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(Hypertension. 1996;27:1277-1283.)
© 1996 American Heart Association, Inc.

Articles

Lack of Cross Talk Between ₁-Adrenergic and Angiotensin Type 1 Receptors in Neurons of Spontaneously Hypertensive Rat Brain

Hong Yang; Di Lu; Mohan K. Raizada

From the Department of Physiology, University of Florida, College of Medicine, Gainesville.

Correspondence to Mohan K. Raizada, PhD, College of Medicine, Department of Physiology, PO Box 100274 JHMHC, 1600 SW Archer Rd, Gainesville, FL 32610. E-mail mraizada@phys.med.ufl.edu.

Abstract Norepinephrine causes downregulation of angiotensin II (Ang II) receptors in Wistar-Kyoto rat (WKY) brain neuronal cultures. The aim of this study was to compare the cross talk between Ang II and ₁-adrenergic receptors in these neuronal cultures. Norepinephrine causes a 66% decrease in B_max of Ang II type 1 (AT₁) receptors in neuronal cultures of WKY brain. This decrease is mediated by the interaction of norepinephrine with the _1A-adrenergic receptor subtype. Norepinephrine also causes a decrease in mRNA levels for AT₁ receptors. A maximal decrease of 83% in AT₁ receptor mRNA is observed in 8 hours with 100 µmol/L norepinephrine, is blocked by 5-methyluradipil, and involves inhibition of AT₁ receptor transcription. Furthermore, decreases in the AT₁ receptor and its mRNA are associated with a significant attenuation of AT₁ receptor–mediated stimulation of norepinephrine transporter mRNA in WKY brain neurons. In contrast, norepinephrine does not decrease AT₁ receptors or mRNA and has no effect on Ang II stimulation of norepinephrine transporter mRNA in neuronal cultures of spontaneously hypertensive rat brain. Thus, these data show that norepinephrine-mediated downregulation of AT₁ receptors is associated with a parallel decrease in AT₁ mRNA and Ang II stimulation of norepinephrine transporter mRNA and involves the _1A-adrenergic receptor in neurons of WKY brain. This cross talk between the two receptors is lacking in neurons of spontaneously hypertensive rat brain.

Key Words: receptors, angiotensin II • RNA, messenger • brain • receptors, adrenergic, alpha • angiotensin II • norepinephrine • neurons

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