Dehydration switches emphasis from hypothalamus to medulla oblongata for maintenance of sympathetic nerve activity (SNA)

Abstract

The mechanisms underlying the increase in SNA after dehydration are not fully established. In the present study, we investigated the sequential effects of systemic administration of Losartan (20 μM, AT1 receptor antagonist), brain transections and inhibition of commissural nucleus tractus solitarii (cNTS) on ongoing thoracic SNA after water deprivation for 3 days. Male Wistar rats (65‐85 g) were decorticated to make insentient and perfused intra‐arterially. In euhydrated (EH) rats (290 mOsmol perfusate, n=5), systemic application of Losartan and subsequent pre‐collicular transection (to remove the hypothalamus) reduced SNA by ‐20 ± 3% and ‐44 ± 2% relative to baseline respectively. In contrast, in 3 day dehydrated (DH) rats (340 mOsmol perfusate, n=6) Losartan, subsequent pre‐collicular and pontine transections failed to reduce SNA (‐1 ± 4%, ‐3 ± 8% and ‐12 ± 4% respectively). However, transection at the medulla‐spinal cord junction reduced SNA by ‐70±8%. In intact DH, but not EH rats, reversible inactivation of cNTS using isoguvacine, (a GABAA receptor agonist; 100 mM, 100 nl), reduced significantly baseline SNA (‐33 ± 7% vs 3 ± 8% in EH). These data indicate that in the EH rat baseline SNA is dependent on both the hypothalamus and AT1 receptors. Following chronic dehydration, the regulation of SNA transfers to the medulla oblongata, particularly cNTS. Funded by CNPq and CAPES (Brazil), The Royal Society.