P-559: Role of bradykinin (BK) in the cardiovascular and metabolic effects of omapatrilat (OMA) in SHR

Abstract

We have shown in previous works that the vasopeptidase inhibitor, Oma is able to reduce blood pressure (BP) and to improve the insulin sensitivity index (ISI) of SHR. The aim of this study was to evaluate the participation of BK in these effects. Adult male SHR were treated for 12 consecutive weeks with Oma 100μg/kg/day by gavage (SHR+Oma, n=22). Untreated SHR were used as controls (SHR, n=18). At the end of the follow-up, rats from both groups (SHR, n=10 and SHR+Oma, n=17) underwent to an euglicemic hyperinsulinemic clamp to determine the glucose uptake (GU) and ISI. In 7 rats of the SHR+Oma group the insulin clamp was performed during an acute BK-B2 receptor blockade with HOE-140 (33μg/kg/SC + continuous infusion of 330ng/min/2hours). In a separate set of experiments, BP of 8 SHR and 5 SHR+Oma were monitored for 60 minutes before and during HOE-140 infusion.

Results * p<0.05 vs SHR; #p< 0.05 vs SHR+Oma (See Table)

	SHR	SHR+OMA	SHR+OMA+HOE
BP(mmHg)	156.3 ± 9.2	124.0 ± 8.9*	125.0 ± 12.7*
GU (mg/min)	11.7 ± 6.5	18.7 ± 8.4*	13.7 ± 6.6#
ISI	15.9 ± 5.7	25.8 ± 6.9*	17.8 ± 4.7#

Conclusion: Bradykinin preservation is responsible for the improvement on glucose metabolism, but not for the BP reduction induced by omapatrilat, a vasopeptidase inhibitor.

omapatrilat, bradykinin, insulin resistance