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

Abstract

Context: Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, both of which cause small vessel remodeling and endothelial dysfunction. Objective: To understand the structure and function of small arteries in acromegaly, subcutaneous blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD:56+/-15y, 14m), 23 in remission (CD:55+/-12y, 15m) and 20 healthy controls (55+/-11yrs, 10m) and examined in-vitro using pressure myography. Design: Contractile responses to cumulative noradrenaline concentrations were recorded followed by dose dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (L-NAME) and cyclooxygenase inhibitor (indomethacin). Following perfusion with Ca(2+)-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180mmHg). 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 versus 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 following L-NAME 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 NO and EDHF bioavailability, both of which may contribute to the early mortality from cardiovascular disease.