{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:46:41Z","timestamp":1792709201055,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,7,12]],"date-time":"2013-07-12T00:00:00Z","timestamp":1373587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Previously, we showed that <jats:italic>Gnasxl<\/jats:italic> knock\u2010out mice are lean and hypermetabolic, with increased sympathetic stimulation of adipose tissue. Do these mice also display elevated sympathetic cardiovascular tone? Is the brain glucagon\u2010like peptide\u20101 system involved?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p><jats:italic>Gnasxl<\/jats:italic> knock\u2010outs have increased blood pressure, heart rate and body temperature. Heart rate variability analysis suggests an elevated sympathetic tone. The sympatholytic reserpine had stronger effects on blood pressure, heart rate and heart rate variability in knock\u2010out compared with wild\u2010type mice. Stimulation of the glucagon\u2010like peptide\u20101 system inhibited parasympathetic tone to a similar extent in both genotypes, with a stronger associated increase in heart rate in knock\u2010outs. Deficiency of <jats:italic>Gnasxl<\/jats:italic> increases sympathetic cardiovascular tone.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Imbalances of energy homeostasis are often associated with cardiovascular complications. Previous work has shown that <jats:italic>Gnasxl<\/jats:italic>\u2010deficient mice have a lean and hypermetabolic phenotype, with increased sympathetic stimulation of adipose tissue. The <jats:italic>Gnasxl<\/jats:italic> transcript from the imprinted <jats:italic>Gnas<\/jats:italic> locus encodes the trimeric G\u2010protein subunit XL\u03b1s, which is expressed in brain regions that regulate energy homeostasis and sympathetic nervous system (SNS) activity. To determine whether <jats:italic>Gnasxl<\/jats:italic> knock\u2010out (KO) mice display additional SNS\u2010related phenotypes, we have now investigated the cardiovascular system. The <jats:italic>Gnasxl<\/jats:italic> KO mice were \u223c20 mmHg hypertensive in comparison to wild\u2010type (WT) littermates (<jats:italic>P<\/jats:italic>\u2264 0.05) and hypersensitive to the sympatholytic drug reserpine. Using telemetry, we detected an increased waking heart rate in conscious KOs (630 \u00b1 10 <jats:italic>versus<\/jats:italic> 584 \u00b1 12 beats min<jats:sup>\u22121<\/jats:sup>, KO <jats:italic>versus<\/jats:italic> WT, <jats:italic>P<\/jats:italic>\u2264 0.05). Body temperature was also elevated (38.1 \u00b1 0.3 <jats:italic>versus<\/jats:italic> 36.9 \u00b1 0.4\u00b0C, KO <jats:italic>versus<\/jats:italic> WT, <jats:italic>P<\/jats:italic>\u2264 0.05). To investigate autonomic nervous system influences, we used heart rate variability analyses. We empirically defined frequency power bands using atropine and reserpine and verified high\u2010frequency (HF) power and low\u2010frequency (LF) LF\/HF power ratio to be indicators of parasympathetic and sympathetic activity, respectively. The LF\/HF power ratio was greater in KOs and more sensitive to reserpine than in WTs, consistent with elevated SNS activity. In contrast, atropine and exendin\u20104, a centrally acting agonist of the glucagon\u2010like peptide\u20101 receptor, which influences cardiovascular physiology and metabolism, reduced HF power equally in both genotypes. This was associated with a greater increase in heart rate in KOs. Mild stress had a blunted effect on the LF\/HF ratio in KOs consistent with elevated basal sympathetic activity. We conclude that XL\u03b1s is required for the inhibition of sympathetic outflow towards cardiovascular and metabolically relevant tissues.<\/jats:p>","DOI":"10.1113\/expphysiol.2013.073064","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T00:46:32Z","timestamp":1370652392000},"page":"1432-1445","source":"Crossref","is-referenced-by-count":16,"title":["Elevated blood pressure, heart rate and body temperature in mice lacking the XL\u03b1s protein of the <i>Gnas<\/i> locus is due to increased sympathetic tone"],"prefix":"10.1113","volume":"98","author":[{"given":"Nicolas","family":"Nunn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire 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