Aim: 

Glitazones are beneficial for the treatment of the symptoms of metabolic syndrome, such as insulin resistance, hypertension or microangiopathy. Interested in the actions of glitazones on microangiopathy, we have studied the effects of pioglitazone and rosiglitazone (both, 10^-5 M), on microvessels, specifically on: a) endothelial function and, b) smooth muscle calcium mobilization.

Methods: 

Microvessels were obtained from the mesenteric bed (3^rd branch) of: 1) spontaneously hypertensive rats (SHR), 2) normotensive Wistar Kyoto rats (WKY) and, 3) metabolic syndrome rats (SHR-OB).

Results: 

a) Endothelial function, assessed by acetylcholine curves, showed a marked impairment in microvessels from SHR compared to WKY, which was even worse in SHR-OB. Both glitazones (or indomethacin) restored acetylcholine-induced relaxations in SHR microvessels back to a WKY-like shape. In SHR-OB, relaxations were improved by glitazones only partially, but totally when incubated together with indomethacin. Acetylcholine relaxations were abolished by inhibition of NO synthase in SHR microvessels, but were unchanged in SHR-OB. Glitazones partially recovered those impaired relaxations. b) Smooth muscle calcium mobilization, assessed by calcium imaging in whole microvessels, revealed that pioglitazone and specially, rosiglitazone, diminished the rise in intracellular calcium concentration caused by KCl (75 mM) in SHR and even more markedly, in SHR-OB microvessels.

Conclusion: 

Glitazones improve microvascular endothelial function and lower calcium mobilization in smooth muscle cells in hypertension and metabolic syndrome in a distinctive manner. In both cases, the SHR and SHR-OB increase in endothelial function involves the cyclooxygenase pathway. Glitazones significantly improve the severe endothelial disfunction caused by the NO pathway inhibition of the SHR.