Journal
HYPERTENSION
Volume 53, Issue 5, Pages 767-774Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.108.127357
Keywords
angiotensin; lasers; autonomic nervous system
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Funding
- National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL074873, R01HL087803, R21HL091948]
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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 mu g/L) and repeated heating, and NLA + losartan + Ang II (10 mu mol/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 mu mol/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. (Hypertension. 2009; 53: 767-774.)
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