Nitric oxide inhibition of renal vasoconstrictor responses to sympathetic cotransmitters in the pig in vivo.
The object of the present study was to investigate the involvement of nitric oxide (NO) in the regulation of renal vasoconstrictor responses to sympathetic nerve activation, and each of the known sympathetic cotransmitters separately, in the pig in vivo. Renal vasoconstrictor responses were elicited by sympathetic nerve stimulation, the alpha(1)-adrenoceptor agonist phenylephrine (10 nmol kg(-1), injected iv), neuropeptide Y (NPY, 120 pmol kg(-1), iv) acting on the NPY Y(1) receptor, and the stable ATP-analogue alpha,beta-methylene ATP (mATP, 10 nmol kg(-1)) presumably acting on the P2X(1) purinoceptor. Infusion of the NO-donor sodium nitroprusside, at a dose (0.1 mg kg(-1) h(-1), iv) that elevated renal blood flow (by 14 +/- 7%) and lowered mean arterial pressure (by 30 +/- 5%), inhibited renal vasoconstrictor responses to sympathetic nerve stimulation, phenylephrine, and NPY, but not to mATP. In contrast, injection of the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, at a dose (10 mg kg(-1), iv) that lowered renal blood flow (by 47 +/- 4%) and elevated mean arterial pressure (by 28 +/- 8%), potentiated the renal vasoconstriction evoked by sympathetic nerve stimulation, phenylephrine, and NPY, but not mATP. It is concluded that endogenous NO may function as an inhibitory modulator of vasoconstrictor responses to the sympathetic cotransmitters norepinephrine and NPY. In contrast, NO seems not to modify vasoconstrictor responses to the sympathetic cotransmitter ATP, a discrepancy that may be due to differences in the types of receptors and intracellular effector mechanisms.
Malmström
R E
RE
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. rickard.malmstrom@fyfa.ki.se
Björne
H
H
Alving
K
K
Weitzberg
E
E
Lundberg
J O
JO
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013552:Swine / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D009478:Neuropeptide Y; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester