Small vessel remodeling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly.
AffiliationDepartment of Endocrinology, Christie Hospital, Manchester, UK; Department of Cardiovascular Medicine, Manchester Royal Infirmary, Manchester, UK; National Primary Care Research and Development Centre, University of Manchester, UK.
MetadataShow full item record
AbstractContext: 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.
CitationSmall vessel remodeling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly. 2009: J. Clin. Endocrinol. Metab.
JournalThe Journal of Clinical Endocrinology and Metabolism
- The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin--induced diabetic rats is restored by 5-methyltetrahydrofolate.
- Authors: De Vriese AS, Van de Voorde J, Blom HJ, Vanhoutte PM, Verbeke M, Lameire NH
- Issue date: 2000 Sep
- Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats.
- Authors: Nakazawa T, Kaneko Y, Mori A, Saito M, Sakamoto K, Nakahara T, Ishii K
- Issue date: 2007 Mar
- Mutation of the circadian clock gene Per2 alters vascular endothelial function.
- Authors: Viswambharan H, Carvas JM, Antic V, Marecic A, Jud C, Zaugg CE, Ming XF, Montani JP, Albrecht U, Yang Z
- Issue date: 2007 Apr 24
- Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms.
- Authors: Prisby RD, Wilkerson MK, Sokoya EM, Bryan RM Jr, Wilson E, Delp MD
- Issue date: 2006 Jul
- Role of EDHF in the vasodilatory effect of loop diuretics in guinea-pig mesenteric resistance arteries.
- Authors: Pourageaud F, Bappel-Gozalbes C, Marthan R, Freslon JL
- Issue date: 2000 Nov