This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Paisley, A. N. Articles by Heagerty, A. M. Search for Related Content PubMed PubMed Citation Articles by Paisley, A. N. Articles by Heagerty, A. M. Related Collections Neuroendocrinology and Pituitary

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.