Investigations regarding hypertension and dietary sodium, both factors that influence stroke risk, have previously been limited to using genetically disparate treatment and control groups, namely the stroke-prone, spontaneously hypertensive rat and Wistar-Kyoto rat. In this investigation, we have characterized and compared cerebral vasoactive system adaptations following stroke in genetically identical, salt-induced hypertensive, and normotensive control mice. Briefly, ANP+/− (C57BJ/6 × SV129 background) mice were fed chow containing either 0.8 % NaCl (NS) or 8.0 % NaCl (HS) for 7 weeks. Transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Infarct volumes were measured 24-h post-reperfusion and the mRNA expression of five major vasoactive systems was characterized using qPCR. Along with previous publications, our data validate a salt-induced hypertensive state in ANP+/− mice fed HS chow as they displayed left ventricular hypertrophy, increased systolic blood pressure, and increased urinary sodium excretion. Following MCAO, mice fed HS exhibited larger infarct volumes than their dietary counterparts. In addition, significant up-regulation in Et-1 and Nos3 mRNA expression in response to salt and stroke suggests implications with increased cerebral damage in this group. In conclusion, our data demonstrate increased cerebral susceptibility to stroke in salt-induced hypertensive mice. More importantly, however, we have characterized a novel method of investigating hypertension and stroke with the use of genetically identical treatment and control groups. This is the first investigation in which genetic confounding variables have been eliminated.
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The authors would like to thank Dr. Alastair Ferguson, Department of Biomedical and Molecular Sciences, Queen’s University, for the use of the CODA non-invasive tail-cuff BP system. NMV is a recipient of the Franklin Bracken Student Fellowship. Research equipment funding (real-time PCR) was provided by the Canadian Foundation of Innovation (CFI).
Elliott P, Stamler J, Nichols R et al (1996) Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. Intersalt Cooperative Research Group. BMJ 312:1249–1253PubMedCentralPubMedCrossRefGoogle Scholar
Fujii K, Weno BL, Baumbach GL, Heistad DD (1992) Effect of antihypertensive treatment on focal cerebral infarction. Hypertension 19:713–716PubMedCrossRefGoogle Scholar
John SW, Krege JH, Oliver PM et al (1995) Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science 267:679–681PubMedCrossRefGoogle Scholar
Sangaralingham SJ, Tse MY, Pang SC (2007) Estrogen protects against the development of salt-induced cardiac hypertrophy in heterozygous proANP gene-disrupted mice. J Endocrinol 194:143–152. doi:10.1677/JOE-07-0130PubMedCrossRefGoogle Scholar
Angelis E, Tse MY, Pang SC (2005) Interactions between atrial natriuretic peptide and the renin–angiotensin system during salt-sensitivity exhibited by the proANP gene-disrupted mouse. Mol Cell Biochem 276:121–131PubMedCrossRefGoogle Scholar
Armstrong DWJ, Tse MY, O’Tierney-Ginn PF et al (2013) Gestational hypertension in atrial natriuretic peptide knockout mice and the developmental origins of salt-sensitivity and cardiac hypertrophy. Regul Pept 186C:108–115. doi:10.1016/j.regpep.2013.08.006CrossRefGoogle Scholar
Huang Z, Huang PL, Panahian N et al (1994) Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265:1883–1885PubMedCrossRefGoogle Scholar
Lennmyr F, Ata KA, Funa K et al (1998) Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat. J Neuropathol Exp Neurol 57:874–882PubMedCrossRefGoogle Scholar