Effects of a PPAR-gamma receptor agonist and an angiotensin receptor antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or hypertensive rats.

Abstract

SummaryAimThe aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats.MethodsMale Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose–response curves to phenylephrine (Phe) (10-9–10-5 M) and clonidine (Clo) (10-9–10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 μM) and/or losartan (10 μM).ResultsPioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups.ConclusionThe sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension.