Hypertensive patients (HTs) have impaired nitric oxide (NO) activity, but the mechanism underlying this abnormality is unknown. We have recently observed an increased endothelin (ET) vasoconstrictor tone in HTs related to increased production of the peptide. In the present study, we investigated whether the increased ET activity of HTs could contribute to their impaired NO-dependent vasodilator function. To this end, the vasodilator responses to acetylcholine (ACh; 7.5, 15, and 30 ug/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP; 0.8,1.6, and 3.2 ug/min), an exogenous NO donor, were assessed before and after nonselective blockade of ETA and ETB receptors by combined infusion of BQ-123 (ETA blocker; 100 nmol/min) and BQ-788 (ETB blocker; 50 nmol/min for 60 min) in 6 HTs. Drugs were infused into the brachial artery and forearm blood flow (FBF) was measured by strain-gauge plethysmography. The increases in FBF from baseline induced by the 3 doses of ACh were significantly potentiated by nonselective blockade of ET receptors (0.47+/-0.21(mean+/-SEM), 2.73+/-2.08, and 4.71+/-2.48 mL/min/dL before vs 3.38+/-1.41, 6.06+/-2.56, and 8.67+/-3.06 mL/min/dL after ET antagonism; P=0.01). In contrast, ET receptor blockade did not significantly modify vascular responsiveness to the 3 doses of SNP (2.85+/-0.95, 4.76+/-1.47, and 7.18+/-2.27 mL/min/dL before vs 3.28+/-1.01, 4.94+/-1.48, and 6.5+/-1.84 mL/min/dL after ET antagonism (P=0.97). These findings indicate that endothelial vasodilator function in HTs improves after blockade of ET receptors, suggesting that an increased ET activity may be involved in the pathophysiology of their endothelial dysfunction.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Intramural Research (Z01)
Project #
Application #
Study Section
Cell Biology Integrated Review Group (CB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
United States
Zip Code
Ingram, Jennifer L; Slade, David; Church, Tony D et al. (2016) Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma. Am J Respir Cell Mol Biol 54:41-50
Lugogo, Njira L; Hollingsworth, John W; Howell, Druhan L et al. (2012) Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. Am J Respir Crit Care Med 186:404-11
Ingram, Jennifer L; Huggins, Molly J; Church, Tony D et al. (2011) Airway fibroblasts in asthma manifest an invasive phenotype. Am J Respir Crit Care Med 183:1625-32