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 inhibitorL-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), whereasL-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 g 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 withL-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.

Keywords: acetylcholine; cerebral blood flow; endothelin receptor antagonist; hypertension; microsphere method; nitric oxide; nitric oxide synthase inhibition; rats inbred SHR

Document Type: Original Article

DOI: http://dx.doi.org/10.1046/j.1365-201X.1998.00419.x

Affiliations: 1: Department of Internal Medicine, University of Uppsala, Sweden 2: Department of Ophthalmology, University of Uppsala, Sweden

Publication date: October 1, 1998

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