Enhancement of vascular endothelial function by recombinant human thyrotropin.
BACKGROUND
The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors.


OBJECTIVE
The study was designed to determine whether TSH exerts any effect on vascular homeostasis.


METHODS
Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography.


RESULTS
Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion.


CONCLUSIONS
rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.
Napoli
Raffaele
R
Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Via Pansini 5, Naples, Italy. napoli@unina.it
Biondi
Bernadette
B
Guardasole
Vincenzo
V
D'Anna
Carolina
C
De Sena
Antonietta
A
Pirozzi
Concetta
C
Terracciano
Daniela
D
Mazzarella
Claudia
C
Matarazzo
Margherita
M
Saccà
Luigi
L
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology*
D011994:Recombinant Proteins; D013972:Thyrotropin