Functional sympatholysis is impaired in hypertensive humans
Article first published online: 25 FEB 2011
© 2011 The Authors. Journal compilation © 2011 The Physiological Society
The Journal of Physiology
Volume 589, Issue 5, pages 1209–1220, March 2011
How to Cite
Vongpatanasin, W., Wang, Z., Arbique, D., Arbique, G., Adams-Huet, B., Mitchell, J. H., Victor, R. G. and Thomas, G. D. (2011), Functional sympatholysis is impaired in hypertensive humans. The Journal of Physiology, 589: 1209–1220. doi: 10.1113/jphysiol.2010.203026
- Issue published online: 25 FEB 2011
- Article first published online: 25 FEB 2011
- (Received 26 November 2010; accepted after revision 29 December 2010; first published online 4 January 2011)
Non-technical summary In healthy individuals, blunting of the vasoconstriction caused by activation of the sympathetic nervous system is thought to be an important mechanism that optimizes blood flow to the working muscles. We show for the first time that this protective mechanism, called functional sympatholysis, is impaired in middle-aged patients with high blood pressure. We also show that this impairment can be reversed by treatment with an angiotensin receptor blocker, but not with a thiazide-type diuretic. These findings indicate that angiotensin II may augment sympathetic vasoconstriction in the active muscles of hypertensive humans, which may explain the exaggerated rise in blood pressure and blunted decline in systemic vascular resistance during exercise in this population.
Abstract 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.