Abstract The Milan hypertensive strain (MHS) rats are a genetic model of hypertension with adducin gene polymorphisms linked to enhanced renal tubular Na + reabsorption. Recently we demonstrated that Ca 2+ signaling is augmented in freshly isolated mesenteric artery myocytes from MHS rats. This is associated with greatly enhanced expression of Na + /Ca 2+ exchanger-1 (NCX1), C-type transient receptor potential (TRPC6) protein, and sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2) compared with arteries from Milan normotensive strain (MNS) rats. Here, we test the hypothesis that the enhanced Ca 2+ signaling in MHS arterial smooth muscle is directly reflected in augmented vasoconstriction (myogenic and phenylephrine (PE)-evoked responses) in isolated mesenteric small arteries. Systolic blood pressure was higher in MHS (145 ± 1 mmHg) than in MNS (112 ± 1 mmHg; P < 0.001; n = 16 each) rats. Pressurized mesenteric resistance arteries from MHS rats had significantly augmented myogenic tone and reactivity and enhanced constriction to low-dose (1–100 nM) PE. Isolated MHS arterial myocytes exhibited approximately twofold increased peak Ca 2+ signals in response to 5 μM PE or ATP in the absence and presence of extracellular Ca 2+ . These augmented responses are consistent with increased vasoconstrictor-evoked sarcoplasmic reticulum (SR) Ca 2+ release and increased Ca 2+ entry, respectively. The increased SR Ca 2+ release correlates with a doubling of inositol 1,4,5-trisphosphate receptor type 1 and tripling of SERCA2 expression. Pressurized MHS arteries also exhibited a ∼70% increase in 100 nM ouabain-induced vasoconstriction compared with MNS arteries. These functional alterations reveal that, in a genetic model of hypertension linked to renal dysfunction, multiple mechanisms within the arterial myocytes contribute to enhanced Ca 2+ signaling and myogenic and vasoconstrictor-induced arterial constriction. MHS rats have elevated plasma levels of endogenous ouabain, which may initiate the protein upregulation and enhanced Ca 2+ signaling. These molecular and functional changes provide a mechanism for the increased peripheral vascular resistance (whole body autoregulation) that underlies the sustained hypertension. adducin ouabain myogenic tone hypertension Milan normotensive rats Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print December 2011 , doi: 10.​1152/​ajpheart.​00950.​2011 AJP - Heart February 2012 vol. 302 no. 3 H611-H620 » Abstract Free Full Text Full Text (PDF) All Versions of this Article: ajpheart.00950.2011v1 302/3/H611 most recent Classifications Vascular Biology and Microcirculation Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Linde, C. I. Articles by Golovina, V. A. PubMed PubMed citation Articles by Linde, C. I. Articles by Golovina, V. A. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Heart About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6135 Online ISSN: 1522-1539 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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