Functional sympatholysis is impaired in hypertensive humans

Wanpen Vongpatanasin, Zhongyun Wang, Debbie Arbique, Gary Arbique, Beverley Adams-Huet, Jere H. Mitchell, Ronald G. Victor, Gail D. Thomas

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97 Scopus citations


In healthy individuals, sympathetic vasoconstriction is markedly blunted in exercising muscles to optimize blood flow to the metabolically active muscle fibres. This protective mechanism, termed functional sympatholysis, is impaired in rat models of angiotensin-dependent hypertension. However, the relevance of these findings to human hypertension is unknown. Therefore, in 13 hypertensive and 17 normotensive subjects we measured muscle oxygenation and forearm blood flow (FBF) responses to reflex increases in sympathetic nerve activity (SNA) evoked by lower body negative pressure (LBNP) at rest and during moderate-intensity rhythmic handgrip exercise. In the normotensives, LBNP caused decreases in oxygenation and FBF (-16 ± 2% and -23 ± 4%, respectively) in resting forearm but not in exercising forearm (-1 ± 2% and -1 ± 3%, respectively; P < 0.05 vs. rest). In the hypertensives, LBNP evoked decreases in oxygenation and FBF that were similar in the resting and exercising forearm (-14 ± 2%vs.-12 ± 2% and -20 ± 3%vs.-13 ± 2%, respectively; P > 0.05), indicating impaired functional sympatholysis. In the hypertensives, SNA was unexpectedly increased by 54 ± 11% during handgrip alone. However, when SNA was experimentally increased during exercise in the normotensives, sympatholysis was unaffected. Treatment for 4 weeks with the angiotensin receptor blocker irbesartan, but not with the thiazide-type diuretic chlorthalidone, restored sympatholysis in the hypertensives. These data provide the first evidence that functional sympatholysis is impaired in hypertensive humans by a mechanism that appears to involve an angiotensin-dependent increase in sympathetic vasoconstriction in the exercising muscles.

Original languageEnglish (US)
Pages (from-to)1209-1220
Number of pages12
JournalJournal of Physiology
Issue number5
StatePublished - Mar 2011

All Science Journal Classification (ASJC) codes

  • Physiology


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