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

• Published in: The journal of clinical endocrinology and metabolism 2009-04, Vol.94 (4), p.1111-1117
• Main Authors: Paisley, Angela N., Izzard, Ashley S., Gemmell, Islay, Cruickshank, Kennedy, Trainer, Peter J., Heagerty, Anthony M.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Acromegaly - physiopathology; Adipose Tissue - blood supply; Adult; Aged; Arterioles - physiology; Arterioles - physiopathology; Biological and medical sciences; Cyclooxygenase Inhibitors - pharmacology; Endocrinopathies; Endothelium, Vascular - physiopathology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Indomethacin - pharmacology; Male; Medical sciences; Middle Aged; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Reference Values; Skin - blood supply; Vasodilation - drug effects; Vasodilation - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-0948

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. Active acromegaly is associated with hypertrophic remodeling of the vascular wall and endothelial dysfunction.