Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome
- 1 May 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 53 (5), 767-774
- https://doi.org/10.1161/hypertensionaha.108.127357
Abstract
Postural tachycardia syndrome (POTS) is associated with increased plasma angiotensin II (Ang II). Ang II administered in the presence of NO synthase inhibition with nitro- l -arginine (NLA) and Ang II type 1 receptor blockade with losartan produces vasodilation during local heating in controls. We tested whether this angiotensin-mediated vasodilation occurs in POTS and whether it is related to angiotensin-converting enzyme 2 (ACE2) and Ang-(1-7). We used local cutaneous heating to 42°C and laser Doppler Flowmetry to assess NO-dependent conductance at 4 calf sites in 12 low-flow POTS and in 12 control subjects 17.6 to 25.5 years of age. We perfused Ringer’s solution through intradermal microdialysis catheters and performed local heating. We perfused one catheter with NLA (10 mmol/L)+losartan (2 μg/L) and repeated heating, and NLA+losartan+Ang II (10 μmol/L), repeating heating a third time. A second catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+DX600 (1 mmol/L; a selective ACE2 inhibitor), and reheated. A third catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+Ang-(1-7) (100 μmol/L), and reheated. The fourth catheter received Ang-(1-7) then reheated a second time only. Angiotensin-mediated vasodilation was present in control but not POTS. Ang-mediated dilation was eliminated by DX600, indicating an ACE2-related effect. Ang-mediated vasodilation was restored in POTS by Ang-(1-7). When administered alone during locally mediated heating, Ang-(1-7) improved the NO-dependent local heating response. ACE2 effects are blunted in low-flow POTS and restored by the ACE2 product Ang-(1-7). Data imply impaired catabolism of Ang II through the ACE2 pathway. Vasoconstriction in POTS may result from a reduction in Ang-(1-7) and an increase in Ang II.Keywords
This publication has 47 references indexed in Scilit:
- Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating responseAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- The human cutaneous circulation as a model of generalized microvascular functionJournal of Applied Physiology, 2008
- Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndromeAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Reduced body mass index is associated with increased angiotensin II in young women with postural tachycardia syndromeClinical Science, 2007
- Emerging Evidence for a Functional Angiotensin-Converting Enzyme 2-Angiotensin-(1-7)-Mas Receptor AxisHypertension, 2007
- Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humansAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Localization of the Renin–Angiotensin System Components to the Skeletal Muscle MicrocirculationMicrocirculation, 2005
- Angiotensin-(1–7) Is a Modulator of the Human Renin-Angiotensin SystemHypertension, 1999
- Converting enzyme activity and angiotensin metabolism in the dog brainstem.Hypertension, 1988
- Crossover design to test antihypertensive drugs with self-recorded blood pressure.Hypertension, 1988