diminution in AT(2,) MAS, and NOX4 protein expressions may play an indirect role in the alteration and efficacy of gCAP and gLTP in hypertension.