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Indoleamine‐2,3‐Dioxygenase Restrains Hypertension Induced by Angiotensin II in Rats Fed a High Salt Diet
Author(s) -
Yiew Kan Hui Nicole,
Yoon Sook Kyung,
Huang Lei,
Jin Chunhua,
Mellor Andrew L.,
Pollock David M.
Publication year - 2013
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.27.1_supplement.1115.2
Subject(s) - medicine , endocrinology , kynurenine pathway , angiotensin ii , kynurenine , pathogenesis , excretion , inflammation , blood pressure , renin–angiotensin system , effector , chemistry , indoleamine 2,3 dioxygenase , limiting , tryptophan , biochemistry , amino acid , mechanical engineering , engineering
Inflammation and T‐cell activation has been shown to contribute to the pathogenesis of angiotensin II (AngII) dependent hypertension. Indoleamine‐2,3‐dioxygenase (IDO), the rate‐limiting enzyme involved in the degradation of tryptophan (TRP) to kynurenine (KYN), has a central role in increasing T regulatory cells and decreasing T effector cells. In this study, we examined the role of the IDO pathway in the hypertensive response to chronic AngII infusion in rats fed a high salt diet (HS; 4%NaCl). We hypothesized that inhibiting IDO with 1‐Methyl‐D‐Tryptophan (1‐MT) will exacerbate hypertension in this model due to loss of IDO‐mediated suppression of inflammation and T effector cells. To test our hypothesis, we administered 150 ng/kg/min Ang‐II (osmotic minipump) to male Sprague‐Dawley rats fed a 4% HS chow for two weeks. After two weeks of treatment, 1‐MT had no effect on MAP in control groups on either a normal salt (110 ± 3 mmHg) or HS (112 ± 2 mmHg) diet. Interestingly, 1‐MT significantly exacerbated MAP in Ang II/HS hypertensive rats (146 ± 4 mmHg vs. 161 ± 5 mmHg; p<0.05). There were no differences in food and water intake or in urinary protein and creatinine excretion among groups. These findings support the hypothesis that IDO activity contributes to blood pressure regulation by limiting Ang‐II dependent hypertension.