Vascular remodeling in experimental hypertension.

The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole) vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts) and noncellular (extracellular matrix) components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation.

OBJECTIVE: We investigated whether angiotensin II (Ang II)-induced reactive oxygen species (ROS) generation is altered in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) during the phases of prehypertension, developing hypertension, and established hypertension and assessed the putative role of insulinlike growth factor-1 receptor (IGF-1R) in Ang II-mediated actions. METHODS: The VSMCs from SHR and Wistar-Kyoto rats (WKY) aged 4 (prehypertensive), 9 (developing hypertension), and 16 (established hypertension) weeks were studied. The ROS production and NAD(P)H oxidase activation were determined by fluorescence and chemiluminescence, respectively. The role of IGF-1R was assessed with the selective inhibitor AG1024. The ROS bioavailability was manipulated with Tiron (10(-5) mol/L) and diphenylene iodonium (DPI) (10(-6) mol/L). RESULTS: Angiotensin II dose dependently increased ROS production in WKY and SHR at all ages. The Ang II-induced responses were greater in SHR versus WKY at 9 and 16 weeks (P < .05). The Ang II-stimulated ROS increase was greater in 9- and 16-week-old SHR versus 4-week SHR (P < .05). These effects were reduced by AG 1024. Basal NAD(P)H oxidase activity was higher in VSMCs from 9-week-old SHR versus 4-week-old rats (P < .05). Angiotensin II induced a significant increase in oxidase activity in VSMCs from 9- and 16-week-old SHR (P < .001), without influencing responses in cells from 4-week-old SHR. Pretreatment of 9- and 16-week-old SHR cells with AG1024 reduced Ang II-mediated NAD(P)H oxidase activation (P < .05). CONCLUSIONS: Basal and Ang II-induced NAD(P)H-driven ROS generation are enhanced in VSMCs from SHR during development of hypertension, but not in cells from prehypertensive rats. Transactivation of IGF-1R by Ang II may be important in vascular oxidative excess in the development of hypertension in SHR.

Proliferación de células musculares lisas vasculares de ratas intolerantes a la glucosa / Vascular smooth muscle cells proliferation in rats with glucose intolerance

El síndrome X se caracteriza principalmente por resistencia a la insulina e hipertensión arterial (HTA). En un modelo experimental que reproduce esta situación patológica (ratas con sobrecarga crónica de fructosa [FFR] se examinó la respuesta proliferativa de células musculares lisas vasculares (cMLV) en cultivo de aorta y vasos mesentéricos a suero fetal bovino al 10 por ciento e insulina (100 µU/ml), por incorporación de [üH]-timidina, y se estudiaron los receptores para IGF-1. El grupo FFR desarrolló intolerancia a la glucosa e HTA con hipertrofia cardíaca. Las cMLV en cultivo mostraron mayor proliferación frente a un estímulo inespecífico como SFB 10 por ciento, pero no frente a la insulina, lo cual coincidió con disminución en el número de receptores para IGF-1. Estas observaciones podrían contribuir a la explicación de los mecanismos involucrados en las alteraciones cardiovasculares asociadas con insulinorresistencia

Proliferación de células musculares lisas vasculares de ratas intolerantes a la glucosa / Vascular smooth muscle cells proliferation in rats with glucose intolerance

El síndrome X se caracteriza principalmente por resistencia a la insulina e hipertensión arterial (HTA). En un modelo experimental que reproduce esta situación patológica (ratas con sobrecarga crónica de fructosa [FFR] se examinó la respuesta proliferativa de células musculares lisas vasculares (cMLV) en cultivo de aorta y vasos mesentéricos a suero fetal bovino al 10 por ciento e insulina (100 AU/ml), por incorporación de [³H]-timidina, y se estudiaron los receptores para IGF-1. El grupo FFR desarrolló intolerancia a la glucosa e HTA con hipertrofia cardíaca. Las cMLV en cultivo mostraron mayor proliferación frente a un estímulo inespecífico como SFB 10 por ciento, pero no frente a la insulina, lo cual coincidió con disminución en el número de receptores para IGF-1. Estas observaciones podrían contribuir a la explicación de los mecanismos involucrados en las alteraciones cardiovasculares asociadas con insulinorresistencia (AU)