Abstract
The hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-treated rabbits, the effects on blood pressure and tonic and reflex renal SNA (RSNA) of microinjecting into the PVN either RU28318 to block MR, losartan to block Ang (AT1) receptors or muscimol to inhibit GABAA receptor agonist actions. Male rabbits received a moderate dose of Ang II (24 ng/kg/min subcutaneously) for 3 months (n = 13) or sham treatment (n = 13). At 3 months, blood pressure increased by +19% in the Ang II group compared to 10% in the sham (P = 0.022) but RSNA was similar. RU28318 lowered blood pressure in both Ang II and shams but had a greater effect on RSNA and heart rate in the Ang II-treated group (P < 0.05). Losartan also lowered RSNA, while muscimol produced sympatho-excitation in both groups. In Ang II-treated rabbits, RU28318 attenuated the blood pressure increase following chemoreceptor stimulation but did not affect responses to air jet stress. In contrast losartan and muscimol reduced blood pressure and RSNA responses to both hypoxia and air jet. While neither RU28318 nor losartan changed the RSNA baroreflex, RU28318 augmented the range of the heart rate baroreflex by 10% in Ang II-treated rabbits. Muscimol, however, augmented the RSNA baroreflex by 11% in sham animals and none of the treatments altered baroreflex sensitivity. In conclusion, 3 months of moderate Ang II treatment promotes activation of reflex RSNA principally via MR activation in the PVN, rather than via activation of AT1 receptors. However, the onset of hypertension is independent of both. Interestingly, the sympatho-excitatory effects of muscimol in both groups suggest that overall, the PVN regulates a tonic sympatho-inhibitory influence on blood pressure control.
Highlights
The important contribution of an activated sympathetic nervous system (SNS) to hypertension is well established (Esler, 1995, 2015)
In the present study we examined whether the hypertension induced by long term infusion of low dose Ang II involved activation of mineralocorticoid receptors (MR) or AT1 receptors (AT1R) in the paraventricular nucleus (PVN) and modification of responses to baroreflexes, stress or chemoreceptor activation
The main findings (Table 4) were that blood pressure increased to a greater extent in the Ang II group compared to the sham group but renal SNA (RSNA) was similar
Summary
The important contribution of an activated sympathetic nervous system (SNS) to hypertension is well established (Esler, 1995, 2015). PVN neurons project to pre-sympathetic neurons in the spinal cord (Saper et al, 1976) and are prime candidates to mediate the sympatho-excitation observed with Ang II hypertension (Biancardi et al, 2014) This view is supported by studies showing knock down of AT1R only in the PVN prevents most of the increase in blood pressure (Chen A. et al, 2014). The aims of the present study were to determine, in conscious rabbits (1) whether low level activation of the RAAS modeled by infusion of a low dose of Ang II for 12 weeks causes sustained activation of neurons in the PVN resulting in amplified sympathetic and pressor responses to stress, chemoreceptor activation and hypertension and (2) whether the process involves increased MR and/or AT1R activation in the PVN. To determine the overall contribution of the PVN, we examined the effect of muscimol (Maiorov et al, 2000) as it provides neuronal inhibition via activation of GABAA receptors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
