Effects of pioglitazone and rosiglitazone on aortic vascular function in rat genetic hypertension

Silvia Llorens, Yolanda Mendizabal, Eduardo Nava
European Journal of Pharmacology 2007 December 1, 575 (1): 105-12
Glitazones have beneficial antihypertensive effects independent of their insulin-sensitizing action. We have studied the effects of pioglitazone and rosiglitazone on the endothelial ability to counteract vascular smooth muscle contractility in genetic hypertension. To achieve this, we measured isometric responses of aortic segments obtained from spontaneously hypertensive rats. The effects of glitazones on endothelial function were studied by assessing the endothelial modulation of phenylephrine-induced isometric contractions (10(-9)-10(-5) M) in the presence or absence of pioglitazone or rosiglitazone (10(-5) M), added directly to an organ bath or orally administered to the rats (pioglitazone, 10 mg/kg). The role of both NO and prostanoids was analyzed by performing experiments in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and/or indomethacin (both 10(-5) M) in the organ bath. Concentration-dependent contractions to L-NAME (10(-6)-3 x 10(-4) M) in the presence or absence of glitazones were carried out as an estimation of basal NO release. Pioglitazone, but not rosiglitazone, increased contractile responses to phenylephrine in intact vessels. The contractile responses to phenylephrine obtained in the presence of glitazones were markedly diminished by indomethacin, but enhanced by L-NAME. Analogous results were obtained in aortas from pioglitazone-chronically treated animals. L-NAME concentration-dependent contractions were enhanced by both glitazones. Both glitazones lowered the sensitivity to acetylcholine (10(-9)-10(-5) M). In conclusion, pioglitazone and rosiglitazone alter vascular function differentially and through endothelium-dependent mechanisms. These drugs act over the same pathways on the endothelium where they have a dual action, increasing both production of vasoconstrictor prostanoids and NO. The balance between both vasoactive substances determines the vascular response to glitazones.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"