Abstract 1628: Elevated Angiotensin II in Rat Nodose Ganglia Mediates Diabetes-Blunted Arterial Baroreflex Sensitivity
Clinical trials and studies using animal models have confirmed the contribution of arterial baroreflex impairment in causing excess morbidity and mortality in type-1 diabetes (DM1). Using a DM1 rodent model, our lab has previously shown that elevation of endogenous angiotensin II (Ang II) level in nodose ganglia (NG) is associated with enhanced currents of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and reduced cell excitability in neurons. In this study, we examined whether elevated Ang II in NG contributes to the blunted baroreflex sensitivity in a streptozotocin-induced DM1 rodent model. Using RT-PCR, western blot and immunofluorescent staining, we found that mRNA and protein expression of angiotensin 1 (AT1) receptors in NG were elevated in DM1 rats compared to those in the sham rats. Using Ang II 125 I radioimmunoassay, Ang II concentration in NG was significantly higher in DM1 rats than that in sham rats (101. 6 ± 4.8 vs. 38.9 ± 4.2 pg/mg protein, p < 0.05). The reflex decreases in blood pressure and heart rate evoked by unilateral steady-frequency aortic depressor nerve (ADN) stimulation were blunted in DM1 rats. Topical microinjection of L158,809 (AT1 receptor antagonist, 20 μM, 50 nl) and cesium chloride (CsCl, HCN channel blocker, 100 mM, 50 nl) into NG increased bradycardia and depressor responses to the ADN stimulation (Figure 1⇓). We conclude that elevated endogenous Angiotensin II in nodose ganglia contributes to the blunted baroreflex sensitivity in DM1 rodent model through the activation of HCN channels.
This research has received full or partial funding support from the American Heart Association, AHA National Center.