Abstract 21643: Impaired Functional Sympatholysis in Human Hypertension Is Mediated by Angiotensin II
In normal physiologic states, sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the working muscle. This protective adaptation known as functional sympatholysis was found to be impaired in rat models of angiotensin II (ANG II)-induced hypertension. However, the relevance of these findings has not been addressed in human hypertension. Accordingly, we assessed vasoconstrictor response in the forearms of 13 patients with untreated stage 1 essential hypertensive (HTN) and 15 normotensive (NT) subjects using near infrared spectroscopy and ultrasonography to measure changes in muscle oxygenation and forearm blood flow (FBF) induced by reflex sympathetic activation evoked by lower body negative pressure (LBNP). We found that, in the NT group, muscle oxygenation and FBF reduced by 16±2% and 23±4%, respectively, during LBNP in resting forearm but remained unchanged (−1±2% and −1±3%, respectively) in exercising forearm (p < 0.05 vs rest). In the HTN group, muscle oxygenation reduced similarly during LBNP in the resting and exercising forearm (14±2% versus 12±2%, p > 0.05). FBF and forearm vascular conductance (FVC) also reduced similarly during LBNP in the resting and exercising forearm. However, sympathetic nerve activity (SNA), assessed directly by intraneural microelectrodes, was significantly higher during rhythmic handgrip (RHG) alone and during RHG plus LBNP in the HTN group than the NT group. When LBNP was introduced to a subset of the NT group at an earlier onset and at the higher level of LBNP to mimic pattern of sympathetic activation in the HTN group, muscle oxygenation and FBF remained unaffected in the exercising muscle. Irbesartan reduced resting mean blood pressure (BP) by 9±3 mmHg but had no effect on SNA or muscle oxygenation, FBF, and FVC during LBNP in the resting forearm. However, irbesartan attenuated reduction in muscle oxygenation, FBF, and FVC during LBNP in the exercising forearm. This effect of irbesartan disappeared after washout period of 4 weeks. In summary, our data provide the first direct evidence for impaired functional sympatholysis in human hypertension and a strong support for the role of Ang II in modulating sympathetic vasoconstriction during exercise, independent of SNA.
- © 2010 by American Heart Association, Inc.