title: 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.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
authors.forename: Magalie
authors.initials: M
authors.lastname: Pilon
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Julie-Emilie
authors.initials: JE
authors.lastname: Huot-Marchand
authors.forename: Denis
authors.initials: D
authors.lastname: deBlois
authors.forename: Jacques de
authors.initials: Jd
authors.lastname: Champlain
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture