Effect of chronic inhibition of nitric oxide on hypertension, insulin resistance, and cardiovascular remodeling in glucose-fed rats.

Abstract

To determine the contribution of nitric oxide (NO) in cardiovascular remodeling associated to hypertension and insulin resistance, male Sprague-Dawley rats received tap water supplemented or not (control), with 10% D-glucose (G) and/or 50 mg x kg(-1) x d(-1) L-NAME to inhibit NO synthase (G-LN or LN) for 4 weeks. Systolic blood pressure increased by 12%, 26%, and 39% with G, LN, and G-LN treatments, respectively. Hyperinsulinemia and insulin resistance (homeostasis model assessment index) occurred in G-treated rats (P < 0.05) and were further increased in G-LN (P < 0.01). Plasma adrenaline concentrations were markedly increased in all treated groups, especially in G-LN (P < 0.01), whereas noradrenaline was increased in G-treated rats only. Whereas no cardiac hypertrophy or fibrosis was detected, aortic hypertrophy occurred in LN and G-LN rats (P < 0.001) without smooth muscle hyperplasia. Superoxide anion formation was increased in the aorta of all treated groups (P < 0.01) and in the heart of LN (P < 0.05), but reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity was not affected. In conclusion, the loss of the wide-range protective effects of NO, the increased vascular oxidative stress, and the sympathoadrenal hyperactivity are among the contributing factors leading to the exacerbation of hypertension and insulin resistance in G-LN. These factors were sufficient to cause vascular but not cardiac hypertrophy.

• Authors: Magalie Pilon, Rong Wu, Julie-Emilie Huot-Marchand, Denis deBlois, Jacques de Champlain, Réjean Couture
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 53 Issue 5 Pg. 405-13 (May 2009) ISSN: 1533-4023 [Electronic] United States
• PMID: 19333132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Superoxides
• Nitric Oxide
• Nitric Oxide Synthase
• Glucose
• NG-Nitroarginine Methyl Ester
• Norepinephrine
• Epinephrine

Topics

• Animals
• Aorta, Thoracic (metabolism, pathology)
• Blood Pressure (drug effects)
• Diet
• Epinephrine (blood)
• Glucose (administration & dosage, metabolism)
• Hypertension (metabolism, pathology, physiopathology)
• Hypertrophy
• Insulin Resistance
• Male
• Muscle, Smooth, Vascular (metabolism, pathology)
• Myocardium (metabolism, pathology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (antagonists & inhibitors)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Norepinephrine (blood)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Superoxides (metabolism)
• Ventricular Remodeling (physiology)