Vascular reactivity in acromegalic patients: preliminary evidence for regional endothelial dysfunction and increased sympathetic vasoconstriction.
OBJECTIVE
Hypertension is found in one-third of acromegalic patients. An heterogenous distribution of cardiac output has been recently demonstrated in acromegalic patients with an increased blood flow at the level of the upper limb, suggesting that acromegalic patients may have some degree of endothelial dysfunction. Elsewhere, studies involving hypopituitary GH-deficient adults have shown that GH and/or IGF-I may have direct effect on endothelial function.


METHODS
We thus compared cutaneous vasoreactivity responses in 10 normotensive patients with active acromegaly (A) (six women and four men) aged 25-59 (mean, 43.2 years), whose basal GH and IGF-I levels ranged from 7.4 to 158 mU/l and from 401 to 1690 microg/l, respectively, and in 10 normal age- and sex-matched controls (NC) by means of Laser Doppler flowmetry at the levels of the palm and the dorsum of the right hand. Circulatory skin velocities were studied basally and after increasing skin temperature to 44 degrees C (in order to study direct nonspecific vasodilatation response which is independent of endothelial or autonomous nervous system and reflects normal vascular muscle function), after shear-stress (known to produce flow-dependent vasodilatation, mediated by nitric oxyde (NO) originating from endothelial cells) and after cold-stress applied on the opposite hand (known to produce vaso-constriction mediated by the sympathetic nervous system).


RESULTS
The warm test induced a significant (P<0.001) and similar increase in both dorsal and palmar skin perfusion in A (mean +/- SD) (240+/-96 and 238+/-134%, respectively) and NC (232+/-137 and 233+/-73, respectively). Ischaemia release induced a significant increase in both dorsal and palmar skin blood flows in the two groups (P<0.001), but reactivities in acromegalic patients were about one half of those measured in controls (22.9+/-16.2% (A) vs. 46.9 25% (NC), 2P<0.02, at the level of the dorsum; and 45.0+/-43.6% (A) vs. 104.7+/-40.1 (NC), 2P<0.01, at the level of the palm). Cold pressor test resulted in significant decreases in both cutaneous flows (P<0.01) in the two groups, with a larger vasoconstriction (that did not reach statistical significance) in acromegalic patients as compared with controls (P< 0.10).


CONCLUSIONS
Vascular smooth cell ability to produce skin vasodilatation is normal but endothelium-dependent vasodilatation appears to be impaired while sympathetic-mediated vasoconstrictive response might be increased in acromegaly. This endothelial dysfunction may contribute to hypertension and represent a risk factor for cardiovascular complications in acromegaly.
Maison
P
P
Service de Pharmacologie Clinique and Institut Fédératif de Recherches, Centre Hospitalier Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris and Faculté de Médecine Paris-Sud, Kremlin-Bicêtre, France.
Démolis
P
P
Young
J
J
Schaison
G
G
Giudicelli
J F
JF
Chanson
P
P
D000172:Acromegaly / Q000097:blood / Q000503:physiopathology*; D000328:Adult; D016022:Case-Control Studies; D003080:Cold Temperature; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006225:Hand; D006358:Hot Temperature; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014661:Vasoconstriction
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone