Small vessel remodeling and impaired endothelial- dependent dilatation in subcutaneous resistance arteries from patients with acromegaly

Context: Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, and both cause small vessel remodeling and endothelial dysfunction. Objective: To understand the structure and function of small arteries in acromegaly, sc blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD; age, 56 ± 15 yr; 14 males), 23 patients in remission (CD; age, 55 ± 12 yr; 15 males), and 20 healthy controls (age, 55 ± 11 yr; 10 males) and examined in vitro using pressure myography. Design: Contractile responses to cumulative noradrenaline concentrations were recorded and followed by dose-dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and cyclooxygenase inhibitor (indomethacin). After perfusion with Ca 2+-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180 mm Hg). Results: Wall thickness and wall:lumen ratio were increased in AD, reduced with treatment but remained greater in CD than controls. Wall cross-sectional area was increased in AD vs. controls (P <0.001), decreased with treatment (AD vs. CD, P <0.001), but remained higher than controls (CD vs. controls, P = 0.015). Growth index was increased in AD (20%) compared to controls (CD, 9%). Contractility was similar in all groups. Endothelial-dependent dysfunction was evident in AD compared with CD (P <0.001) and controls (P <0.01). Dilation did not change after N-nitro-L-arginine methyl ester but was impaired after indomethacin incubation. Conclusion: Active acromegaly is associated with hypertrophic remodeling of the vascular wall and embarrassed endothelial function due to reduced nitric oxide and endothelium-derived hyper- polarizing factor bioavailability, both of which may contribute to the early mortality from cardiovascular disease. Copyright © 2009 by The Endocrine Society.