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O‐GlcNAc Transferase (OGT) Inhibition Does Not Improve Renal Artery Function in Male Angiotensin II Hypertensive Rats
Author(s) -
Rigsby Christine Spring,
Lima Victor V,
Webb R Clinton,
Tostes Rita C
Publication year - 2010
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.24.1_supplement.976.10
Subject(s) - transferase , angiotensin ii , pharmacology , renal function , renin–angiotensin system , endocrinology , chemistry , medicine , biochemistry , blood pressure , enzyme
Hypertension affects nearly two‐thirds of Americans and is highly associated with renal failure and enhanced sensitivity to vasoconstrictive agents, which has been linked to O‐GlcNAcylation. Previous studies from our laboratory indicate O‐GlcNAc expression is increased in arteries from hypertensive rats. Increasing O‐GlcNAc, using PUGNAc (OGA inhibitor), in non‐treated renal arteries leads to enhanced constriction. In renal arteries from angiotensin II (AngII)‐treated hypertensive rats, O‐GlcNAc expression is increased and arteries are more sensitive to phenylephrine (PE), indicated by a leftward shift ( Fig. A). We evaluated if a reduction in O‐GlcNAc, with OGT inhibition, in renal arteries from AngII‐treated rats would reduce sensitivity to PE. 9 week old male Wistar rats were treated with AngII (60ng/min; osmotic pump) for two weeks. Renal arteries were mounted in a myograph and incubated with ST045849 (10μM; OGT inhibitor) or vehicle (Veh; DMSO) for 30 mins. Concentration response curves (0.1nM – 0.1mM) to acetylcholine (ACh) and PE were constructed. There was no change in response to PE in ST045849‐treated arteries from AngII rats ( Fig. B). Surprisingly, there was decreased sensitivity to ACh in ST045849‐treated arteries (p<0.05; −6.9 ± 0.2 Veh vs. −6.3 ± 0.1 AngII –LogEC50). Therefore, we conclude that OGT inhibition does not improve renal artery function in AngII‐treated rats. (Support: NIH)