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Chronic early life stress induces alpha 1‐adrenergic receptor (α 1 ‐AR) desensitization in the renal vasculature
Author(s) -
Evans Logan,
Castillo Christopher,
Mahanes Timothy,
Osborn Jeffrey,
Loria Analia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.808.16
Subject(s) - renal cortex , endocrinology , medicine , prazosin , renal blood flow , phentolamine , chemistry , stimulation , receptor , kidney , renal function , microdialysis , renal circulation , antagonist , central nervous system
We have demonstrated that maternal separation (MS), a model of early life stress, induces a renal nerve‐dependent reduction in glomerular filtration rate. The aim of the present study was to investigate the role of the α 1‐ ARs in renal vasculature and cortex after MS (day 2‐14 life, 3 hr/day). Tissue from adult male MS and control rats was flash frozen for α 1‐ AR binding receptor assays and RT‐PCR. Renal vasculature and cortex were homogenized for obtaining membrane preparations. Tissues were incubated with [ 3 H]prazosin (2‐12 nM) in the presence or absence of phentolamine (50 μM). Bound and free ligands were separated using a tissue harvester. Renal cortical B max of α 1‐ ARs was not different between MS and C groups (40±7 vs. 47±8 fmol/mg protein; Kd 93±16 vs. 116±22 pM); however, renal vascular B max of α 1‐ ARs was reduced in MS rats (4±1 vs. 39±8 mol/mg protein, p<0.05; Kd 14±6 vs. 68±12 pM). α 1 ‐ARs mRNA correlated with receptor number in renal cortex, while mRNA was increased in all 3 α 1‐ AR subtypes in the vasculature from MS tissue compared to controls (p<0.05). Furthermore, renal nerve stimulation studies were conducted in anesthetized rats. Renal blood flow was measured while renal nerves were electrically stimulated at 1.5, 3.0, 4.0, and 6.0 Hz (1.0 ms; 1 ‐ 8 V). The constrictor responses were attenuated in MS vs. control rats (p<.0.05). These data support the existence of a mechanism of adrenergic desensitization in response to an increased sympathetic outflow to the kidney. The extent to which α 1 ‐adrenergic peripheral vascular desensitization occurs and the mechanisms involved in intact animals is the focus of ongoing studies. Funding: R00 HL111354