Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function

Abstract

We investigated the effects of circulating factors in serum obtained from patients in the acute phase of different subtypes of ischemic stroke on non-ischemic cerebral and mesenteric arteries, as a potential mechanism involved in influencing regional perfusion and thus clinical evolution. Posterior cerebral arteries (PCAs) and mesentery arteries (MAs) isolated from Wistar Kyoto rats were perfused with serum from acute stroke patients with large vessel disease without (LVD) or with hypertension (LVD + HTN), cardioembolism with hypertension (CE + HTN), or physiologic saline as controls. Myogenic activity and nitric oxide-dependent vasorelaxation were assessed after 2 h of intraluminal exposure to serum. Vascular function was differentially affected by sera. Exposure to LVD serum increased myogenic tone and produced endothelial dysfunction in both PCAs and MAs. However, CE + HTN serum increased tone and decreased smooth muscle sensitivity to NO in vessels from both vascular beds. LVD + HTN serum was associated with reduced smooth muscle sensitivity to NO in vessels from both vascular beds but increased tone only in PCAs. Inflammation and oxidative stress, determined by measurement of high sensitivity C-reactive protein, uric acid, and free 8-isoprostane, were enhanced in all the serum groups. These results demonstrate vasoactive properties of acute stroke serum related to stroke subtypes that could potentially contribute to the pathogenesis of early hemodynamic-based clinical events.

Keywords: Acute stroke; Circulating factors; Free 8-isoprostane; Inflammation; Oxidative stress; Stroke subtypes.

Figure 1

Effect of acute stroke serum on myogenic reactivity in non-ischemic cerebral and mesenteric vessels. A: Active diameter changes in response to stepwise increase of intravascular pressure in PCAs. PCAs perfused with CE+HTN serum had significantly smaller diameters than control at the higher pressures. B: Active diameter changes in response to stepwise increase of intravascular pressure in MAs. MAs perfused with LVD+HTN serum were characterized by low myogenic reactivity. MAs perfused with LVD and CE+HTN serum had significantly smaller diameters that did not change with increased pressure. *p<0.05 vs. Control; #p<0.05 vs. LVD+HTN serum

Figure 2

Effect of acute stroke serum on myogenic tone in non-ischemic cerebral and mesenteric vessels at 75 mm Hg. Exposure to LVD and CE+HTN serum produced increased tone in PCAs and MAs, exposure to LVD+HTN serum only in PCAs. *p<0.05 vs. Control; #p<0.05 vs. LVD+HTN serum; ^p<0.01 vs. PCAs perfused with the same serum

Figure 3

Effect of acute stroke serum on percent constriction to L-NAME (10⁻³ M) in PCAs and MAs. Serum from all groups of stroke patients reduced constriction to L-NAME in PCAs compared to control, while no differences were measured among MA groups. *p<0.05 vs. Control; ^p<0.01 vs. PCAs perfused with the same serum

Figure 4

Effect of acute stroke serum on NO-dependent vasodilation. (A, B) show percent reactivity in PCAs receiving increasing concentrations (10⁻⁸ M to 10⁻⁵ M) of acetylcholine and SNP, respectively. The presence of LVD serum significantly reduced reactivity to acetylcholine while did not affect reactivity to SNP. The presence of CE+HTN serum caused reduced reactivity to SNP. (C, D) show the same experimental conditions in MAs as A and B. The presence of serum from all the groups of patients reduced reactivity to acetylcholine at 10⁻⁸ and 3×10⁻⁸ M. The presence of LVD+HTN significantly reduced reactivity to SNP. *p<0.05 vs. Control; #p<0.05 vs. LVD+HTN serum; †p<0.05 vs. LVD serum