Obuchowicz R, Pawlik M W, Brzozowski T, Konturek S J, Pawlik W W
Department of Experimental Physiology, Jagiellonian University Medical College, Cracow, Poland.
J Physiol Pharmacol. 2004 Mar;55(1 Pt 2):255-67.
Data concerning cardiovascular effects of peripherally and centrally located histamine H(3) receptor stimulation are contradictory, and despite excessive studies their role in the control of the cardiovascular function have not been cleared yet. Effect of histamine H(3) receptors activation have been attributed to modulation of sympathetic system activity but exact role of peripherally and centrally located histamine H(3) receptors stimulation in the modulation of vascular tone of the mesentery and intestinal metabolism remains unexplored. Aim of the present study was to evaluate the role of centrally and peripherally located histamine H(3) receptors in the modulation of vascular tone of the mesentery and metabolic activity of intestinal tissue. In anesthetized rats total mesenteric blood flow (MBF), mucosal intestinal blood flow (LDBF), intestinal oxygen uptake (VO(2)) and arterial pressure (AP) were determined. Intestinal arterial conductance (C) was also calculated. Administration of the selective histamine H(3) receptor agonist imetit (10 micromol/kg i.a) evoked marked changes in hemodynamic and metabolic parameters; MBF, LDBF, C and VO(2) were significantly increased, whereas AP was significantly decreased. Pretreatment with histamine H(3) receptor antagonist clobenpropit (4 micromol/kg i.a.) abolished imetit-induced circulatory and oxygen uptake responses. Clobenpropit (4 micromol/kg i.a.) alone failed to affect the MBF, LDBF, AP, C and VO(2) values. Central administration of imetit (0.1 micromol i.c.v.) markedly increased AP and decreased MBF, LDBF, C and VO(2). Pretreatment with histamine H(3) receptor antagonist clobenpropit (0,4 micromol i.c.v.) diminished circulatory and metabolic responses to centrally injected imetit. Central histamine H(3) receptors blockade by clobenpropit evoked no significant changes in the mesenteric arterial and mucosal microcirculatory blood flow, intestinal metabolism and mean arterial pressure. We conclude that, peripheral histamine H(3) receptors when stimulated decreases vasoconstrictory tone of the mesenteric artery and precapillary structures and evokes increase of intestinal oxygen uptake. This might be in part due to inhibition of sympathetic postganglionic fibers vasopressor activity. Central histamine H(3) receptor stimulation activates vasoconstrictory sympathetic adrenergic system with possible involvement of other, presumably non-histaminergic receptors system. At basal conditions neither central nor peripheral histamine H(3) receptors are involved in the control of mesenteric macro- and microcirculation and intestinal oxygen consumption.
关于外周和中枢组胺H(3)受体刺激对心血管系统影响的数据相互矛盾，尽管进行了大量研究，但其在心血管功能调控中的作用仍未明确。组胺H(3)受体激活的作用归因于对交感神经系统活动的调节，但外周和中枢组胺H(3)受体刺激在调节肠系膜血管张力和肠道代谢方面的确切作用仍未得到探索。本研究的目的是评估中枢和外周组胺H(3)受体在调节肠系膜血管张力和肠道组织代谢活性中的作用。在麻醉大鼠中测定总肠系膜血流量(MBF)、肠黏膜血流量(LDBF)、肠道氧摄取量(VO(2))和动脉血压(AP)。还计算了肠动脉传导率(C)。给予选择性组胺H(3)受体激动剂碘替丁(10微摩尔/千克，腹腔注射)引起血流动力学和代谢参数的显著变化；MBF、LDBF、C和VO(2)显著增加，而AP显著降低。用组胺H(3)受体拮抗剂氯苯丙哌嗪(4微摩尔/千克，腹腔注射)预处理可消除碘替丁诱导的循环和氧摄取反应。单独给予氯苯丙哌嗪(4微摩尔/千克，腹腔注射)未能影响MBF、LDBF、AP、C和VO(2)值。中枢给予碘替丁(0.1微摩尔，脑室内注射)显著增加AP并降低MBF、LDBF、C和VO(2)。用组胺H(3)受体拮抗剂氯苯丙哌嗪(0.4微摩尔，脑室内注射)预处理可减弱对中枢注射碘替丁的循环和代谢反应。氯苯丙哌嗪对中枢组胺H(3)受体的阻断未引起肠系膜动脉和黏膜微循环血流量、肠道代谢和平均动脉压的显著变化。我们得出结论，外周组胺H(3)受体受到刺激时会降低肠系膜动脉和毛细血管前结构的血管收缩张力，并引起肠道氧摄取增加。这可能部分归因于对交感神经节后纤维血管升压活性的抑制。中枢组胺H(3)受体刺激激活血管收缩性交感肾上腺素能系统，可能涉及其他大概是非组胺能受体系统。在基础状态下，中枢和外周组胺H(3)受体均不参与肠系膜大循环和微循环以及肠道氧消耗的调控。
