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Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension.
. 2009 Mar; 296(3):H833-9.

Abstract

Insulin activation of the phosphatidylinositol 3-kinase (PI3K) pathway stimulates glucose uptake in peripheral tissues and synthesis of nitric oxide (NO) in the endothelium. Insulin resistance (IR) and hypertension frequently coexist, particularly among individuals with salt-sensitive hypertension. The mechanisms underlying this association are poorly understood. We investigated these mechanisms in a model of salt-sensitive hypertension in which we have previously shown that endothelial dysfunction is mediated by superoxide anion (O(2)(-)) linked to local ANG II. Dahl salt-sensitive rats were fed, for 6 wk, a normal salt diet (NS; 0.5% NaCl), high-salt diet (HS; 4% NaCl), HS plus the ANG II type 1 receptor (AT(1)R) blocker (ARB) candesartan (10 mg.kg(-1).day(-1)), or HS plus the antioxidant tempol (172 mg/l in drinking water). Hypertensive (mean arterial pressure: 145 +/- 4 vs. 102 +/- 5 mmHg in NS, P < 0.05) rats manifested increased aortic AT(1)R mRNA (210%) and protein (101%) expression and O(2)(-) production (104%) and impaired endothelium-dependent relaxation (EDR) to acetylcholine [maximal response (E(max)): 68 +/- 9 vs. 91 +/- 8% in NS, P < 0.05]. ARB or tempol normalized O(2)(-) and EDR despite that they did not normalize mean arterial pressure, which was reduced only 25%. Hypertensive rats manifested metabolic IR (36% reduction in the glucose infusion rate by insulin clamp), impaired NO-mediated insulin-induced EDR (E(max): 12 +/- 5 vs. 32 +/- 4% in NS, P < 0.05), and impaired insulin activation of PI3K/endothelial NO synthase. ARB or tempol improved insulin-mediated EDR, PI3K, Akt/ endothelial NO synthase phosphorylation, and metabolic IR (all P < 0.05). This study provides insight into the mechanisms that underlie the association between metabolic and hypertensive cardiovascular diseases and support the notion that O(2)(-) overproduction linked to tissue ANG II interferes with shared insulin signaling pathways in metabolic and cardiovascular tissues.

Authors+Show Affiliations

Nephrology-Hypertension Sect., Veterans Affairs Medical Center, and Vascular Biology Institute, Miller School of Medicine, Univ. of Miami, 1201 NW 16th St., Rm. A-1009, Miami, FL 33125, USA. mzhou2@med.miami.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19151253

Citation

Zhou, Ming-Sheng, et al. "Role of Angiotensin II and Oxidative Stress in Vascular Insulin Resistance Linked to Hypertension." American Journal of Physiology. Heart and Circulatory Physiology, vol. 296, no. 3, 2009, pp. H833-9.
Zhou MS, Schulman IH, Raij L. Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension. Am J Physiol Heart Circ Physiol. 2009;296(3):H833-9.
Zhou, M. S., Schulman, I. H., & Raij, L. (2009). Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension. American Journal of Physiology. Heart and Circulatory Physiology, 296(3), H833-9. https://doi.org/10.1152/ajpheart.01096.2008
Zhou MS, Schulman IH, Raij L. Role of Angiotensin II and Oxidative Stress in Vascular Insulin Resistance Linked to Hypertension. Am J Physiol Heart Circ Physiol. 2009;296(3):H833-9. PubMed PMID: 19151253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension. AU - Zhou,Ming-Sheng, AU - Schulman,Ivonne Hernandez, AU - Raij,Leopoldo, Y1 - 2009/01/16/ PY - 2009/1/20/entrez PY - 2009/1/20/pubmed PY - 2009/4/10/medline SP - H833 EP - 9 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 296 IS - 3 N2 - Insulin activation of the phosphatidylinositol 3-kinase (PI3K) pathway stimulates glucose uptake in peripheral tissues and synthesis of nitric oxide (NO) in the endothelium. Insulin resistance (IR) and hypertension frequently coexist, particularly among individuals with salt-sensitive hypertension. The mechanisms underlying this association are poorly understood. We investigated these mechanisms in a model of salt-sensitive hypertension in which we have previously shown that endothelial dysfunction is mediated by superoxide anion (O(2)(-)) linked to local ANG II. Dahl salt-sensitive rats were fed, for 6 wk, a normal salt diet (NS; 0.5% NaCl), high-salt diet (HS; 4% NaCl), HS plus the ANG II type 1 receptor (AT(1)R) blocker (ARB) candesartan (10 mg.kg(-1).day(-1)), or HS plus the antioxidant tempol (172 mg/l in drinking water). Hypertensive (mean arterial pressure: 145 +/- 4 vs. 102 +/- 5 mmHg in NS, P < 0.05) rats manifested increased aortic AT(1)R mRNA (210%) and protein (101%) expression and O(2)(-) production (104%) and impaired endothelium-dependent relaxation (EDR) to acetylcholine [maximal response (E(max)): 68 +/- 9 vs. 91 +/- 8% in NS, P < 0.05]. ARB or tempol normalized O(2)(-) and EDR despite that they did not normalize mean arterial pressure, which was reduced only 25%. Hypertensive rats manifested metabolic IR (36% reduction in the glucose infusion rate by insulin clamp), impaired NO-mediated insulin-induced EDR (E(max): 12 +/- 5 vs. 32 +/- 4% in NS, P < 0.05), and impaired insulin activation of PI3K/endothelial NO synthase. ARB or tempol improved insulin-mediated EDR, PI3K, Akt/ endothelial NO synthase phosphorylation, and metabolic IR (all P < 0.05). This study provides insight into the mechanisms that underlie the association between metabolic and hypertensive cardiovascular diseases and support the notion that O(2)(-) overproduction linked to tissue ANG II interferes with shared insulin signaling pathways in metabolic and cardiovascular tissues. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/19151253/Role_of_angiotensin_II_and_oxidative_stress_in_vascular_insulin_resistance_linked_to_hypertension_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.01096.2008?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -