A Single Angiotensin II Hypertensive Stimulus Is Associated with Prolonged Neuronal and Immune System Activation in Wistar-Kyoto Rats

作者：Zubcevic Jasenka; Santisteban Monica M; Perez Pablo D; Arocha Rebeca; Hiller Helmut; Malphurs Wendi L; Colon Perez Luis M; Sharma Ravindra K; de Kloet Annette; Krause Eric G; Febo Marcelo; Raizada Mohan K

来源：Frontiers in Physiology, 2017, 8: 592.

DOI：10.3389/fphys.2017.00592

• MRI
• hypertension
• inflammation mediators
• angiotensin II
• blood pressure
• ANS

Activation of autonomic neural pathways by chronic hypertensive stimuli plays a significant role in pathogenesis of hypertension. Here, we proposed that even a single acute hypertensive stimulus will activate neural and immune pathways that may be important in initiation of memory imprinting seen in chronic hypertension. We investigated the effects of acute angiotensin II (Ang II) administration on blood pressure, neural activation in cardioregulatory brain regions, and central and systemic immune responses, at 1 and 24 h post-injection. Administration of a single bolus intra-peritoneal (I.P.) injection of Ang II (36 mu g/kg) resulted in a transient increase in the mean arterial pressure (MAP) (by 22 +/- 4 mmHg vs saline), which returned to baseline within 1 h. However, in contrast to MAP, neuronal activity, as measured by manganese-enhanced magnetic resonance (MEMRI), remained elevated in several cardioregulatory brain regions over 24 h. The increase was predominant in autonomic regions, such as the subfornical organ (SFO; similar to 20%), paraventricular nucleus of the hypothalamus (PVN; similar to 20%) and rostral ventrolateral medulla (RVLM; similar to 900%), among others. Similarly, systemic and central immune responses, as evidenced by circulating levels of CD4(+)/IL17(+) T cells, and increased IL17 levels and activation of microglia in the PVN, respectively, remained elevated at 24 h following Ang II challenge. Elevated Fos expression in the PVN was also present at 24 h (by 73 +/- 11%) following Ang II compared to control saline injections, confirming persistent activation of PVN. Thus, even a single Ang II hypertensive stimulus will initiate changes in neuronal and immune cells that play a role in the developing hypertensive phenotype.

• 出版日期2017-8-31