Activation of histamine H₃ receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs

Abstract

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.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…Activation of H 3 receptors inhibits neurotransmission also in the peripheral autonomous and sensory systems. Sympathetic neurotransmitter release is regulated by H 3 receptor in guinea pig mesenteric artery (Ishikawa and Sperelakis, 1987), human saphenous vein (Molderings et al, 1992), guinea pig atria (Endou et al, 1994), human heart (Imamura et al, 1996), rat tail artery (Godlewski et al, 1997), and dog kidney (Yamasaki et al, 2001). Neuropeptide (tachykinins or calcitonin gene-related peptide) release from sensory C fibers from airways (Ichinose and Barnes, 1990), meninges (Matsubara et al, Fig.…”

Histamine receptors that influence blockage of the normal human nasal airway

“…Such a presynaptic effect of the H 3 receptor on sympathetic neurones has been reported many times in recent years (Molderings et al, 1992;Danko et al, 1994;Ishikawa & Sperelakis, 1999;Mazenot et al, 1999;Valentine et al, 1999;Blandizzi et al, 2000;Yamasaki et al, 2001;Silver et al, 2002;Varty & Hey, 2002). Increased blood flow to the nasal mucosa is largely responsible for nasal blockage and so reducing nasal mucosal blood flow Figure 7 The effect of thioperamide (Thio) on the nasal blockage caused by R-a-methylhistamine (R-a-MeH) (a) or two doses of histamine (Hist) (b and c) in the presence or absence of cetirizine (Cet).…”

Histamine receptor agonist alleviates severe cardiorenal damages by eliciting anti-inflammatory programming

“…For instance, in a rat model of isoproterenolinduced myocardial infarction, imetit, an H3 agonist, blunted the elevation of antioxidant markers and histopathological alterations in the heart (39). It has also been documented that (R)α-methylhistamine, another H3 agonist, inhibited kidney noradrenergic neurotransmission in anesthetized dogs (40). These examples imply that H3 agonists have a protective quality in cardiac and renal dysfunctions.…”