nitroarginine and alpha-methylhistamine

1 The effect of histamine on the rate of lymphatic vessel constrictions and lymphatic smooth muscle membrane potential was examined in the guinea-pig mesentery. 2 Histamine (0.01-5 micro M) increased the frequency and decreased the amplitude of constrictions in lymphatic vessels under intraluminal perfusion. This response was accompanied by a depolarization of the smooth muscle membrane potential, an increase in the activity of spontaneous transient depolarizations (STDs), the proposed pacemaker for constrictions in these vessels, and an increase in the occurrence of action potentials. 3 Responses to histamine were inhibited by the H(1) receptor antagonist pyrilamine (0.2 micro M), but unaffected by NO synthase inhibition with N(G)-nitro L-arginine (L-NOARG, 100 micro M) and lysis of the endothelium. 4 In about 50% of the vessels, a decrease in constriction frequency, STD activity and a smooth muscle hyperpolarization were observed in response to dimaprit (10 micro M), suggesting the presence of H(2) receptors. These vessels had also a significantly lower basal contractile rate. Lymphatic vessel pumping was not affected by R-alpha-methylhistamine (10-50 micro M), ruling out a role for H(3) receptor stimulation in the histamine response. 5 The present results suggest a direct action of histamine on the lymphatic smooth muscle via stimulation of H(1) (and in some vessels H(2)) receptors. H(1) receptors enhance and H(2) receptors slow down lymphatic pumping, the dominant effect being an increased contractile activity. Correlation of these effects with histamine-induced changes in membrane potential and STD activity suggests the involvement of these electrical changes in the initiation of the contractile response.

Topics: Animals; Dimaprit; Dose-Response Relationship, Drug; Endothelium, Lymphatic; Female; Guinea Pigs; Histamine; Histamine Agonists; In Vitro Techniques; Lymphatic System; Male; Membrane Potentials; Mesentery; Methylhistamines; Muscle Contraction; Muscle, Smooth; Nitric Oxide; Nitroarginine; Receptors, Histamine H2; Receptors, Histamine H3

Nitric oxide synthase (NOS) and histamine H3 receptors are both markedly increased by neuronal injuries. To examine whether peripheral axotomy produced differential changes in NOS and H3 receptors, both NOS and H3 receptors were measured in the dorsal vagal complex after unilateral vagotomy. The presence of NOS-positive neurons was examined using both NADPH-diaphorase histochemistry and neuronal NOS-immunohistochemistry in rats vagotomized at the mid-cervical level. NADPH-diaphorase activity and NOS-immunoreactivity were markedly enhanced on the dorsal motor nucleus of the vagus (DMX) and in the ambiguous nucleus at the denervated side. Intraperitoneal injection of NOS inhibitors, N omega-nitro-L-arginine (10 mg/kg) or dexamethasone (0.5 mg/kg) attenuated the increase in NADPH-diaphorase activity. Glial fibrillary acidic protein (GFAP) was similarly induced 2 weeks after vagotomy in the vagal complex and surrounding area. Histamine H3 receptors in the vagal complex were visualized with [3H]N alpha-methylhistamine. The ligand-labeled H3 receptors were mainly located at the nucleus of the solitary tract (NST). The densities of H3 receptors did not change in the NST after unilateral vagotomy. These results suggest that peripheral axotomy such as mid-cervical vagotomy preferentially induces NOS in damaged neurons without affecting the level of H3 receptors.

Topics: Animals; Arginine; Brain; Dexamethasone; Functional Laterality; Histamine Agonists; Immunohistochemistry; Methylhistamines; Models, Neurological; NADPH Dehydrogenase; Neurons; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar; Receptors, Histamine H3; Time Factors; Vagotomy; Vagus Nerve

Intravenous injection of an H3-agonist, (R)-alpha-methylhistamine, dose-dependently caused a transient fall in mean arterial pressure of guinea-pigs. This pressor response was not reduced by combined mepyramine/cimetidine (up to 1 mg kg-1), atropine or propranolol, but was attenuated by either a selective H3-antagonist, thioperamide, or a competitive inhibitor of nitric oxide synthesis, NG-monomethyl L-arginine. The reduction by the inhibitor of nitric oxide synthesis was reversed by L- but not D-arginine. Histamine activated the H3-sites since its depressor response (obtained with mepyramine and cimetidine) was similar to that of (R)-alpha-methylhistamine. Our data indicate that H3-sites could exist in the cardiovascular system of guinea-pigs and that their stimulation might be mediated through the L-arginine/nitric oxide pathway.

Topics: Anesthesia; Animals; Arginine; Blood Pressure; Dose-Response Relationship, Drug; Guinea Pigs; Histamine; Histamine Agonists; Male; Methylhistamines; Nitric Oxide; Nitroarginine; Receptors, Histamine H3