Abstract 035: Differential Sodium-evoked Activation of Pvn Magnocellular vs. Parvocellular Neurons in Rats Lacking Central GαI<SUB.2 Proteins Contributes to Sustained Elevations in Blood Pressure
Aim: To determine the role of brain Gαi2 proteins in mediating sodium-evoked PVN neuronal activation and blood pressure regulation in conscious rats.
Methods: 24-h intracerebroventricular scrambled (SCR) or Gαi2 oligodeoxynucleotide (ODN; 25μg/5μl)-pretreated conscious Sprague-Dawley rats were monitored for changes in MAP in response to HS (IV 3M NaCl; 0.14 ml/100g). Rats were sacrificed at control (C), 10, 40, or 100-min post-HS for PVN cFos IHC and analysis of plasma AVP and NE. Separate groups received a V1a receptor antagonist (IV; 10 μg/ml/kg) 5-min prior to HS.
Results: No difference was observed in sodium-evoked peak change in MAP and MAP remained elevated at 100-min in Gαi2 but not SCR ODN rats (MAP 100-min post-HS [mmHg] SCR 134±2 vs Gαi2 146±3, P<0.05). Significant increases in the number of Fos+ PVN magnocellular neurons were observed post-HS in SCR and Gαi2ODN groups ([Fos+ cells] SCR C 3±1 vs 100-min 31±5; Gαi2C 2±0 vs 100-min 26±4, P<0.05). A rapid increase in circulating AVP was observed at 10-min in both SCR (plasma AVP [pg/mL] C 12.2±1.6 vs 10-min 62.8±6.9, P<0.05) and Gαi2ODN (plasma AVP [pg/mL] C 12.1±1.5 vs 10-min 67.7±7.7 P<0.05) groups and returned to control levels at 40- and 100-min. SCR ODN rats exhibited significant increases in the number of Fos+ PVN parvocellular neurons ([Fos+ cells] C 15±1 vs 100-min 67±4, P<0.05) and a significant suppression in circulating NE post-HS (plasma NE [nmol/L] C 44.1±4.9 vs 10-min 17.4±3.9, P<0.05). Gαi2ODN rats exhibited significantly less Fos+ parvocellular neurons compared to SCR ODN rats (100-min [Fos+ cells] SCR 67±4 vs Gαi2 30±2, P<0.05) and failed to suppress circulating NE (P>0.05). V1a receptor blockade prevented a HS-evoked increase in MAP in SCR ODN rats while Gαi2ODN rats exhibited elevated MAP (MAP 100-min [mmHg] SCR 125±2 vs Gαi2 135±0, P <0.05).
Conclusion: Brain Gαi2 proteins are required to mediate sodium-evoked parvocellular sympathetic, but not magnocellular vasopressinergic, responses to maintain physiological blood pressure regulation. A significant component of blood pressure control in this setting is regulated by the sympathetic nervous system, as supported by the attenuated activation of PVN parvocellular neurons and a failure to suppress circulating levels of NE in Gαi2 ODN rats.
Author Disclosures: C.Y. Carmichael: None. R.D. Wainford: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; RO1 HL107330, K02HL112718.
- © 2015 by American Heart Association, Inc.