Effects of endothelin receptor type A antagonism and nitric oxide synthase inhibition on cerebral blood flow in hypertensive rats

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Abstract
Effects of the endothelin receptor type A antagonist BQ 123 and the NO synthase inhibitor L‐NMMA on cerebral blood flow were studied in vivo in anaesthetized hypertensive (SHR) and normotensive (WKY) rats. The effects of acetylcholine following pre‐treatment with these drugs were also studied with the microsphere method for blood flow determination in the cortex, thalamus, caudatus, pons, medulla, cerebellum and hypophysis. BQ 123 (1 mg kg−1) induced only minor effects on cerebral blood flow in both strains (n = 8), whereas L‐NMMA (N = 8; 20 mg kg−1) reduced regional cerebral blood flow significantly in most regions (21–54%) in the hypertensive, but not in the normotensive rat. In normotensive rats pre‐treated with BQ 123 intravenous administration of acetylcholine (2 μg kg−1 min−1) induced a widespread significant increase (20–50%) in cerebral blood flow despite a reduction of the mean arterial blood pressure, while no significant effects were seen in hypertensive animals. Intravenous infusion of acetylcholine in animals pre‐treated with L‐NMMA did not affect cerebral blood flow in most regions in either of the two rat strains. In conclusion, a vasodilatory response to acetylcholine was found following endothelin receptor A antagonism in the WKY rat only, suggesting a role for endothelin in the control of cerebral blood flow in this strain. Furthermore, a higher basal vasodilating nitric oxide‐tone seems to be present in the hypertensive rat compared with the normotensive rat.