Abstract 17682: Angiotensin-(1-7) Inhibits Endothelin-1-Mediated Vasoconstriction but Does Not Affect Nitric Oxide-Dependent Vasodilation in Obese Patients
Obese patients have vascular dysfunction related to impaired vasodilator responsiveness and increased endothelin (ET)-1 vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the ACE2 product Ang-(1-7) exerts cardiovascular benefits through stimulation of the receptor Mas and improves insulin resistance in the skeletal muscle by microvascular recruiting. Here we tested the hypothesis that Ang-(1-7) might advantageously impact the nitric oxide (NO)-dependent vasodilation and the ET-1 system activity in 12 patients with central obesity (CO).
To this purpose, forearm blood flow (FBF) responses to intra-arterial infusion of graded doses of acetylcholine (ACh; stimulus for endothelial release of NO) and sodium nitroprusside (SNP; exogenous NO donor) were assessed by strain-gauge plethysmography during co-infusion of saline and following administration of Ang-(1-7) (10 nmol/min). No significant change, however, was observed in the vasodilator responses to ACh (P>0.05) and SNP (P>0.05) during infusion of Ang-(1-7). To investigate the bioactivity of the ET-1 system and the endogenous NO pathway, the hemodynamic reactivity to selective blockade of ETA receptors (BQ-123, 10 nmol/min for 60 min) followed by NO synthesis inhibition (L-NMMA, 4 μmol/min for 15 min) was assessed in the absence or the presence of Ang-(1-7). In the absence of Ang-(1-7), ETA receptor blockade induced a significant increased in FBF (88±17% [mean±SEM] at 60 min; P<0.001 vs. baseline), whereas Ang-(1-7) administration abrogated the vasodilator effect of BQ-123 almost completely (8±7%; P<0.001 vs. absence of Ang-(1-7)). The vasoconstrictor responses to NO inhibition by L-NMMA during ETA receptor blockade, however, were not significantly different before and after infusion of Ang-(1-7) (37±8% vs. 32±5%, respectively; P>0.05).
These findings indicate that Ang-(1-7) exerts favorable vascular effects in patients with CO by reducing ET-1-mediated vasoconstriction. This effect is not mediated by stimulation of the NO pathway and is not associated with improvement of the vasodilator responses to NO. This suggests, therefore, that mechanisms different than NO are involved in mediating the vascular benefits of Ang-(1-7) in these patients.
Author Disclosures: F. Schinzari: None. M. Tesauro: None. A. Veneziani: None. N. Mores: None. U. Campia: Speakers Bureau; Modest; BMS/PFIZER. N. Di Daniele: None. C. Cardillo: None.
- © 2016 by American Heart Association, Inc.