1026 EARLY BRIEF TREATMENT WITH ANGIOTENSIN CONVERTING ENZYME INHIBITOR, PERINDOPRIL, PREVENTS AORTIC CALCIFICATION IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Background: Aortic calcification is a potent risk marker of cardiovascular events. Aortic calcification contributes to arterial stiffness and increased pulse pressure. Early angiotensin converting enzyme inhibition (ACEi) in spontaneously hypertensive rats (SHR) during a critical treatment window prevents aortic stiffness in adulthood. However, the effect of ACEi on aortic calcification is unknown. Method: ACEi (perindopril, 3 mg/kg/day, by gavage) was delivered during the pre- (6-10 weeks, SHR(Tx)y, n = 6) and established (20-24 weeks of age, SHR(Tx)o, n = ?) hypertensive phases. Vascular stiffness of the thoracic and abdominal aortic segments at their corresponding anaesthetised mean aortic pressure (MAP) was calculated from beat-to-beat pulse wave velocity (PWV) measurements in-vivo, using two 1.4F pressure catheters introduced to the thoracic and abdominal aorta, positioned a known distance apart. Aortas were harvested post-mortem and divided into thoracic and abdominal segments at the renal bifurcation for quantification of calcium content using atomic absorption spectrophotometry. Results were compared to untreated SHR, and the normotensive control strain, Wistar-Kyoto (WKY). Results: Perindopril significantly decreased MAP (-43%, P=0.0005), isobaric thoracic PWV (-19%, P=0.002) but not abdominal PWV. Thoracic aorta of the SHR(Tx)y group calcified 54% less than that of SHR controls (p=0.001), and approximated values of the normotensive control strain, with no difference detected in the abdominal aorta (p=0.09). The SHR(Tx)o group did not differ from SHR controls in any measured parameters. Conclusion: This study shows direct evidence of the persistent effect of early, but not late, ACEi in prevention of arterial stiffness associated with hypertension and corresponding aortic calcification.