Dept. of Integrative Physiology, Univ. of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
Am J Physiol Heart Circ Physiol. 2011 Jul;301(1):H230-40. Epub 2011 May 2.
Numerous elegant studies by Professor Alan Sved and other investigators have shown that elevated sympathetic nerve activity (in spontaneously hypertensive rats, Dahl salt-sensitive rats and other hypertenive rat models) is associated with increased tonic activation of RVLM by glutamate and angiotensin II and decreased tonic GABAergic inhibition. Obese Zucker rats (OZR) have elevated renal and splanchnic sympathetic nerve activity and mean arterial pressure, however the mechanisms are unknown. In order to understand the mechanisms the authors did mutliple experiments and made some significant findings. When RVLM was inhibited it produced a greater decrease in MAP in the OZR compared to their lean counterpart. When AT1 receptors were blocked it produced a modest decrease in splanchnic SNA and MAP in the OZR but not in lean zucker rats (LZR). Ionotropic glutamate receptor antagonists produced comparable differences in the SNA, MAP and HR in OZR and LZR. GABA-A receptor antagonist produced smaller increase in SNA, MAP and HR in OZR compared to LZR. Finally inhibition of CVLM or the NTS produced a smaller increase in SNA and HR in OZR compared to LZR but the pressor responses were normal. The authors suggest some possible explantion for this unexpected finding. One possibility is that the pressor response is a summation of changes in splanchnic SNA with other other sympathetic responses and another possibility could be related to a threshold effect because of changes in vascular reactivity. Overall the results suggest that elevated MAP and SNA in the OZRs are a measure of increased angiotensinergic activation and reduced GABAergic inhibition of the RVLM.
No comments:
Post a Comment