Effect of postischemic hypoperfusion on vasodilatory mechanisms in cats.

We addressed the mechanism for reduced pial vascular reactivity to muscarinic stimulation by evaluating pial vessel responses to receptor-dependent [10(-5) M acetylcholine (ACh)] and independent (10(-5) M A-23187) agonists and the endothelium-independent nitric oxide (NO) donor [10(-5) M nitroprusside (NP)]. Cerebral blood flow (CBF, microspheres) and pial arteriolar diameters (intravital microscopy) were measured in halothane-anesthetized cats. Cats (n = 13) were treated with 12 min of near-complete global cerebral ischemia, whereas control animals (n = 9) were identically instrumented but were not submitted to ischemia. Postischemic hypoperfusion was evident in most animals at 60 min of reperfusion, accompanied by attenuated pial arterial dilation to topical ACh (baseline dilation 23 +/- 4% vs. postischemia 11 +/- 3%) and A-23187 (16 +/- 4 vs. 0 +/- 3% dilation). Dilation to NP was unaffected. CBF response to intravenous administration of the muscarinic receptor agonist oxotremorine was also decreased throughout the forebrain (162 +/- 12 vs. 116 +/- 6% increase in flow) in these cats. These data suggest that endothelium-dependent vasodilation with topical muscarinic agonists is impaired during hypoperfusion, but vascular smooth muscle responsivity to NO remains intact. We conclude that the defect in the signal transduction pathway is not limited to the receptor and may involve an abnormality with NO synthesis or its destruction within endothelium.