Effects of endothelin receptor type A antagonism and nitric oxide synthase inhibition on cerebral blood flow in hypertensive rats.
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 micrograms 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.
Granstam
S O
SO
Department of Internal Medicine, University of Uppsala, Sweden.
Granstam
E
E
Fellström
B
B
Lind
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)