Effects of activation of central nervous histamine receptors in cardiovascular regulation; studies in H(1) and H(2) receptor gene knockout mice.
To elucidate the central roles of histamine receptors in cardiovascular regulatory system, systolic, mean, and diastolic blood pressures (BPs) and heart rate (HR) were examined in conscious H(1) receptor gene knockout (H(1)KO) mice, H(2) receptor gene knockout (H(2)KO) mice, H(1) and H(2) receptor gene double knockout (DKO) mice, and their respective control mice by the tail-cuff system. Histamine, histamine-trifluoromethyl-toluidine derivative (HTMT, an H(1) agonist), dimaprit (an H(2) agonist), and immepip (an H(3) agonist) were intrathecally administered to these KO mice and control mice. Basal BPs and HR were not different among these three KO mice and their control or wild-type mice. Intrathecal administration of histamine significantly increased BPs and decreased HR in control mice. The increases in BPs were produced by histamine in H(1)KO and H(2)KO mice and by HTMT and dimaprit in C57BL mice. The pressor responses by HTMT and dimaprit in C57BL mice were greater than those by histamine in H(1)KO and H(2)KO mice, although the same decreases in HR were induced by histamine in C57BL and H(1)KO mice and by dimaprit in C57BL mice. The selective stimulation of H(3) receptors by immepip produced a consistent decrease in BPs in control mice. These results obtained with the exogenous selective agonists of three histamine receptors suggest that the pressor responses to histamine are mediated through the stimulation of both H(1) and H(2) receptors, whereas the atropine-sensitive decrease in heart rate is mainly due to H(2) receptors which activate the vagal output to the heart.
Suzuki
Hideaki
H
Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Aoba-ku, Sendai 980-8575, Japan.
Mobarakeh
Jalal Izadi
JI
Nunoki
Kazuo
K
Sukegawa
Jun
J
Watanabe
Haruo
H
Kuramasu
Atsuo
A
Watanabe
Takeshi
T
Yanai
Kazuhiko
K
Yanagisawa
Teruyuki
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D017259:Dimaprit / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011968:Receptors, Histamine / Q000235:genetics*
D017442:Histamine Agonists; D007093:Imidazoles; D010880:Piperidines; D011968:Receptors, Histamine; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D006632:Histamine; D017259:Dimaprit
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