Altered Inflammatory Response Is Associated With an Impaired Autonomic Input to the Bone Marrow in the Spontaneously Hypertensive Rat

Zubcevic, Jasenka, et al. "Altered Inflammatory Response Is Associated With an Impaired Autonomic Input to the Bone Marrow in the Spontaneously Hypertensive Rat." Hypertension (2013): HYPERTENSIONAHA-113. This study was interested in the relationship between the immune system and cardiovascular disease, which they examined through the comparison of spontaneous hypertensive rats (SHR) and wild type Wistar-Kyoto Rats (WKY). They hypothesized that SHR would exhibit autonomic and endothelial dysfunctions, including increased inflammatory responses. Differences in femoral sympathetic nerve activity (fSNA) (innervation of bone marrow [BM]), alpha2a/beta2-adrenergic receptor expression, BM norepinephrine, BM imflammatory cells (ICs), edothelial progenitor cells (EPCs), and in vivo activity of the hypothalamic paraventricular nucleus (PVN)using MeMRI and GFP-pseudorabies virus (PRV)retrograde tracing. It is known that sympathetic drive in rats peaks at approximately 8pm and drops to its lowest levels around 11am, so most factors were measured both during the day and at night to review any possible changes in circadian-related sympathetic drive. Following the studies it was found that fSNA was increased 80% at night in the SHR compared to the WKY. There was also increased BM Nor and BM ICs during both the day and night in SHRs compared to WKY. Contrarily, BM EPCs were seen to decrease in SHR compared to WKY both during the day and night. However, blood ICs and blood EPCs were not seen to change from day to night time levels in the SHRs. Based upon the fact that IC's are known to compromise vascular integrity and EPCs are known to repair vascular damage, these results are conclusive with the hypothesis made. In order to compare sympathetic to parasympathetic drive in these animals levels of acetylcholine transferase and acetylcholine esterase were also measured showing decreases in both enzymes in the SHR population compared to the WKYs, insinuating a disregulation of sympathetic to parasympathetic drive. To support this, levels of fSNA were found to be significantly higher (25%)in SHR compared to normotensive control rats. Finally, both MeMRI and PRV retrograde tracing both revealed increased levels of in vivo neuronal activity of the PVN in SHRs compared to WKYs. Conclusively, this study showed an improper circadian-related balance between sympathetic and parasympathetic drive to immune organs (BM) that may be playing a role in perpetuating neurogenic hypertension. ~JI