Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs.
To investigate the possible involvement of histamine H(3) receptors in renal noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor antagonist, on renal nerve stimulation (RNS)-induced changes in renal function and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5-2.0 Hz) produced significant decreases in urine flow and urinary sodium excretion and increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When R-HA (1 microg x kg(-1) x min(-1)) was infused intravenously, mean arterial pressure and heart rate were significantly decreased, and there was a tendency to reduce basal values of urine flow and urinary sodium excretion. During R-HA infusion, RNS-induced antidiuretic action and increases in NEOR were markedly attenuated. Thiop infusion (5 microg x kg(-1) x min(-1)) did not affect basal hemodynamic and excretory parameters. Thiop infusion caused RNS-induced antidiuretic action and increases in NEOR similar to the basal condition. When R-HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate the RNS-induced antidiuretic action and increases in NEOR. However, in the presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced actions, similarly to the case without these antagonists. Thus functional histamine H3 receptors, possibly located on renal noradrenergic nerve endings, may play the role of inhibitory modulators of renal noradrenergic neurotransmission.
Yamasaki
T
T
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Tamai
I
I
Matsumura
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D004574:Electromagnetic Fields; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D009412:Nerve Fibers / Q000502:physiology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000652:urine; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology*
D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D012964:Sodium; C052075:thioperamide; D009638:Norepinephrine