Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys.
OBJECTIVE
In the present study, a rodent model was used to investigate whether the alpha(2A)-adrenoceptor (alpha(2A)) represents the presynaptic autoinhibitory receptor regulating sympathetic transmitter release in the kidney. Moreover, the potential role of alpha(2A) as a heteroceptor regulating adenosine triphosphate (ATP) release was tested.


METHODS
Kidneys from wild-type (WT) and alpha(2A)-knockout (KO) mice were isolated and perfused. Renal nerves were stimulated with platinum-electrodes. Endogenously released noradrenaline (NA) was measured by HPLC. The perfusion pressure was monitored continuously.


RESULTS
Renal nerve stimulation (RNS) induced a frequency (1,2,5,7.5,10,15 Hz)-dependent release of NA in WT mice (994+/-373, 2355+/-541, 6375+/-950, 11626+/-1818, 19138+/-2001 pg NA g(-1) kidney (means+/-s.e.m.)). There was a 2.7-fold (5 Hz) increase of NA release in alpha(2A)-KO mice. In WT animals alpha-adrenoceptor blockade by phentolamine increased RNS-induced NA release in a concentration-dependent manner up to 350% of control. No facilitation by phentolamine was observed in alpha(2A)-KO mice. Pressor responses to 1 Hz and 2 Hz were resistant to alpha(1)-adrenoceptor blockade (0.03 microM prazosin) but abolished by P(2) receptor blockade (5 microM PPADS). Blockade of alpha(2)-adrenoceptors (1 microM rauwolscine) increased these purinergic pressor responses to 296+/-112% (1 Hz) in WT but not in alpha(2A)-KO mice. Exogenous ATP (100 microM) increased basal but not RNS-induced NA release.


CONCLUSIONS
alpha(2A)-Adrenoceptor-activation inhibits NA and ATP release from renal sympathetic nerves. Pressor responses to RNS at higher stimulation frequencies (>2 Hz) are mediated by NA. At lower frequencies neuronally released ATP seems to be the predominant transmitter mediating renovascular resistance.
Vonend
O
O
Department of Nephrology, Marienhospital Herne, Herne, Ruhr-University Bochum, Germany.
Habbel
S
S
Stegbauer
J
J
Roth
J
J
Hein
L
L
Rump
L C
LC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*
C547769:Adra2a protein, mouse; D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D000255:Adenosine Triphosphate