Hypertrophic Remodeling of Subcutaneous Small Resistance Arteries in Patients with Cushing's Syndrome

Damiano Rizzoni*, Enzo Porteri, Carolina De Ciuceis, Luigi F. Rodella, Silvia Paiardi, Nicola Rizzardi, Caterina Platto, Gianluca E. M. Boari, Annamaria Pilu, Guido A. M. Tiberio, Stefano M. Giulini, Gaia Favero, Rita Rezzani, Claudia Agabiti Rosei, Giuseppe Bulgari, Daniele Avanzi,  and Enrico Agabiti Rosei

Clinica Medica (D.R., E.P., C.D.C., S.P., N.R., C.P., G.E.M.B., A.P., C.A.R., G.B., D.A., E.A.R.), and Clinica Chirurgica (G.A.M.T., S.M.G.), Department of Medical and Surgical Sciences; and Chair of Human Anatomy (L.F.R., G.F., R.R.), Department of Biomedical Sciences and Biotechnology, University of Brescia, 25100 Brescia, Italy

* To whom correspondence should be addressed. E-mail: rizzoni@med.unibs.it.

Objective: Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome.

Subjects: We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress.

Results: Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels.

Conclusion: Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1588v1