Abstract 518: Vascular Smooth Muscle Na/Ca exchanger-1 (NCX1) Regulates Basal Blood Pressure and Angiotensin II-induced Hypertension
We have reported that vascular smooth muscle (VSM)-specific NCX1 overexpression exaggerated blood pressure (BP) elevation induced by acute Angiotensin II (Ang II) injection. Here, we aimed to study if altered VSM NCX1 expression affects chronic Ang II infusion-induced hypertension. Adult wild type (WT) and transgenic mice that express either ∼7 fold higher (TG) or ∼90% lower (KO) VSM NCX1 protein were used. Mice of each genotype were randomly divided into vehicle and Ang II groups, to which physiological saline or 400 ng/kg/min Ang II in saline were given, respectively, by a subcutaneously embedded minipump. Three weeks later, BP was measured by intra-carotid artery catheter under 1.5% isoflurane anesthesia. Of the three vehicle groups, NCX TG mice had higher (108 ± 2 mm Hg, n = 7, P < 0.05), and KO mice had lower (88 ± 2 mm Hg, n = 8, P < 0.05), baseline BP compared to WT mice (97 ± 3 mm Hg, n = 5). Ang II treatment caused BP elevation to a significantly greater extent in TG (∼18 ± 2%, n = 7, P < 0.05) than in WT mice (∼10 ± 2%, n = 4), but had negligible effect on KO mice (∼6 ± 4%, n = 6, P > 0.05). NCX1 protein expression was upregulated by Ang II treatment in TG and WT (∼2 fold), but not KO, mouse aorta. We then investigated vasoconstriction in isolated, pressurized mesenteric small arteries. Basal myogenic tone (MT, 70 mm Hg) was augmented in TG (23 ± 2% of passive diameter, PD, n = 5, P < 0.05) and attenuated in KO (15 ± 1%, n = 8), compared to WT arteries (17 ± 2%, n = 5). Myogenic reactivity (MR) and vasoconstriction induced by phenyleprine (PE) were enhanced in TG and reduced in KO arteries. Ang II treatment potentiated MR/MT but not PE-induced vasoconstriction. We conclude that: 1) Under physiological conditions, in small resistance arteries that have tone, VSM NCX1 primarily mediates Ca2+ entry which contributes to the maintenance of vascular tone; and 2) The level of VSM NCX1 expression (function), arterial contraction, and BP are highly correlated under both physiological and certain hypertension conditions (e.g., salt-, Ang II-induced animal hypertension and human pulmonary hypertension). This indicates that NCX1 plays a critical role in the long-term control of arterial contractility and basal BP, and also might play an important role in most, if not all, forms of hypertension.
- © 2012 by American Heart Association, Inc.