ALPHA-ADRENOCEPTOR MODULATION OF NOREPINEPHRINE AND ATP RELEASE IN ISOLATED KIDNEYS OF SPONTANEOUSLY HYPERTENSIVE RATS

The present study investigates sympathetic cotransmission and its alph a-adrenoceptor-mediated modulation in kidneys of spontaneously hyperte nsive rats (SHR, 12 to 14 weeks) and age-matched normotensive Wistar-K yoto rats (WKY). In the presence of cocaine and corticosterone, renal nerve stimulation at 1 Hz (30 seconds) induced a greater outflow of no repinephrine in SHR (4.2+/-0.2 pmol/g kidney) than in WKY (3.0+/-0.2 p mol/g kidney). The alpha(2)-adrenoceptor antagonist rauwolscine (0.01 to 1 mu mol/L) increased the stimulation-induced norepinephrine outflo w to a greater extent in SHR than in WKY. In contrast, the alpha(1)-ad renoceptor antagonist prazosin (0.03 to 3 mu mol/L) increased the stim ulation-induced norepinephrine outflow to a greater extent in WKY than in SHR. This difference was not observed in the presence of the P-1-p urinoceptor antagonist 8-(p-sulfophenyl)theophylline (100 mu mol/L). S timulation 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 mu mol/L) markedly reduced presser responses to stimulation and inhibited the induced AT P outflow by 60% to 70%. When prazosin (0.03 mu mol/L) was present, ra uwolscine (0.1 mu mo/L) increased the induced outflow of norepinephrin e and ATP and markedly enhanced prazosin-resistant presser responses. These presser responses were abolished by the P-2-purinoceptor antagon ist suramin (300 mu mol/L). The results demonstrate an increased alpha (2)-adrenoceptor-mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels. a lpha(1)-Adrenoceptor-mediated transjunctional modulation of norepineph rine release by endogenous adenosine is defective in SHR kidneys and m ay be responsible for the greater norepinephrine release in this strai n. Norepinephrine and ATP are coreleased in SHR and WKY kidneys and bo th mediate presser responses to stimulation. The release of ATP is ide ntical in SHR and WKY and is, like that of norepinephrine, modulated b y alpha(2)-adrenoceptor-mediated autoinhibition.