Abstract 400: Angiotensin II Triggers the Same Pressor Mechanisms in Salt-sensitive Hypertension and During Salt Depletion
2013
Salt restriction or blood volume decline activates the renin-angiotensin (Ang) system to protect against short- and long-term drops in blood pressure (BP). Excess dietary salt and salt retention, however, activates CNS Ang II-mediated mechanisms that elevate BP. We tested the idea that the same CNS-regulated downstream mechanisms modulate total peripheral vascular resistance (TPR) under both conditions. Protocol 1: normal Sprague-Dawley (SD) rats were fed either normal salt (NS, 0.4% NaCl) or low salt (LS, 0.1% NaCl) for 2 wks. Protocol 2: SD rats were infused subcutaneously with vehicle (V, saline) or Ang II (A, 150 ng/kg/min); some V and some A rats were fed NS, and the others were fed high salt (HS, 2% NaCl) for 2 wks. At the end of both protocols, intra-arterial BP was recorded and blood was drawn for endogenous ouabain (EO) determination by radioimmunoassay and multi-stage mass spectroscopy. Aortae and mesenteric arteries were harvested for protein immunoblots to determine arterial smooth muscle (ASM) expression of Na/Ca exchanger-1 (NCX1), a key Ca 2+ transporter. LS did not affect mean BP (87±2 vs 91±4 mm Hg, n =6 each), but did raise plasma EO (0.70±0.19 vs 0.21±0.02 nM, P 0.05) and increase ASM NCX1 expression 1.52-fold. Ang II infusion and, especially, HS + Ang II, increased mean BP (110±4 and 124±3 mm Hg, P P n =5-8) and plasma EO (0.53±0.31 and 1.31±0.72 nM, respectively, both P n =5-8). HS + Ang II also increased ASM NCX1 expression 1.91-fold. HS + Ang II, as well as LS also increased expression of SERCA2 and TRPC6, two other ASM Ca 2+ transporters. Intracerebroventricular Ang II also raises plasma EO and increases expression of the 3 Ca 2+ transporters in ASM; thus, the CNS controls this pressor pathway (Hamlyn et al., Hypertension 60 (3, Suppl.):e419, 2012). The new data reveal that both LS and HS activate the same downstream mechanisms: they elevate plasma EO and ASM Ca 2+ transporter expression. The increases in ASM Ca 2+ transporter expression, and enhanced sympathetic drive, should increase arterial tone and raise BP during salt excess, and minimize BP decline. We conclude that these fundamental mechanisms contribute to “whole body autoregulation” in the long-term control of TPR and BP.
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