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PubMedDate not supplied

Tranilast reduces mesenteric vascular collagen deposition and chymase-positive mast cells in experimental diabetes.

The mast cell has a central role in the pathogenesis of fibrosis a common feature of diabetic microvascular complications. Increased mast cell numbers have been demonstrated in diabetic nephropathy in association with renal fibrosis, and diabetes acutely increases mast cell infiltration in the mesentery. Antimast cell agents such as tranilast may ameliorate the acute vascular changes in diabetes due to stabilisation of mast cells and/or reduction in mast cell numbers. After 3 weeks of streptozotocin diabetes, light microscopy techniques were used to estimate mesenteric vessel fibrosis and mast cell infiltration. Mast cells were identified by toluidine blue staining and tryptase, chymase and TGF-beta immunohistochemistry in three study groups of rats: control, diabetic and plus tranilast. Diabetes was associated with an increase in both mesenteric vessel fibrosis and mast cell numbers. Administration of tranilast to diabetic rats reduced mesenteric vessel fibrosis and this was associated with a reduction in chymase-positive mast cells. These changes were independent of mast cell TGF-beta and were not associated with a reduction in tryptase-positive mast cells. The amelioration of diabetes-induced vessel fibrosis may be due to a reduction in the liberation of angiotensin II by inhibiting mast cell chymase.

Animals↗
PubMed1988

Agonist-induced activation of rat mesenteric resistance vessels: comparison between noradrenaline and vasopressin.

The effects of noradrenaline (NA, 10(-5) M) and [arginine8]vasopressin (AVP, 10(-7) M) on tension in Ca2+-free medium and on membrane potential, and the inhibition of NA- and AVP-induced contractions by isradipine, have been compared in mesenteric resistance vessels (MRVs) from Wistar-Kyoto (WKY) rats. The release of intracellular Ca2+ by AVP contributed significantly less to its tension development than does that by NA. Nonetheless, the concentration-response curves for inhibition by isradipine of NA- and AVP-induced tonic tension were nearly identical. Similarly, these two agonists produced the same degree of membrane depolarization. In addition, both agonists were able to stimulate large contractions in vessels previously depolarized by 80 mM K+. AVP also stimulated 45Ca influx into rat cultured aortic smooth muscle cells. In contrast to the stimulation of 45Ca influx by KCl depolarization, the agonist-stimulated 45Ca influx was insensitive to inhibition by organic Ca2+ antagonists. It is concluded that Ca2+ entry through receptor-operated Ca2+-permeable channels (ROCs) may contribute to agonist-induced activation of rat aortic and MRV smooth muscle.

Animals↗
PubMedDate not supplied

Evaluation of bowel and mesenteric blunt trauma with multidetector CT.

Bowel and mesenteric injuries are detected in 5% of blunt abdominal trauma patients at laparotomy. Computed tomography (CT) has been shown to be accurate for the diagnosis of bowel and mesenteric injuries and is the diagnostic test of choice in the evaluation of blunt abdominal trauma in hemodynamically stable patients. Specific CT findings of bowel and mesenteric injuries include bowel wall defect, intraperitoneal and mesenteric air, intraperitoneal extraluminal contrast material, extravasation of contrast material from mesenteric vessels, and evidence of bowel infarct. Specific signs of mesenteric injury are vascular beading and abrupt termination of mesenteric vessels. Less specific signs of bowel and mesenteric injuries include focal bowel wall thickening, mesenteric fat stranding with focal fluid and hematoma, and intraperitoneal or retroperitoneal fluid. When only nonspecific signs of bowel and mesenteric injuries are seen on CT images, correlation of CT features with clinical findings is necessary. A repeat CT examination after 6-8 hours if the patient's condition is stable may help determine the significance of these nonspecific findings.

Abdominal Injuries↗
PubMed2006

Substituted adamantyl-urea inhibitors of the soluble epoxide hydrolase dilate mesenteric resistance vessels.

The epoxyeicosatrienoic acids (EETs) have been identified as endothelium-derived hyperpolarizing factors. Metabolism of the EETs to the dihydroxyeicosatrienoic acids is catalyzed by soluble epoxide hydrolase (sEH). Administration of urea-based sEH inhibitors provides protection from hypertension-induced renal injury at least in part by lowering blood pressure. Here, we investigated the hypothesis that a mechanism by which sEH inhibitors elicit their cardiovascular protective effects is via their action on the vasculature. Mesenteric resistance arteries were isolated from Sprague-Dawley rats, pressurized, and constricted with the thromboxane A2 agonist U46619 (9,11-dideoxy-11,9-epoxymethano-prostaglandin F2alpha). Mesenteric arteries were then incubated with increasing concentrations of the sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA). AUDA resulted in a concentration-dependent relaxation of mesenteric arteries, with 10 microM resulting in a 48 +/- 7% relaxation. Chain-shortened analogs of AUDA had an attenuated vasodilatory response. Interestingly, at 10 microM, the sEH inhibitors 1-cyclohexyl-3-dodecylurea, 12-(3-cyclohexylureido)dodecanoic acid, and 950 [adamantan-1-yl-3-{5-[2-(2-ethoxyethoxy)ethoxy]pentyl}urea] were significantly less active, resulting in a 25 +/- 8%, 10 +/- 9%, and -8 +/- 3% relaxation, respectively. Treatment of mesenteric arteries with tetraethylammonium, iberiotoxin, ouabain, or glibenclamide did not alter AUDA-induced relaxation. The AUDA-induced relaxation was completely inhibited when constricted with KCl. In separate experiments, denuding mesenteric resistance vessels did not alter AUDA-induced relaxation. Taken together, these data demonstrate that adamantyl-urea inhibitors have unique dilator actions on vascular smooth muscle compared with other sEH inhibitors and that these dilator actions depend on the adamantyl group and carbon chain length.

Adamantane↗
PubMed1993

Contractile responses and signal transduction of endothelin-1 in aorta and mesenteric vasculature of adult spontaneously hypertensive rats.

The contractile responses and generation of intracellular second messengers in response to endothelin-1 (ET-1), a potent vasoconstrictor peptide released locally by endothelial cells and involved in the regulation of vascular tone, were investigated in different segments of the vascular tree of adult 18-week-old spontaneously hypertensive rats (SHR) as compared with age-matched Wistar-Kyoto (WKY) rats. Aorta rings of SHR showed lower maximum response to ET-1 in comparison with WKY rats. Rings of the main superior mesenteric artery of SHR and WKY showed similar responses to ET-1. Small mesenteric resistance arteries of SHR, mounted on a wire myograph, developed similar tension to those of WKY rats in response to ET-1. The dose-response of inositol phosphates to ET-1 was significantly blunted in thoracic aorta of SHR compared with WKY rats, whereas it was similar in the mesenteric arterial bed. Baseline 1,2-diacylglycerol content was higher in thoracic aorta of SHR than WKY, while it was similar in the mesenteric arterial bed of the two strains. The response of 1,2-diacylglycerol to ET-1 was blunted in aorta of SHR, whereas no significant differences in diacylglycerol accumulation could be found in mesenteric vessels between SHR and WKY. In small mesenteric arteries, the dose-response to ET-1 of cytosolic free calcium, measured with the fluorescent dye Fura 2-AM, was similar in the two groups of rats. We conclude that in the aorta of 18-week-old SHR there is reduced generation of second messengers (inositol phosphates and diacylglycerol), which underlies its decreased response to ET-1. In mesenteric vessels (both proximal and distal) signal transduction is similar in SHR and WKY, and as a result contractile responses in both species are comparable. The responses to ET-1 of the arterial tree in terms of contractility and second messenger generation may reflect the adaptive processes taking place as a consequence of elevated blood pressure within the arterial wall of different segments of the vasculature of SHR.

Animals↗
PubMed1991

Mesenteric vascular anatomy at CT: normal and abnormal appearances.

The appearance of the mesenteric vessels on computed tomographic scans was evaluated in 187 patients to determine the variations in the anatomic relationships between the mesenteric vessels in normal patients, in patients with malrotation, and in patients with abdominal masses. In 166 patients (88.8%), a portion of the cranial segment of the superior mesenteric vein (SMV) was anterior and to the right of the superior mesenteric artery (SMA), although other normal configurations also occurred. A portion of the cranial segment of the SMV was directly anterior to the SMA in 15 patients (8.0%) and directly to the right of the SMA in 16 patients (8.6%). Of eight patients with complete inversion of the SMA and SMV, one had normal midgut rotation, two had malrotation, and six had neoplasms that displaced the vessels (one of these six also had malrotation). Of eight patients with inversion of only a part of the mesenteric vessels, none had malrotation. Although mesenteric inversion should stimulate a careful evaluation for malrotation, it is not pathognomonic of this condition.

Adolescent↗
PubMed1979

Effect of age on noradrenaline sensitivity of mesenteric resistance vessels in spontaneously hypertensive and Wistar-Kyoto rats.

1. We have compared the noradrenaline sensitivity of 150 micron arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar-Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks. 2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 mu mol/l). 3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats. 4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.

Aging↗
PubMedDate not supplied

Intestinal malrotation as an incidental finding on CT in adults.

BACKGROUND: Intestinal malrotation in adults is usually an incidental finding on computed tomography (CT). We present the CT findings of 18 adult patients with malrotation and discuss the clinical implications. METHODS: Abdominal scans of 18 patients (12 women, six men; age range = 15-79 years) with intestinal malrotation were reviewed. Special attention was directed to the location of the superior mesenteric vessels, the location of the small and large bowels, the size of the uncinate process, the situs definition, and additional anomalies. RESULTS: The malrotation was an incidental finding in all but one patient. The malrotation was type Ia in 17 patients and IIc in the one symptomatic patient. The superior mesenteric vessels were vertically oriented in 10, inverted in two, normally positioned in four, and mirror imaged in two cases with situs ambiguus. All patients had aplasia of the pancreatic uncinate process, five had a short pancreas, and two had a preduodenal portal vein. Fourteen patients had a normal situs and four had heterotaxia. Seven patients had polysplenia, six of which with associated inferior vena cava anomalies. CONCLUSIONS: Intestinal malrotation can be diagnosed on CT by the anatomic location of a right-sided small bowel, left-sided colon, an abnormal relationship of the superior mesenteric vessels, and aplasia of the uncinate process. Awareness of these abnormalities is necessary to diagnose this anomaly. It should be sought in patients with a situs problem, inferior vena cava anomalies, polysplenia, or preduodenal portal vein. Although usually an incidental finding, it is important to diagnose such a malrotation because it may cause abdominal symptoms. Also, knowledge of associated vascular anomalies is important when abdominal surgery is planned.

Adolescent↗
PubMed1994

Mediation of excitatory neurotransmission by the release of ATP and noradrenaline in sheep mesenteric lymphatic vessels.

1. Spontaneous isometric contractions were measured in rings of sheep mesenteric lymphatics. Field stimulation at short pulse widths increased the frequency of spontaneous contractions and this response was blocked by 3 x 10(-7) M omega-conotoxin and by 10(-6) M guanethidine. 2. Rings that had been incubated with [3H]noradrenaline release 3H in response to field stimulation in a frequency-dependent manner. 3. Exogenous ATP mimicked the response to field stimulation and this was blocked by 10(-4) M suramin but not by prior desensitization with 10(-6) M alpha, beta-methylene ATP. Exogenous noradrenaline was not blocked by 10(-4) M suramin. 4. The excitatory response to field stimulation was not blocked by 10(-4) M suramin but a combination of 10(-4) M suramin and 3 x 10(-6) M phentolamine did block the response. 5. In rings taken from sheep that had been pretreated with reserpine, 10(-4) M suramin alone blocked the response to field stimulation. 6. The results of this study suggest that the excitatory response to stimulation of intramural nerves in sheep mesenteric lymphatics is mediated by the release of both ATP and noradrenaline.

Adenosine Triphosphate↗
PubMed1990

Effects of atrial natriuretic peptide on isolated bovine mesenteric lymph vessels.

The mode of action of atrial natriuretic peptide (ANP) on bovine mesenteric lymphatics was investigated by recording isometric tensions in isolated cylindrical segments. ANP in concentrations from 5 to 30 ng/ml caused dose-related decreases in the rhythm and amplitude of spontaneous contractions. No tachyphylaxis was observed in the ANP-induced responses in lymph vessels. Addition of ANP in a low concentration ranging from 3 to 100 ng/ml produced a dose-dependent relaxation in the lymphatic preparations precontracted by 10(-7) M bradykinin. The ANP-induced relaxation was not modified by pretreatment with 5 x 10(-7) M propranolol, 5 x 10(-7) M atropine, 10(-6) M cimetidine, 5 x 10(-5) M aspirin, or 10(-5) M ouabain. The mechanical rubbing of endothelial cells in the lymph vessels caused no significant effect on the ANP-induced relaxation. The relaxation, however, was significantly reduced by pretreatment with 10(-5) M methylene blue. These results suggest that ANP in a low concentration seems to inhibit lymph transport through a reduction of spontaneous contractions and a marked relaxation of lymphatic smooth muscles in bovine mesenteric lymphatics and that ANP may produce the relaxation through synthesis of guanosine 3',5' cyclic monophosphate, independent of the lymphatic endothelium.

Animals↗
PubMed1993

Allopurinol protects the bowel from necrosis caused by indomethacin and temporary intestinal ischemia in mice.

The present study was undertaken to evaluate if allopurinol administration protects mice from bowel necrosis caused by temporary intestinal ischemia followed by indomethacin (INDO). We have previously reported that ischemia (15-minute occlusion of superior mesenteric vessels) followed by intravenous (i.v.) INDO caused significant bowel necrosis in CD-1 mice. Ischemia or INDO alone did not cause necrosis. To investigate protective measures against necrosis, we used CD-1 mice, 25 to 30 g. Forty-four animals were gavage fed 1 mL of water for 7 days and 32 animals were gavage fed 10 mg/kg allopurinol for 7 days. On the seventh day all animals were anesthetized and the superior mesenteric vessels occluded for 15 to 20 minutes, followed by i.v. INDO (0.5 mg/kg) once daily for 3 days. Animals who died were examined for bowel necrosis and all animals were killed 7 days after surgery and necropsied. Of the 44 saline-fed animals, 12 developed bowel necrosis (27%). Of the 32 allopurinol-fed animals, 1 developed necrosis (3%). The result of Fisher's exact two-tailed test was P = .006. Pretreatment with oral allopurinol significantly protects the mice from developing bowel necrosis when the mesenteric vessels are temporarily occluded and INDO is administered. Allopurinol may prevent reperfusion injury by inhibiting formation of xanthine oxidase generated, oxygen-derived free radicals and may be valuable in pretreating premature infants with patent ductus arteriosus who have had an ischemic episode in whom INDO use is contemplated.

Allopurinol↗
PubMedDate not supplied

Effect of no touch isolation on survival and recurrence in curative resections for colorectal cancer.

BACKGROUND: Curative resections for colorectal cancer were studied to determine the effects of the application of bowel ligatures and the sequence of mesenteric ligation on survival and recurrence as part of the no touch isolation technique. METHODS: Records documenting the application of bowel ligatures in 2015 consecutive curative resections for colorectal cancer and the sequence of mesenteric vessel ligation in 1863 of these cases were reviewed. RESULTS: Bowel ligatures applied before tumor mobilization in curative resections for colorectal cancer consistently reduced cancer-related deaths and the incidence of distant, local, and suture line recurrences. Their impact on survival began to approach statistical significance in Dukes C colon cancers and in the overall group of colon cancers (P = .019). Early application of bowel ligatures decreased the incidence of subsequent liver metastases from 15.3% to 9.5% and systemic metastases from 18.0% to 13.0% (P <.0001). Local recurrence was reduced from 18.3% to 10.8% in Dukes B and from 28.6% to 19.3% in Dukes C cases (P = .002). The incidence of suture line recurrence was reduced from 6.8% to 0.9% in Dukes B and from 12.2% to 3.2% in Dukes C cases (P = .001). Ligating the mesenteric vessels before mobilizing the tumor did not significantly affect survival, but did increase the incidence of distant systemic metastases and of local and suture line recurrences. With early vessel ligation, systemic metastases developed in 24.5% of 813 curative resections, compared to 15.7% of 1050 cases in which vessel ligation followed tumor mobilization (P <.001). Early vessel ligation in Dukes C cancers was associated with an increase in local recurrence from 22.5% to 34.2% and in suture line recurrence from 6.9% to 18.8% (P = .0003). The correlation became greater as the stage of the cancer became more advanced. CONCLUSION: By controlling lymphatic and intraluminal dissemination of malignant cells as well as minimizing tumor manipulation, bowel ligatures help to reduce cancer-related deaths and the incidence of distant, local, and suture line recurrences. The sequence in which the mesenteric vessels were ligated did not affect survival, but did change the distribution of distant metastases and the incidence of local and suture line recurrences.

Colon↗
PubMed1993

Alterations in cytosolic calcium-binding proteins that increase felodipine fluorescence in spontaneously hypertensive rats.

OBJECTIVE: To clarify the role of calcium-binding proteins (CaBP) in hypertension. DESIGN: CaBP from several organs of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were purified and their characteristics compared between the two strains. The CaBP were purified by applying the soluble cytosolic fractions from mesenteric vessels, heart, kidney and brain of 4- and 10-week-old SHR and WKY rats to a phenyl-Sepharose column. Felodipine binding to the purified CaBP was then measured. RESULTS: The fluorescence intensity of felodipine increased in a calcium-dependent manner when it bound to CaBP. The pK 0.5 Ca2+ values derived from the calcium ion-felodipine fluorescence curves for each CaBP preparation from organs of the two strains were similar, indicating that the calcium sensitivities of the CaBP to the felodipine binding process are similar in SHR and WKY rats. In 10-week-old SHR the mean levels of felodipine-bound CaBP in heart, brain and kidney were significantly altered compared with those in WKY rats. No such alterations were observed in heart, kidney and brain from 4-week-old SHR and WKY rats. Conversely, the mean levels of felodipine-bound CaBP in mesenteric vessels from 4- and 10-week-old SHR were reduced significantly compared with those of age-matched WKY rats. CONCLUSIONS: These results suggest that the levels of cytosolic felodipine-bound CaBP from heart, kidney and brain are altered in response to elevated blood pressure, and that reduced levels of felodipine-bound CaBP in the mesenteric vessels of SHR might be a primary characteristic of this rat strain.

Animals↗
PubMed1995

[Primary solid tumors of the mesentery].

The interest for the primary solid tumors of the mesentery (TSPM) is justified by the difficulties of preoperative diagnosis and surgical treatment of these unusual lesions. We analyzed 68 TSPM operated in the Department of General Surgery of Fundeni Hospital between 1960-1993. In the study were included only the lymphoma presented as mesenteric masses (n = 17); the enlarged mesenteric lymph nodes were excluded. The most common malignant tumor was the fibroma (n = 8) and lipoma (n = 10). In the resection of mesenteric tumors exposure of the superior mesenteric vessels is important. The relation between tumoral and superior mesenteric vessels is the necessary criterion of resectability: in 41 cases from 43 unresectable lesions the reason of unresectability was the invasion of the superior mesenteric vein and artery; in only two cases the reason was the presence of liver metastases. The resectability was not influenced by the multiplicity of the lesions: in all cases with multiple mesenteric tumors (6 patients) the resection was performed. The distant metastases of TSPM are rare; on the contrary, the local invasion is common.

Adult↗
PubMed1995

Monoamine oxidase activity in the uterine and mesenteric arteries, vessels of ovarian pedicle and myometrium of pigs during the oestrous cycle.

Activities of total monoamine oxidase (MAO-T) and of both subtypes: MAO-A and MAO-B were examined in the uterine artery, vessels of ovarian pedicle (subovarian veno-arterial network), mesenteric artery and myometrium on the 0-2nd, 13-14th and 16-18th days of the oestrous cycle of pigs. It was found that in the uterine artery MAO-T, MAO-A and MAO-B activities were the highest on the 0-2nd days (100%); on day 13-14 they were lower by 85.4, 84.8 and 87.4% (p < 0.01), respectively, and on days 16-18 they were lower by 52.4, 57.5 and by 54.1% (p < 0.01) in comparison with the value on the 0-2nd days of ovarian cycle. The activities of MAO-T, MAO-A and MAO-B in the vessels of ovarian pedicle on the 0-2nd days were the lowest, whereas on days 13-14 they were the highest (p < 0.01), MAO-T by 445.3%, MAO-A by 315.6%, MAO-B by 344.7%, and they were higher on days 16-18 by 133.8% (p < 0.01), 85.9 (p < 0.05) and by 281.5% (p < 0.01) in comparison with the value on the 0-2nd day of ovarian cycle, respectively. The activities of examined enzymes in mesenteric artery were higher on 0-2nd and 16-18th days, whereas MAO-T and MAO-B they were lower by 39.0% and MAO-A by 22.3% (p < 0.05) on 13-14th days of oestrous cycle. In myometrium the activities of MAO-T, MAO-A and MAO-B on the 0-2nd days (100%) were the lowest, whereas on days 13-14 the activities were the highest (p < 0.01), MAO-T by 326.3%, MAO-A by 363.3% and MAO-B by 364.1%, and on days 16-18 the MAO-T and MAO-B activities were also higher by 99.4% and 150.7% (p < 0.01) respectively, whereas MAO-A activity was similar to the value on the 0-2nd days. The high MAO activity in the vessels of pig ovarian pedicle may be a significant factor in the ovarian vasotone decrease and increase in the ovarian blood flow during the luteal phase of ovarian cycle.

Analysis of Variance↗
PubMed1999

A novel inhibitor of advanced glycation end-product formation inhibits mesenteric vascular hypertrophy in experimental diabetes.

AIMS/HYPOTHESIS: Previous studies in our laboratory have shown that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature and that this process can be attenuated by the inhibition of advanced glycation with aminoguanidine. Since aminoguanidine can also act as an inhibitor of nitric oxide synthase, the effect of a novel inhibitor of advanced glycation end-products, formation that does not inhibit nitric oxide synthase, known as 2,3 diaminophenazine (2,3 DAP) was evaluated. METHODS: Initially, in vitro assessment of the ability of 2,3 diaminophenazine to inhibit formation of advanced glycation products was performed. Subsequently, in vivo studies evaluating 2,3 diaminophenazine and aminoguanidine were carried out. Animals were followed for 3 weeks after induction of diabetes and randomised to no treatment, aminoguanidine or 2,3 diaminophenazine. Mesenteric vessels were weighed and advanced glycation end-products were measured by radioimmunoassay in vessel and kidney homogenates. In addition, these products were assessed in mesenteric vessels by immunohistochemistry. RESULTS: When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight. Treatment of diabetic rats with aminoguanidine or 2,3 diaminophenazine resulted in attenuation of vascular hypertrophy. Both aminoguanidine and 2,3 diaminophenazine reduced the formation of advanced glycation end-products as measured by radioimmunoassay and as assessed immunohistochemically in these vessels. This reduction was also observed in the kidney. CONCLUSION/INTERPRETATION: These data support the concept that the effects of aminoguanidine in reducing diabetes associated vascular hypertrophy are via inhibition of advanced glycation end-products dependent pathways.

Animals↗
PubMed1990

Adrenergic modulation of calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation in the rat mesenteric resistance vessel.

Pharmacological studies showed that periarterial nerve stimulation (PNS) of the perfused rat mesenteric vascular bed contracted with endothelin, a vasoconstrictor peptide, in the presence of prazosin (alpha 1-adrenoceptor antagonist) produced a frequency-dependent neurogenic vasodilation when the adrenergic neurotransmission was blocked by the adrenergic neuron blocker, guanethidine. The PNS-evoked vasodilation was attenuated by tetrodotoxin and capsaicin treatment, and was also inhibited when the adrenergic neurotransmitter (norepinephrine; NE) release was left intact in the absence of guanethidine. However, in the combined presence of an alpha 2-adrenoceptor antagonist (yohimbine) and prazosin, PNS caused a marked neurogenic vasodilation even when the neuronal release of NE was left intact. These results suggest that NE released from adrenergic nerves regulates the release of a vasodilator substance, CGRP, through activation of alpha 2-adrenoceptors on CGRP-containing vasodilator nerves.

Adrenergic Fibers↗