ANGIOTENSIN-II AND ATRIAL-NATRIURETIC-FACTOR RECEPTOR INTERACTIONS AT THE BLOOD-BRAIN-BARRIER

Data from several laboratories indicate that cerebral endothelial cells possess cell surface receptors for numerous vasoactive agents including angiotensin II (AII) and atrial natriuretic factor (ANF). The intracellular messengers of these receptors as well as possible receptor interactions were explored. ANF increased cGMP 10-fold over basal levels while incubation of the microvessels with All did not significantly affect the level of this nucleotide. In contrast, AII significantly potentiated the increase in cGMP by ANF Incubation of cerebral microvessels with AII resulted in a significant increase in the intracellular mediator of PI hydrolysis, 1,2-diacylglycerol (DG). ANF had no affect on DG or on the AII mediated increase of DG. Finally, data at the level of receptor binding indicated that while ANF decreased [H-3]angiotensin binding to cerebral microvessels, AII had no effect on the binding of ANF to its receptor. The results of the present study demonstrate that AII can potentiate the regulation of cGMP by ANF and suggest the possibility of receptor interactions in control of blood-brain barrier function.