The role of endothelial nitric oxide in the Substance P induced vasodilation in bovine dental pulp

Vasodilation, an important response in neurogenic inflammation, involves release of Substance P (SP) from the sensory nerve endings. It is now well known that SP causes edema formation and vascular relaxation in nondental tissues, however, the SP vasodilatory mechanism in the dental pulp is not completely understood. Endothelium-dependent relaxation is mediated by nitric oxide (NO) release with consecutive intracellular cyclic-GMP elevation in many vascular preparations. Recently, it has been shown in different vascular systems that SP-induced vasodilation is mediated by cyclic-GMP production through different pathways involving endothelial NO or direct endothelial-independent pathways. In the present study, the role of endothelial NO in SP induced vasodilation in the dental pulp was investigated to better understand the inflammatory mechanisms. Freshly extracted bovine dental pulp was used to measure NO production. Sodium nitroprusside (SNP), L-NAME and SP were utilized to induce and to inhibit NO production in endothelial cells. Released NO byproducts were measured with chemiluminescence assay technique. The present data demonstrate that SP induces NO production by activating NOsynthase (NOS) in endothelial cells. The NOS inhibitor L-NAME blocks NO production completely. In conclusion, in the bovine dental pulp, SP-induced vascular relaxation can be mediated by inducing NOS, and subsequently NO production in endothelial cells.     

Effect of iontophoretical application of NK1 receptor antagonists on pulpal blood flow in cats

The influence of NK1 receptor antagonists applied iontophoretically on pulpal blood flow (PBF) was investigated. Along with substance P (SP, 0.8 approximately 20.0 ng/kg) administration to the canine pulp through the catheterized lingual artery, two NK1 receptor antagonists, [D-Pro2,D-Trp7,9]-SP and [D-Pro2,D-Phe7,D-Trp9]-SP (0.2 approximately 3.4 mM) were applied iontophoretically (cathodal current, 0.02 approximately 0.1 mA, 1 min) to the prepared class V dentinal cavity of ipsilateral teeth in 11 generally anesthetized cats. A paired t-test showed that SP administration caused significant increases of PBF (p < 0.05) without changing systemic blood pressure, and that SP and SP antagonist administration caused significantly less increase of PBF than in control of SP and 0.9% saline administration (p < 0.05). These data provide evidence that the iontophoretic application of NK1 receptor antagonists effectively attenuates SP-induced vasodilatation and show the possibility of their use in the control of neurogenic inflammation in the dental pulp.     

Effect of the sensory neuropeptide antagonists h-CGRP((8-37)) and SR 140.33 on pulpal and gingival blood flow in ferrets

In a previous study, it was concluded that the neuropeptides calcitonin gene-related peptide (CGRP) and substance P are released during resting conditions in the (exposed) ferret dental pulp, contributing to a basal vasodilator tone in the pulpal vessels. In order to exclude the possibility that the method used elicited axon reflexes, which might be responsible for neuropeptide release, the present study was designed without pulp exposure. Non-invasive laser-Doppler flowmetry was used to measure the effects of intra-arterial infusions of the antagonists h-CGRP((8-37)) and SR 140.33 (neurokinin 1-receptor antagonist) on pulpal and gingival blood flow before, during and after electrical tooth stimulation. Infusions of h-CGRP((8-37)) reduced the basal blood flow in the pulp by 31.4+/-5.2% (p<0.001) and in the gingiva by 22.6+/-4.8% (p<0.05). A further significant decrease in basal blood flow was measured in both pulp and gingiva following SR 140.33 administration. The reduction in blood flow was 16.9+/-1.9% (p<0.005) in the pulp and 19. 3+/-5.6% (p<0.05) in the gingiva. The systemic arterial pressure remained unchanged both during and after the periods of infusion. Tooth stimulation before the antagonist infusion significantly increased the pulpal blood flow by 71.9+/-15.3% (p<0.005). Infusion of h-CGRP((8-37)) greatly reduced this electrically induced vasodilatation, indicating that CGRP is the principal factor responsible for the vasodilatation observed after tooth stimulation. This study confirms the previous finding that a resting vasodilator tone due to the release of CGRP and SP exists in the ferret dental pulp. It is concluded that spontaneous, basal release of the neuropeptides CGRP and substance P exists both in dental pulp and gingiva in the ferret.     

Calcitonin gene related peptide: a sensory transmitter in dental pulps?

Nerve fibers displaying calcitonin gene related peptide (CGRP) immunoreactivity occurred in dental pulps of several mammals, including man. The CGRP fibers were more numerous in the apical parts than in the coronal parts and were distributed around small blood vessels as well as in the pulpal stroma without any obvious relation to blood vessels. The trigeminal, spinal and jugular-nodose ganglia harbored a moderate supply of CGRP immunoreactive perikarya and nerve fibers. Immunocytochemic double staining revealed the coexistence of CGRP and SP in a population of perikarya in the sensory ganglia and suggested coexistence of the two peptides in perivascular nerve fibers in the cat dental pulp. The cervical sympathetic ganglia did not contain CGRP-immunoreactive perikarya. Cervical sympathectomy (studied in the guinea-pig and rat) did not affect the frequency or distribution of pulpal CGRP fibers. The distribution of CGRP fibers within the dental pulp and the presence of CGRP perikarya in sensory ganglia known to supply the dental pulps indicate that the pulpal CGRP fibers are sensory in nature and that CGRP together with SP may participate in the regulation of local blood flow and the response to local inflammation.     

Calcitonin gene related peptide: a sensory transmitter in dental pulps?

Abstract — Nerve fibers displaying calcitonin gene related peptide (CGRP) immunoreactivity occurred in dental pulps of several mammals, including man. The CGRP fibers were more numerous in the apical parts than in the coronal parts and were distributed around small blood vessels as well as in the pulpal stroma without any obvious relation to blood vessels. The trigeminal, spinal and jugular-nodose ganglia harbored a moderate supply of GGRP immunoreactive perikarya and nerve fibers. Immunocytochemic double staining revealed the coexistence of CGRP and SP in a population of perikarya in the sensory ganglia and suggested coexistence of the two peptides in perivascular nerve fibers in the cat dental pulp. The cervical sympathetic ganglia did not contain CGRP-immnunoreactive perikarya. Cervical sympathectomy (studied in the guinea-pig and rat) did not affect the frequency or distribution of pulpal CGRP fibers. The distribution of CGRP fibers within the dental pulp and the presence of CGRP perikarya in sensory ganglia known to supply the dental pulps indicate that the pulpal CGRP fibers are sensory in nature and that CGRP together with SP may participate in the regulation of local blood flow and the response to local inflammation.     

NO-cGMP signaling molecules in cells of the rat molar dentin-pulp complex

By the formation of cyclic guanosine 3',5'-monophosphate (cGMP), nitric oxide (NO)-sensitive enzyme-soluble guanylate cyclase (sGC) plays a receptor role for NO within the NO-cGMP signaling cascade, which is involved in vasodilatation and neurotransmission. The hypothesis that NO-cGMP signaling molecules modulate cells of the dentin-pulp complex was investigated in rat molars by histochemical, immunohistochemical, immuno-ultrastructural, and organ bath techniques. NO synthase (NOS) I-III, the sGC alpha(2)-subunit/beta(1)-subunit, and cGMP were detected in odontoblasts and blood vessels. NOS I, sGC alpha(2), and cGMP were identified in nerve fibers. Treatment of rat molars with the NO donor NONOate (10(-5) M) increased cGMP staining intensities in blood vessels and odontoblasts, while NO synthase inhibitor L-NAME (10(-4) M) attenuated intensity of the reaction products for cGMP, suggesting an effect of endogenous NO on sGC. These correlations of patterns and alterations of cGMP staining intensities after treatment with the NO donor or NO inhibitor might represent an NO-sGC-cGMP signaling-dependent modulation of odontoblasts, blood vessels, and nerve fibers in the dentin-pulp complex.     

Involvement of nitric oxide in orthodontic tooth movement in rats.

Nitric oxide (NO) is an important regulatory molecule in bone formation and resorption. The purpose of this study was to examine the role of NO in orthodontic tooth movement in rats. We used specific inhibitors of NO synthases (NOS). Upper first molars of 9-week-old male Wistar rats were moved buccally for 21 days. The local administration of N(G)-nitro-L-arginine methyl ester. HCl (L-NAME), a general inhibitor of NOS activity, significantly reduced tooth movement. On the other hand, N(6)-(1-iminoethyl)-L-lysine. 2HCl (L-NIL), a selective inhibitor of the inducible isoform of NOS, had no effect. These results suggest that NO is an important biochemical mediator in the response of periodontal tissue to orthodontic force and is produced primarily through the activity of constitutive NOS.     

Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth

AIM: The purpose of this study was to investigate the levels of substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) in painful and healthy human dental pulps. METHODOLOGY: Forty-six samples of pulp tissue were collected from extracted or endodontically treated painful teeth and 20 from clinically healthy teeth extracted for orthodontic reasons. All pulp samples were boiled in 0.5 m acetic acid for 10 min, centrifuged and the supernatant collected. SP, NKA and CGRP levels were measured using radioimmunoassay. RESULTS: Substance P and CGRP were present in all samples and NKA was detected in 96% of the pulps. CGRP was present in much higher concentrations than SP and NKA in both painful and non-painful teeth. The painful teeth had significantly higher concentrations of SP (P = 0.02), NKA (P < 0.001) and CGRP (P = 0.03) than non-painful teeth. The concentration of CGRP was significantly higher in the pulps of smokers compared with non-smokers (P = 0.02). CONCLUSIONS: Elevated levels of these neuropeptides in pulps from painful teeth indicate that they may play an important role in the process of pulpal inflammation and pain. Further investigation of the association between these neuropeptides and pulpal status may help to improve our understanding of pulpal inflammation and dental pain.     

Interaction between the autonomic and sensory nerves in the dental pulp

The function of intradental sensory receptors is strongly affected by activation of the sympathetic nerves. This effect is most probably indirect and due to changes in pulpal blood flow. Also, in inflamed teeth the sensitivity changes of pulp nerves seem to be closely related to changes in the blood flow. Such inflammatory mediators as histamine, bradykinin and serotonin affect the sensitivity of intradental receptors in pulpal inflammation. In addition, many neuropeptides, for example substance P (SP) and calcitonin gene-related peptide (CGRP), seem to be involved and may interact with histamine or bradykinin. Recent studies indicate that intradental nerves with their neuropeptides may play a significant role in the inflammatory and defence reactions of the dental pulp.     

牙髓损伤性刺激对牙髓组织中P物质等的影响

目的：比较和分析急性牙髓炎和牙齿开髓刺激后，牙髓组织中Ｐ物质（ＳＰ）、降钙素基因相关肽（ＣＧＲＰ）的变化。方法：利用免疫组织化学方法观察大鼠牙齿开髓后２ｈ、４ｈ和急性牙髓炎２ｈ、４ｈ组牙髓组织中ＳＰ、ＣＧＲＰ免疫阳性纤维的变化。结果：牙髓炎性及机械损伤性伤害刺激引起牙髓组织ＳＰ／ＣＧＲＰ免疫阳性纤维一致性变化。牙齿开髓及牙髓炎２ｈ、４ｈ组牙髓组织中ＳＰ、ＣＧＲＰ免疫阳性纤维减少。结论：两种刺激均引起牙髓组织内神经末梢释放ＳＰ、ＣＧＲＰ。     

Nitric oxide synthase activity in neutrophils from patients with localized aggressive periodontitis

BACKGROUND: Localized aggressive periodontitis (LAgP) is associated with neutrophil dysfunction including defective chemotaxis and reduced calcium influx factor activity. Nitric oxide (NO) and its enzyme, nitric oxide synthase (NOS), have been suggested to be involved in chemotaxis. Some reports, however, were unable to detect either NO or NOS in human neutrophils. In this study, we focused on NOS activity in LAgP neutrophils and examined the involvement of NOS in chemotaxis of normal neutrophils and NOS activity in neutrophils from normal subjects and patients with LAgP. METHODS: Neutrophils from 10 normal subjects and 10 LAgP patients were isolated from peripheral venous blood. Membrane associated-NOS (MA-NOS) and soluble NOS (S-NOS) were extracted from cells with or without FMLP stimulation. NOS activity was measured using the radiolabeled L-arginine to L-citrulline conversion assay. RESULTS: N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly inhibited FMLP-induced chemotaxis (P<0.01) and dibutyryl cGMP, an activator of cGMP-dependent protein kinase, significantly attenuated the inhibition by L-NAME (P<0.01). Unstimulated and FMLP-stimulated MA-NOS activity in LAgP neutrophils was statistically significantly higher than that in normal neutrophils (P<0.05). S-NOS activity in LAgP neutrophils was higher than that in normal neutrophils. CONCLUSIONS: This study suggests that NOS is present in human neutrophils and may be involved in FMLP-induced chemotaxis in normal neutrophils. NOS activity is increased in LAgP and is negatively correlated to chemotaxis response.     

Comparison of the effects of intra-arterial and locally applied vasoactive agents on pulpal blood flow in dog canine teeth determined by laser Doppler velocimetry

The vasoactive agents norepinephrine, 5-hydroxytryptamine, isoproterenol and bradykinin, at concentrations which changed local arterial pressure without changing systemic arterial pressure significantly, were injected intra-arterially (i.a.) into the maxillary artery or applied directly in a deep dentinal cavity on the buccal surface of canine teeth. The probe of a laser Doppler velocimeter was placed in the cavity to monitor pulpal blood flow. Bolus i.a. injections of the vasoconstrictors norepinephrine and 5-hydroxytryptamine produced a statistically significant (p less than 0.05) reduction in pulpal blood flow, 21.1 +/- 3.7 and 30.7 +/- 15.2%, and the local arterial pressure from the lateral nasal artery increased with norepinephrine but decreased with 5-hydroxytryptamine. The i.a. injections of the vasodilators isoproterenol and bradykinin were found to decrease both local arterial pressure and pulpal blood flow, 17.7 +/- 6.0 and 22.7 +/- 4.2%, respectively (p less than 0.05). However, local application of isoproterenol and bradykinin caused a biphasic response: an increase in pulpal blood flow, 8.6 +/- 1.6 and 9.4 +/- 1.1% (p less than 0.05), followed by a decrease, 19.1 +/- 11.9 and 5.3 +/- 2.1% (p greater than 0.005). Local application of norepinephrine and 5-hydroxytryptamine caused a decrease in pulpal blood flow, 23.7 +/- 5.2% (p less than 0.05) and 9.3 +/- 5.2% (p less than 0.05), respectively. These findings were in accordance with those from other reliable methods, such as injections of radioisotope-labelled 15 microns microspheres and the 133Xe washout technique, making laser Doppler flowmetry a reliable alternative. In addition, the biphasic response to the locally applied vasodilators and the reduction of pulpal blood flow after i.a. injection of vasodilators suggest that regulation of pulpal blood flow is determined by the combined effects of the low compliance environment and the stealing of perfusion to the pulp by the neighbouring tissues.     

In vitro effects of nitric oxide synthase inhibitor L-NAME on oral squamous cell carcinoma: a preliminary study

It has been reported that increased nitric oxide synthase (NOS) expression and nitric oxide (NO) production may play an important role in cancer biology. The aim of this study was to determine the roles of NO in tumour cellular proliferation and DNA or RNA synthesis, and to investigate the therapeutic potential of NOS inhibitors in oral cancer. After exposure to different concentrations of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the growth of TSCCa cells, established from a patient with squamous cell carcinoma of the tongue, was evaluated using MTT and crystal violet assay. DNA or RNA synthesis, inducible/endothelial NOS (iNOS/eNOS) mRNA expression and NO production were then examined to determine the possible mechanisms of inhibitory effects of L-NAME on TSCCa cells. L-NAME had an inhibitory effect on TSCCa cell growth in both a concentration- and time-dependent manner. Acridine orange staining revealed that DNA and/or RNA synthesis of TSCCa cells was reduced after treatment with L-NAME. An in situ hybridisation (ISH) study showed clearly that L-NAME down-regulated eNOS and iNOS mRNA expression and this was followed by a decrease in NO production. It is postulated that the NOS/NO pathway may be implicated in cellular proliferation and DNA or RNA synthesis of cancer cells, apart from promoting tumour angiogenesis. Further studies have provided with new insight into the mechanisms by which NOS/NO takes part in oral carcinogenesis, and possible therapeutic interventions based on the NOS/NO pathway for tumour progression control.     

Pulpal exposure alters neuropeptide levels in inflamed dental pulp and trigeminal ganglia: evaluation of axonal transport

Dental pulp is richly innervated with neurons containing calcitonin gene-related peptide (CGRP) or substance P (SP). Prior studies have demonstrated that inflammation alters these pulpal neuropeptides. In this study, we used a radioimmunoassay to evaluate the specificity of this response and the contribution of axonal transport. Rat mandibular molars were exposed and immunoreactive CGRP (iCGRP) and immunoreactive SP were measured. At 7 to 14 days after exposure, both pulpal iCGRP (73%) and immunoreactive SP (135%) displayed peak increases above control levels. This response was somatotopically restricted, with no changes observed in contralateral (intact) molars, or in ipsilateral mandibular molars after exposure of maxillary molars. Transection of the inferior alveolar nerve on day 13 significantly reduced pulpal levels of iCGRP on day 14. Collectively, these studies indicate that pulpal inflammation evokes a selective alteration in neuropeptide levels, due at least in part to alterations in transport or synthesis of neuropeptides in the trigeminal ganglion.     

The role of sensory neuropeptides and nitric oxide on pulpal blood flow and tissue pressure in the ferret.

A study was designed to investigate the effects of close intra-arterial infusion of antagonists to the sensory neuropeptides calcitonin gene-related peptide and substance P, as well as the effect of the nitric oxide synthesis inhibitor L-NAME on pulpal blood flow and interstitial fluid pressure during resting conditions and after electrical tooth stimulation. The micropuncture technique was used to measure tissue pressure and laser-Doppler flowmetry for blood flow recordings in ferret canine teeth. Close intra-arterial infusion of antagonists to calcitonin gene-related peptide and substance P significantly reduced resting blood flow (p < 0.05) and interstitial fluid pressure (p < 0.005) by unchanged systemic arterial pressure, while L-NAME administration caused a significant rise in interstitial fluid pressure (p < 0.05) and systemic arterial pressure (p < 0.005), with a concomitant fall in resting blood flow (p < 0.005). Tooth stimulation after calcitonin gene-related peptide antagonist infusion gave no significant change in blood flow or interstitial fluid pressure, whereas substance P antagonist infusion only partly eliminated the vasodilator response. L-NAME had no effect on the vasodilation induced by tooth stimulation. It is concluded that a resting vasodilator tone due to release of calcitonin gene-related peptide, substance P, and nitric oxide exists in the ferret dental pulp. The sensory neuropeptides exert their effect predominantly on pre-capillary vessels, and nitric oxide predominantly on post-capillary vessels. The sensory neuropeptide calcitonin gene-related peptide seems to be mainly responsible for the increase in blood flow and interstitial fluid pressure during tooth stimulation, whereas there was no evidence that nitric oxide participates in the vasodilation induced by tooth stimulation.     

Effects of an inducible nitric oxide synthase inhibitor on experimentally induced rat pulpitis

Nitric oxide (NO) is a biological effector molecule involved in a large variety of reactions and, as synthesized by inducible nitric oxide synthase (iNOS), has many important roles in inflammatory conditions. This study aimed to evaluate the anti-inflammatory effects of an iNOS-specific inhibitor, N-(3-(aminomethyl)benzyl)acetamidine (1400W), on experimentally induced rat pulpitis in the upper incisors of 6-wk-old male Wistar rats. 1400W (1 mg kg(-1)), the non-specific NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1)), or sterile saline (control) were administered before the application of lipopolysaccharide (LPS). Rats were killed 3, 6, 9, 12, 24, 48, and 72 h after LPS application, and immunocompetent cells were detected immunohistochemically. The numbers of granulocytes infiltrating into the pulp were significantly depressed in the 1400W group compared with the saline and L-NAME groups. The kinetics of the macrophages and Ia(+) cells in the 1400W group were similar to those in the L-NAME group, while the maximum numbers in both groups were significantly reduced compared with those in the saline group. These results suggest that NO may be responsible for the infiltration of immunocompetent cells in the progress of pulpitis, and that 1400W is a promising candidate for controlling pulpal inflammatory reactions.     

The role of nitric oxide in orthodontic tooth movement in rats

Nitric oxide (NO) is involved in second messenger formation, osteoblast and osteoclast function, and pulpal blood flow. This raises the question of whether or not altered NO production interferes with orthodontic tooth movement (OTM) by influencing the bone remodeling cycle. To investigate the role of NO in OTM, a rat model was established and 48 rats were divided into four study groups of 12 rats each. A 5 mm nickel-titanium closed-coil spring was ligated between the right maxillary incisor and first molar of each rat to deliver an initial force of 60 g. A saline group received subperiosteal injections of normal saline (50 microL/kg), an L-arginine (L-arg) group received L-arginine (NO precursor) injections (200 mg/kg), and a, L-NAME group received N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor)(10 mg/kg) injections. All injections were given in the upper right first molar mucosa from the first through the 11th day of force application at 48-hour intervals. A control group received no injections. Tooth movement measurements were done at the time of injections. Animals were sacrificed 13 days after appliance insertion and final OTMs were measured at the time of sacrifice. From the third day till the end of the experiment, the L-arg group showed a significant increase in tooth movements, whereas the L-NAME group showed a significant decrease in tooth movements compared to the control and saline group (P < .001). Histopathologic studies revealed that the number of osteoclasts was significantly higher in the L-arg group smears, while the number of osteoclasts in the L-NAME group was significantly lower as compared to the control group (P < .001). Scanning electron microscope analysis showed that the force-induced root resorption in the L-arg group was less than the control group. This study suggests a role for NO in the bone remodeling cycle.     

Effects of systemic and topical nicotine on pulpal blood flow in dogs

Abstract It has been suggested that nicotine exerts cardiovascular effects which are similar to stimulation of the sympatho-adrenal system. If this observation is true, nicotine administration would decrease pulpal blood flow and possibly alter the pulpal response to injury. The purpose of this study was to measure pulpal blood flow in dogs using the radiolabelled microsphere method following topical or systemic administration of nicotine for 28 days. Thirteen dogs were divided into three groups. Group one received topical nicotine (8 mg nicotine/kg/day) combined with orabase which was applied in two equal doses to the mandibular anterior gingiva. Group two received systemic nicotine (2.5 mg/kg/day) delivered by osmotic pumps implanted subcutaneously in the back of each animals' neck. Group three were controls, and these animals received either topical orabase twice daily applied to the mandibular anterior gingiva or saline via osmotic pumps. Results indicated pulpal blood flow increased from Day 0 to Day 28 in both nicotine treated groups. Group one (topical nicotine) exhibited a mean increase in blood flow of 21.8 ml/min/100 g. while group two exhibited a mean increase of 50.1 ml/min/100 g. Group three, the control animals, exhibited a mean decrease in pulpal blood flow of 22.1 ml/min/100 g over the 28-day interval. These changes were not statistically significant (p > 0.05).     

An in vivo and in vitro comparison of the effects of vasoactive mediators on pulpal blood vessels in rat incisors

The effects of endogenous vasoactive substances were evaluated in anaesthetized rats using a laser Doppler flowmeter to monitor changes in pulpal blood flow, as well as directly in isolated pulpal arteriole preparations utilising a microperfusion and monitoring system to observe changes in vessel diameter. In anaesthetized rats, while systemic arterial blood pressure remained relatively stable, intra-arterial delivery of adrenaline (epinephrine) (A), noradrenaline (norepinephrine) (NA), phenylephrine (PHE), dopamine (DOPA), 5-hydroxytryptamine (5-HT), or endothelin-1 (ET-1) produced a dose-dependent reduction in pulpal blood flow (order of potency: ET-1>A=NA>PHE=DOPA=5-HT); acetylcholine induced a dose-dependent increase in pulpal blood flow; histamine, isoproterenol and adenosine produced no significant changes. In isolated arteriole preparations, intraluminal delivery of A, NA, PHE, DOPA or 5-HT produced dose-dependent vasoconstriction (A=NA>PHE=DOPA=5-HT). Acetylcholine relaxed NA-precontracted vessels dose-dependently. Histamine and isoproterenol produced a small vasodilatation. Intraluminal ET-1 produced a small vasoconstriction at 10(-8)M, whereas extraluminal ET-1 produced a dose-dependent vasoconstriction from 10(-10)M and above. Intraluminal adenosine failed to dilate vessels precontracted with ET-1, whereas extraluminal adenosine caused a complete relaxation. These combined in vivo and in vitro data suggest that, in the rat incisor, the pulpal microcirculation is capable of functional regulation and that pulpal blood flow may be modulated by endothelium-related factors, metabolic (tissue-related) factors, as well as humoral (blood-borne) factors.     

Biphasic pulp blood-flow response to substance P in the dog as measured with a radiolabelled, microsphere injection method

A dose of the vasoactive substance P (SP), affecting local circulation only (0.0001-0.001 micrograms/kg body weight) when given by a close injection into the maxillary artery, caused a biphasic flow response in pulpal blood flow (PBF), as measured by a radioisotope-labelled 15 micron microsphere injection technique. Immediately after the SP injection, PBF increased some 66 per cent (p less than 0.02) and vascular hindrance (Z) decreased to 40 per cent against control values (p less than 0.02), indicating vasodilation. Thirty seconds after the SP injection, PBF decreased by 53 per cent (p less than 0.05), and pulpal Z increased 139 per cent against control values (p less than 0.02), indicating decreased blood flow. This biphasic flow response may be due to the active vasodilation of arterioles by SP, which causes a compression of venules and hence a reduction of PBF in what is a low-compliance system.