Alpha-adrenoceptor modulation of norepinephrine and ATP release in isolated kidneys of spontaneously hypertensive rats.
The present study investigates sympathetic cotransmission and its alpha-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 alpha 2-adrenoceptor antagonist rauwolscine (0.01 to 1 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in SHR than in WKY. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.03 to 3 mumol/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 mumol/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 mumol/L) markedly reduced pressor responses to stimulation and inhibited the induced ATP outflow by 60% to 70%. When prazosin (0.03 mumol/L) was present, rauwolscine (0.1 mumol/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 mumol/L). The results demonstrate an increased alpha 2-adrenoceptor-mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Bohmann
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C
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Germany.
Rump
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LC
Schaible
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U
von Kügelgen
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I
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000294:innervation / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013779:Tetrodotoxin; D013498:Suramin; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D009638:Norepinephrine; D011224:Prazosin