Abstract 127: Pharmacological Regression of Pulse Pressure Prevents Further Cerebrovascular Dilatation in Rats with Elastase-Induced Intracranial Aneurysm
Objective: Highly pulsatile blood pressure (BP) transmits into small vessels in the brain, potentially damages cerebrovasculature, causing transient ischaemic attack or stroke. We examined the effects of pulse pressure (PP) regression using an angiotensin converting enzyme inhibitor (perindopril, ACEI) or a thiazide diuretic (hydrochlorothiazide, HCTZ) on the incidence of intracranial aneurysms.
Materials and methods: 12 weeks old pre-hypertensive Spontaneously Hypertensive Rat (SHR) received ACEI (3mg/kg/day) or HCTZ 20mg/kg/day in drinking water a week before aneurysm induction. Aneurysms were induced with a single stereotaxic microinjection of elastase (30milli-units) into the right basal cistern using a fine glass pipette (tip size <0.05mm) through a burr hole at 0.9mm posterior, 1.4mm lateral to the bregma, and 3.3mm deep. Control SHR received inactivated elastase heated to 1000C and were untreated. Rats were recovered with ACEI or HCTZ continued for 8 weeks. Rats were then anaesthetised (urethane1.3 g/kg, i.p.), their BP measured at common carotid artery before euthanised and fixed with a bromophenol blue dye and gelatin mixture for examination of the cerebrovasculature. Incidence was counted positive when the rat showed at least one localised outward bulging of the vascular wall with diameter >50% of the basilar artery diameter.
Results: 13/30 rats developed intracranial aneurysms 8 weeks post injection. Table shows both ACEI and HCTZ reduced the incidence of intracranial aneurysms with ACEI more efficacious compared with HCTZ. Both ACEI and HCTZ effectively reduced MAP, SBP, and DBP in SHR. However, only ACEI significantly reduced PP.
Conclusion: ACEI was more efficacious in preventing further dilatation of elastase-induced intracranial aneurysms. This effect was associated with marked regression of PP. This study suggests that pharmacological interventions to delay aneurysm growth should target at regressing PP rather than MAP per se.
Author Disclosures: K. Ng: None. J. Li: None. V. Gupta: None. Y. Qian: None.
- © 2014 by American Heart Association, Inc.