Abstract 138: Angiotensin Converting Enzyme (ACE) Inhibition Reverses Vasoconstriction and Impaired Dilation of Pial Collaterals During Chronic Hypertension

Abstract

Introduction: Leptomeningeal anastomoses (LMAs) are pial collaterals that perfuse the penumbra and are important for stroke outcome. In the current study, we investigated mechanisms by which hypertension causes LMA vasoconstriction that is known to limit the amount of salvageable tissue when stroke occurs during chronic hypertension. We hypothesized that increased vasoreactivity of LMAs from hypertensive rats is angiotensin II (Ang II)-dependent. Methods: Spontaneously hypertensive rats (SHRs, n=8/group) were treated with the ACE inhibitor captopril, hydralazine to lower blood pressure (BP) independent of AngII, or vehicle for 5 weeks in drinking water. A group of normotensive Wistar rats (n=8) had regular drinking water served as controls. BP was measured twice weekly by tail cuff. LMAs were isolated and studied in pressurized conditions. Vasoactivity of LMAs, including myogenic responses, reactivity to the Rho-kinase inhibitor Y-27632 and nitric oxide (NO) were measured. Results: Both captopril and hydralazine lowered BP in SHRs similar to Wistar rats. LMAs from untreated SHRs had increased myogenic tone vs. Wistar that was normalized by captopril but not hydralazine (Fig. 1A). LMAs from all groups constricted similarly to NO synthase inhibition; however, the vasodilatory response of LMAs to the NO donor sodium nitroprusside, was impaired in SHRs vs. Wistar rats that was restored by captopril and not hydralazine (Fig. 1B). Maximum vasodilatory response of LMAs to Y-27632 was impaired in SHRs compared to Wistar rats (28±3% vs. 81±4%, p<0.01) that was restored by captopril (84±5%) and partially by hydralazine (59±4%) treatment. Conclusions: ACE inhibition during chronic hypertension reversed vascular dysfunction and hyperconstriction of LMAs, an effect that could improve stroke outcome by increasing collateral perfusion. In addition, lowering BP alone without inhibition of Ang II, may not provide the same protective effect on pial collaterals.