Endocrine Abstracts (2007) 13 P250

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

Angela Paisley1, Ashley Izzard2, Tony Heagerty2, Kennedy Cruickshank2 & Peter Trainer1

1Christie Hospital, Manchester, United Kingdom; 2Manchester Royal Infirmary, Manchester, United Kingdom.

Patients with acromegaly die prematurely from CVD. Hypertension is more prevalent with increased peripheral vascular resistance thought to be due to structural remodelling of resistance vessels.

We investigated structural properties and reactivity of small arteries in 20 healthy controls(55±11 years, 10 m) and 43 patients with acromegaly (55±14 years, 29 m), split into active disease (AD, n=17, 56±15 years, 13 m) or remission (CD, n=26, 54±13 years, 16 m). Patients and controls were matched for age, total and LDL cholesterol, and BP; BMI differed between groups (P=0.01).

Small resistance arteries were dissected from biopsies of gluteal subcutaneous fat, and studied using a pressure arteriograph system. Contractile responses to increasing noradrenaline concentrations were recorded followed by dilator responses to cumulative acetylcholine (ACh) concentrations. The ACh protocol was repeated after incubation with a nitric oxide synthase inhibitor (L-NAME) and cyclooxygenase inhibitor (indomethacin). To determine structure, following perfusion with Ca2+-free physiological saline solution, wall thickness and lumen diameter were recorded at varying intraluminal pressures(3–180 mmHg).

Wall thickness was increased in patients with AD (P=0.01) and CD (P=0.049) compared with controls, and wall/lumen ratio (AD:P=0.019, CD:P=0.026). Wall cross-sectional area did not differ significantly but growth index was increased in AD (23%) versus CD (6%) and remodelling index increased in CD (88%) versus AD (5%). The stress-strain relationship was shifted to the left in all patients suggesting reduced distensibility.

Contractility did not differ between groups. Dilatation to ACh was impaired in AD compared with CD (P=0.021) suggesting endothelial-dependent dysfunction (EDD). Dilation did not change following L-NAME but was impaired after indomethacin incubation.

In summary, structural changes in the vasculature are dependent upon disease activity in patients with acromegaly. Reduced distensibility is demonstrated, plus hypertrophic changes in AD and remodelling in CD. EDD is also present due to altered NO and EDHF bioavailability with most dilation due to the prostaglandin component. Vascular wall hypertrophy is prognostically adverse in hypertension and diabetes; suggesting this is an unfavourable finding in acromegaly.

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