Early angiotensin converting enzyme (ACE) inhibition in spontaneously hypertensive rats (SHR) during a critical treatment window prevents the development of hypertension in adulthood. However the effects of such brief ACE inhibition on the structure and function of the aorta is still unknown. This study investigates the effects of ACE inhibition (perindopril, 3mg/kg/day, by gavage) in SHR (n=6) treated at pre- (6-10 weeks) and established (20-24 weeks of age) hypertensive phases. Hemodynamic parameters were recorded in anaesthetised rats over a wide range of blood pressure (BP) induced by infusion of phenylepherine and sodium nitroprusside 1 week after withdrawal of treatment. Vascular stiffness of the thoracic and abdominal aortic segments was calculated from beat-to-beat pulse wave velocity (PWV) measurements in vivo, by using 1.4F pressure catheters inserted in the carotid and femoral arteries and positioned at a known distance apart. Histological and morphological parameters of the segmental aortic media were measured. Heart rate remained steady in all treatment groups. Perindopril significantly decreased systolic BP measured using a tail-cuff method (-32%, P‹0.0001), anaesthetic mean arterial BP (-43%, P=0.0005), proximal (-31%, P=0.0009), distal pulse pressure (-27%, P=0.005), isobaric thoracic PWV (-19%, P=0.002) but not abdominal PWV. All effects in BP and PWV were non-significant in SHR treated late. Morphometric assessment of vascular structure showed that rats, when treated early, significantly decreases medial cross sectional area (-40%, P=0.0002) and wall thickness (-24%, P=0.001) of the abdominal aorta but not in the thoracic segment. ACE inhibition did not reduce the stiffness of the abdominal aorta despite concomitant decrease in both BP and vascular hypertrophy by markedly altering wall structure and content. This study shows that hypotrophy is not significant in the thoracic segment but stiffness was markedly reduced by ACE inhibition. This differential effect suggests the mechanism responsible for this change varies in different parts of the aorta. Effects of ACE inhibition on BP and arterial wall stiffness and structure were non-existent when given later in life.
|Number of pages||1|
|Publication status||Published - 2011|
|Event||Annual Scientific Meeting of the High Blood Pressure Research Council of Australia (32nd : 2010) - Melbourne|
Duration: 1 Dec 2010 → 3 Dec 2010