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(Hypertension. 1995;25:1224-1231.)
© 1995 American Heart Association, Inc.

Articles

-Adrenoceptor Modulation of Norepinephrine and ATP Release in Isolated Kidneys of Spontaneously Hypertensive Rats

Christine Bohmann; Lars Christian Rump; Ulrike Schaible; Ivar von Kügelgen

From Medizinische Universitätsklinik Freiburg, Innere Medizin IV, and Pharmakologisches Institut (I.v.K.), Freiburg im Breisgau, Germany.

Abstract The present study investigates sympathetic cotransmission and its -adrenoceptor–mediated modulation in kidneys of spontaneously hypertensive rats (SHR, 12 to 14 weeks) and age-matched normotensive Wistar-Kyoto rats (WKY). In the presence of cocaine and corticosterone, renal nerve stimulation at 1 Hz (30 seconds) induced a greater outflow of norepinephrine in SHR (4.2±0.2 pmol/g kidney) than in WKY (3.0±0.2 pmol/g kidney). The ₂-adrenoceptor antagonist rauwolscine (0.01 to 1 µmol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in SHR than in WKY. In contrast, the ₁-adrenoceptor antagonist prazosin (0.03 to 3 µmol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in WKY than in SHR. This difference was not observed in the presence of the P₁-purinoceptor antagonist 8-(p-sulfophenyl)theophylline (100 µmol/L). Stimulation at 4 Hz (30 seconds) induced an outflow of ATP (SHR, 12.7±3.3 pmol/g kidney; WKY, 16.7±2.1 pmol/g kidney; perfusion solution without cocaine and corticosterone). Prazosin (0.03 µmol/L) markedly reduced pressor responses to stimulation and inhibited the induced ATP outflow by 60% to 70%. When prazosin (0.03 µmol/L) was present, rauwolscine (0.1 µmol/L) increased the induced outflow of norepinephrine and ATP and markedly enhanced prazosin-resistant pressor responses. These pressor responses were abolished by the P₂-purinoceptor antagonist suramin (300 µmol/L). The results demonstrate an increased ₂-adrenoceptor–mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels. ₁-Adrenoceptor–mediated transjunctional modulation of norepinephrine release by endogenous adenosine is defective in SHR kidneys and may be responsible for the greater norepinephrine release in this strain. Norepinephrine and ATP are coreleased in SHR and WKY kidneys and both mediate pressor responses to stimulation. The release of ATP is identical in SHR and WKY and is, like that of norepinephrine, modulated by ₂-adrenoceptor–mediated autoinhibition.

Key Words: hypertension, experimental • kidney • norepinephrine • purines • sympathetic nervous system • rats, inbred SHR • receptors, adrenergic, alpha • receptors, purinergic

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