Sustained activation of the central baroreceptor pathway in angiotensin hypertension.

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed in angiotensin (Ang II) hypertension and that baroreflexes play a critical role in mediating this response. To support these findings, we determined whether the hypertension associated with chronic infusion of Ang II at 4.8 pmol/kg per minute (5ng/kg per minute) produces sustained activation of medullary neurons that participate in the central baroreceptor reflex pathway. We used Fos-like (Fos-Li) protein immunohistochemical methods to determine activation of neurons in the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM). Results were compared in three groups of chronically instrumented dogs subjected to infusion of: 1) saline (control); 2) Ang II-2 hours (acute); and 3) Ang II-5 days (chronic). Mean arterial pressure increased 22 +/- 3 and 35 +/- 3 mm Hg during acute and chronic Ang II infusion, respectively. There was little Fos-Li immunoreactivity in medullary neurons in control dogs. In contrast, during acute Ang II infusion there was a 2- to 3-fold increase in Fos-Li staining in the NTS and CVLM, but no increase in staining in RVLM neurons. As baroreceptor suppression of sympathoexcitatory cells in the RVLM is mediated by activation of neurons in the NTS and CVLM, these results were expected. More importantly, this same pattern of central neuronal activation was observed during chronic Ang II hypertension. Therefore, these results support recent findings indicating that baroreflex suppression of renal sympathetic nerve activity is a long-term compensatory response in Ang II hypertension.