Effect of substance P administration on vascular permeability in the rat oral mucosa and sublingual gland.

Neuropeptides, including substance P (SP) may play a role in neurogenic inflammation. Although SP-immunoreactive (SP-IR) axons are known to be present within the oral mucosa (OM) and salivary glands, the functional significance of SP in oral mucosa and sublingual salivary gland (SLG) is not fully understood. The present experiments were carried out to study the effects of SP infused into the left common carotid artery on vascular permeability in the OM and in the SLG of male rats. Vascular permeability was assessed on the basis of Evans Blue extravasation. Separate groups of animals received histamine (H1) receptor antagonist (chloropyramine, 10 mg kg-1 i.v.) or prostaglandin synthesis inhibitor (indomethacin, 4 mg kg-1 i.v.) prior to SP infusions. Infusion of SP in doses of 30 and 74 pmol min-1 increased the vascular permeability of OM by 162.3 +/- 16.3% (n = 8, p < 0.05) and 482.7 +/- 46.7% (n = 8, p < 0.001), respectively. SP in a dose of 15 pmol min-1 did not increase Evans Blue extravasation in OM (38.3 +/- 4.0 micrograms g-1, n = 8, compared to the control: 44.0 +/- 7.9 micrograms g-1, n = 8, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of substance P (SP) in development of symptoms of neurogenic inflammation in the oral mucosa of the rat.

In the present series of investigations we first studied the local effects of exogenous substance P (SP) on the hallmarks of neurogenic inflammation, i.e. vascular permeability and blood flow, in the oral mucosa of the rat. Pretreatment with capsaicin was shown to attenuate the symptoms of neurogenic inflammation; therefore, the distribution of nerve fibers displaying substance P-like immunoreactivity (SP-IR) in the mandibular mucosa was also assessed in control rats and in animals pretreated with capsaicin both neonatally and in adulthood using immunohistochemical techniques. The application of SP at a dose of 7.5 nmol resulted in an almost 70% increase of vascular permeability (NS) and the administration of a four-fold higher dose (30 nmol) produced about 150% increase in Evans blue extravasation compared with control values (p < 0.05). A similar increase (ca 146%) in vascular permeability was observed in response to 45 nmol SP solution (p < 0.05). While the 7.5 nmol SP-solution failed to affect blood flow, the 30 nmol SP significantly increased it by ca. 38% (p < 0.05). The administration of the 45 nmol SP solution resulted in a similar enhancement of blood flow (43%, p < 0.05). Capsaicin pretreatment performed either neonatally or in adulthood has reduced the number of SP-immunoreactive fibers in the oral mucosa. Our functional results suggest that SP may have a role in the experimentally-induced neurogenic inflammation of the oral mucosa in the rat. This is also supported by our finding that capsaicin pretreatment, known to decrease the number of SP-immunoreactive fibers in these tissues, reduced the symptoms of neurogenic inflammation.

Effect of substance P administration on vascular permeability in the rat dental pulp and submandibular gland.

The effects of substance P (SP) administration on vascular permeability were studied in the dental pulp (DP) of upper and lower incisors and in the submandibular gland (SMG) of male rats. Vascular permeability was assessed by means of extravasation of Evans blue dye. SP was diluted in 0.5% bovine serum albumin (BSE) and infused into the left common carotid artery. Separate groups of animals receive chloropyramine, an H1 histamine receptor antagonist (10 mg kg-1 i.v.) or indomethacin, a prostaglandin synthesis inhibitor (4 mg kg-1 i.v.) prior to SP infusions. Infusion of SP for 5 min increased plasma extravasation both in DP and SMG, with a threshold of about 30 pmol min-1 and 74 pmol min-1, respectively. Enhanced salivary secretion was also observed. Although the administration of 74 pmol min-1 of SP significantly lowered the systemic blood pressure, experimental hypotension elicited by haemorrhage did not influence vascular permeability in either organ tested. After chloropyramine administration the SP effect on vascular permeability in both DP and SMG was abolished. Indomethacin pretreatment failed to prevent the permeability-enhancing action of SP. Our results suggest that substance P increases both pulpal and glandular plasma extravasation in the rat indirectly, via the release of histamine and the activation of H1 histamine receptors.

[The role of histamine in neurogenic inflammations of the mouth mucosa in rats]. / A hisztamin szerepe a patkány-szájnyálkahártya neurogén inflammációjában.

The effect mechanism of neurogen inflammation incited by local capsaicin irritation was examined by the authors in the oral soft tissue of rats subsequent to antihistamin pretreatment. Furthermore, with the aid of muscarin blocking receptor also the parasympathetic component of the vasodilatation was examined. On basis of their results it was established that the vein-wall-permeability and microcircular changes observed in the course of the neurogen inflammation of the oral soft tissue partly expanded by the histamin through the H1-receptors. The H2-receptors as well as the parasympathetic fibers do not become activated in the process.

Role of histamine in the development of neurogenic inflammation of rat oral mucosa.

The mechanism of development of neurogenic inflammatory reaction induced by the topical application of capsaicin was studied in the oral mucosa of rats with or without histamine antagonist pretreatment. The existence of a cholinergic component of the vasodilation was investigated using a muscarinic receptor antagonist. Results indicated that the neurogenic inflammatory increases in vascular permeability and blood flow are mediated in part by H1-receptors, H2-receptors and cholinergic pathways are apparently not activated in these processes.