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Small Vessel Remodeling and Impaired Endothelial-Dependent Dilatation in Subcutaneous Resistance Arteries from Patients with Acromegaly

Department of Endocrinology (A.N.P., P.J.T.), Christie Hospital, Manchester M20 4BX, United Kingdom; Department of Cardiovascular Medicine (A.S.I., K.C., A.M.H.), Manchester Royal Infirmary, Manchester M13 9NT, United Kingdom; and National Primary Care Research and Development Centre (I.G.), University of Manchester, Manchester M13 9PL, United Kingdom

Address all correspondence and requests for reprints to: A. M. Heagerty, Professor of Medicine, Cardiovascular Research Group, Division of Cardiovascular and Endocrine Sciences, Core Technology Facility (3rd Floor), University of Manchester, 46 Grafton Street, Manchester M13 9NT, United Kingdom. E-mail: tony.heagerty{at}manchester.ac.uk.

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 Ca²⁺-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 hyperpolarizing factor bioavailability, both of which may contribute to the early mortality from cardiovascular disease.