Oral Presentation Neuropathophysiology - an ISH satellite 2012

Decreased respiratory modulation of sympathetic activity in the Spontaneously Hypertensive rat during silencing of catecholaminergic C1 neurons of the rostral ventrolateral medulla oblongata (#46)

Clement Menuet 1 , Angela Connelly 1 , Jaspreet K Bassi 1 , Andrew M Allen 1
  1. Department of Physiology, University of Melbourne, VIC, Australia

Background: Selective lesions of sympathoexcitatory catecholaminergic (C1) neurones of the rostral ventrolateral medulla oblongata (RVLM) induce a small decrease in blood pressure in normotensive rats. Selective, reversible inhibition of these neurons in the working-heart brainstem preparation (WHBP) also decreases the respiratory-related bursts of sympathetic nerve activity (SNA) and arterial blood pressure in normotensive rats. Since increased respiratory-related bursts of SNA are proposed to contribute to the development of hypertension in the Spontaneously Hypertensive (SH) rat, we investigated the effects of reversible inhibition of C1 neurones in SH and control Wistar-Kyoto (WKY) rats.

Methods: Lentiviral vectors, which were used to express the inhibitory Drosophila allatostatin receptor under the control of the PRSx8 promoter, were injected bilaterally into the RVLM of anesthetized, 21 day old, male SH and WKY rats. Ten days after injection, we used the WHBP to record perfusion pressure (PP), thoracic SNA and phrenic nerve activity (PNA) during perfusion with 1µM allatostatin.

Results: Whilst PNA was similar between SH and WKY rats, SH rats exhibited increased respiratory-related bursts of SNA, Traube-Hering waves and PP. Allatostatin didn’t affect PNA but markedly attenuated respiratory-related bursts of SNA without dramatically altering tonic SNA. Allatostatin decreased Traube-Hering waves and PP in both SH and WKY rats. All changes were reversed with washout of allatostatin.

Conclusion: C1 neurones are a key component of the central pathway transmitting respiratory modulation of sympathetic activity. As this modulation is increased in SH rats, targeting these cells might represent an efficient way to reduce, if not abolish, hypertension in the SH rat.

Disclosure: the authors declare no conflict of interest related to this work.