Abstract 223: Leptomeningeal Arteriole Vasoconstriction during Hypertension: Targeting Pial Collaterals in Stroke Treatment

Abstract

Introduction: Collateral perfusion via leptomeningeal arterioles (LMAs) between middle and anterior cerebral artery (MCA/ACA) territories sustains the penumbra during MCA occlusion (MCAO) and is a key variable in stroke outcome. Hypertension is associated with poor stroke outcome, little penumbral tissue and larger infarctions. Here, we investigated the vasoactive properties of isolated and pressurized LMAs from normotensive and hypertensive animals as a contributor to poor collateral flow. Hypothesis: Compared to normotensive animals, LMAs from hypertensive animals are vasoconstricted that limits collateral perfusion and penumbral tissue. Methods: LMAs between MCA and ACA distal branches were dissected from 18 wk old male normotensive Wistar Kyoto (WKY, n=14) and spontaneously hypertensive rats (SHR; n=16), mounted on glass cannulas and studied pressurized. Results: LMAs from WKY had little basal tone and responded passively to increased pressure from 5 to 80 mmHg. In contrast, LMAs from SHR had considerable tone and responded to pressure with vasoconstriction (Figure 1). Dilatory responses were also diminished in LMAs from SHR vs. WKY, including to the voltage operated calcium channel inhibitor diltiazem (63±6% vs. 88±2% at 10 -5 M; p<0.01), the NO donor sodium nitroprusside (23±6% vs. 74±6% at 10 -5 M; p<0.01), and to 15mM KCl that activates inward rectifier K + channels (-5±45% vs. 78±10%; p<0.01). Structurally, passive diameters of LMAs from SHR were smaller but not significantly different from WKY, suggesting therapeutic opening of collaterals may be possible. Conclusions: The relatively passive nature of LMAs from WKY would be conducive to retrograde flow during MCAO whereas the vasoconstrictive response of LMAs from SHR could limit collateral perfusion. Therapies that alleviate LMA vasoconstriction may help sustain penumbral flow and extend the time for treatment in those patients that have poor collaterals.