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This study proposed and tested the cross-sectional effects of patient-centered communication (PCC) on cancer screening behaviors via an affective-cognitive sequential chain of mediation through cancer worry and health self-efficacy. Cross-sectional data were analyzed from four iterations of the Health Information National Trends Survey (2011, 2014, 2017, and 2020). The results found that lowered cancer worry following PCC does not show a cross-sectional positive effect in promoting cancer screening behaviors, while enhanced health self-efficacy as a subsequent state is a facilitator of screening behaviors. The findings further demonstrated increased PCC, a rise in cancer worry, and a sustained level of health self-efficacy. Also, our research has identified an upward trend in cancer screening behaviors from 2011 to 2017, followed by a notable decrease in 2020. These insights underscore the nuanced ways PCC can foster cancer screening behaviors, emphasizing the importance of emotional and cognitive aspects in clinical settings., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Familial hypercholesterolemia (FH) is a genetic disorder affecting the metabolism of lipoprotein, characterized by elevated levels of plasma concentrations of low-density lipoprotein cholesterol (LDLC). The most common FH cause is mutations within the gene that encodes for the LDL receptor (LDLR) protein. Two induced pluripotent stem cell (iPSC) lines were generated from patients with FH, each carrying a single heterozygous mutation in the LDLR gene, one is a missense mutation, c.631C > T, and the other is a splice-site mutation, c.313 + 1G > A. Both iPSC lines exhibited strong expression of pluripotency markers, demonstrated the ability to differentiate into derivatives of the three germ layers, and maintained normal karyotypes. These derived iPSC lines represent powerful tools for in vitro modeling FH and offer a promising platform for therapeutic development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JCW is a co-founder and scientific advisory board member of Greenstone Biosciences. The other authors affirm that they do not possess any known competing financial interests or personal relationships that could have influenced the work presented in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Specific mutations in the TTR gene are responsible for the development of variant (hereditary) ATTR amyloidosis. Here, we generated two human induced pluripotent stem cell (iPSC) lines from patients diagnosed with Transthyretin Cardiac Amyloidosis (ATTR-CM) carrying heterozygous mutation in the TTR gene (i.e., p.Val30Met). The patient-derived iPSC lines showed expression of high levels of pluripotency markers, trilineage differentiation capacity, and normal karyotype. The generation of these iPSC lines represents a great tool for modeling patient-specific amyloidosis in vitro, allowing the investigation of the pathological mechanisms related to the disease in different cell types and tissues., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph C. Wu reports a relationship with Greenstone Biosciences that includes: co-founder & board member., (Copyright © 2023. Published by Elsevier B.V.)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a congenital arrhythmic syndrome caused by the RYR2 gene encoded ryanodine receptor. Mutations on RYR2 are commonly associated with ventricular tachycardia after adrenergic stimulation, leading to lethal arrhythmias and sudden cardiac death. We generated two human induced pluripotent stem cell (iPSC) lines from CPVT affected patients carrying single missense heterozygote RYR2 mutations, c.1082 G > A and c.100 A > C. Pluripotency and differentiation capability into derivatives of three germ layers were evaluated along with karyotype stability in the report. The generated patient-specific iPSC lines provide a reliable tool to investigate the CPVT phenotype and understand underlaying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Dilated cardiomyopathy (DCM) is a progressive heart muscle disease that can culminate with heart failure and death. Mutations in several genes can cause DCM, including hyperpolarization-activated cyclic nucleotide-gated channel (HCN4), which has a critical function in the autonomic control of the heart rate. Here, we generated two human induced pluripotent stem cell (iPSC) lines generated from two DCM patients carrying variants in the HCN4 gene (c.2587G > T and c.2846G > A). Both lines display normal karyotype, typical morphology of pluripotent stem cells, and differentiate into all three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of DCM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Induced pluripotent stem cells (iPSCs) have become widely adopted tools in cardiovascular biology due to their ability to differentiate into patient-specific cell types. Here, we describe the current protocols, important discoveries, and experimental limitations from the iPSC-derived cell types of the human heart: cardiomyocytes, cardiac fibroblasts, vascular smooth muscle cells, endothelial cells, and pericytes. In addition, we also examine the progress of 3D-based cell culture systems., Recent Findings: There has been rapid advancement in methods to generate cardiac iPSC-derived cell types. These advancements have led to improved cardiovascular disease modeling, elucidation of interactions among different cell types, and the creation of 3D-based cell culture systems able to provide more physiologically relevant insights into cardiovascular diseases. iPSCs have become an instrumental model system in the toolbox of cardiovascular biologists. Ongoing research continues to advance the use of iPSCs in (1) disease modeling, (2) drug screening, and (3) clinical trials in a dish., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The NF-κB pathway and chemokine (C-C motif) ligand 5 (CCL5) are involved in pain modulation; however, the precise mechanisms of their interactions in chronic neuropathic pain have yet to be established., Methods: The present study examined the roles of spinal NF-κB and CCL5 in a neuropathic pain model after chronic constriction injury (CCI) surgery. CCI-induced pain facilitation was evaluated using the Plantar and von Frey tests. The changes in NF-κB and CCL5 expression were analyzed by immunohistochemistry and Western blot analyses., Results: Spinal NF-κB and CCL5 expression increased after CCI surgery. Repeated intrathecal infusions of pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor) decreased CCL5 expression, inhibited the activation of microglia and astrocytes, and attenuated CCI-induced allodynia and hyperalgesia. Intrathecal injection of a CCL5-neutralizing antibody attenuated CCI-induced pain facilitation and also suppressed spinal glial cell activation after CCI surgery. However, the CCL5-neutralizing antibody did not affect NF-κB expression. Furthermore, selective glial inhibitors, minocycline and fluorocitrate, attenuated the hyperalgesia induced by intrathecal CCL5., Conclusions: The inhibition of spinal CCL5 expression may provide a new method to prevent and treat nerve injury-induced neuropathic pain.

The present study examined the effects of intrathecal use of resveratrol on pain hypersensitivities, spinal glia activation, and CX3CR1 expression in the model of bone cancer pain (BCP). The BCP model was established through intrathecally injecting Walker 256 mammary gland carcinoma cells to Sprague-Dawley rats. We found that spinal CX3CR1 expression and glial activation aggravated after inoculation. Resveratrol (i.t.) attenuated bone cancer-induced pain hypersensitivities, decreased CX3CR1 expression and glial activation in the spine in a BCP model. Resveratrol (i.t.) also attenuated mechanical allodynia resulting from intrathecally injecting fractalkine in rats. Inhibition of spinal glial activation and CX3CR1 upregulation may involve in resveratrol's analgesic effects. These findings demonstrated that resveratrol attenuated pain facilitation through inhibiting spinal glial activation and CX3CR1 upregulation in a BCP model., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

The present study was aimed to investigate the effect of pretreatment with Danshensu (DSS) on rat aortic endothelial cells (RAECs) senescence and the underlying mechanisms. Cultured RAECs at fourth and twelfth passages were taken as young and old groups, respectively. DSS and DSS+nicotinamide (DSS+N) groups were incubated with DSS and DSS in combination with nicotinamide, an inhibitor of silent information regulator 1 (SIRT1), from the fourth to twelfth passage, respectively. The cell status of senescence was determined by the senescence-associated β-galactosidase (SA β-gal) staining, and 4,6-diamino-2-phenyl indole (DAPI) fluorescent dye was used to detect senescence associated heterochromatin foci (SAHF) formation; Thiobarbituric acid (TBA) and colorimetric methods were used to evaluate malondialdehyde (MDA) and H₂O₂contents; Western blot was employed to analysis the expressions of xanthine oxidase (XOD), SIRT1 and superoxide dismutase 2 (SOD₂) in the RAECs. The results showed that, in comparison with young group, the old group exhibited higher SA β-gal positive and SAHF formation rates, as well as higher MDA and H₂O₂levels (P < 0.05 or P < 0.01), whereas DSS pretreatment reduced SA β-gal positive and SAHF formation rates, decreased MDA and H2O2 contents (P < 0.05 or P < 0.01). The protection of DSS was reversed by nicotinamide. Compared with the young group, the old group showed higher expression levels of XOD, but lower SIRT1 and SOD₂expression levels (P < 0.05 or P < 0.01). With the pretreatment of DSS, the expression of XOD was declined, and the expression levels of SIRT1 and SOD₂were elevated, while nicotinamide reversed the effects of DSS. These results suggest that DSS delays senescence of RAECs via up-regulation of SIRT1.

The present study was aimed to observe the protective effect of exogenous hydrogen sulfide (H₂S) on vascular structural and functional changes of aorta in D-galactose-induced subacute aging rats. Adult male SD rats were randomly divided to five groups: the vehicle group, the D-galactose (D-gal) group, and the three NaHS groups treated with low (1 μmol·kg⁻¹·d⁻¹), middle (10 μmol·kg⁻¹·d⁻¹) or high (100 μmol·kg⁻¹·d⁻¹) dose of NaHS respectively. The D-gal group rats were given subcutaneously injection of 125 mg/kg D-gal per day for eight weeks to induce subacute aging model. In the NaHS group, D-gal was administered as above but with NaHS intraperitoneally injected at a dosage of 1, 10, 100 μmol·kg⁻¹·d⁻¹ respectively. Equivalent volumes of saline were administered per day for eight weeks in vehicle group. Morphological changes of aorta were observed by HE and Masson staining. The level of H₂S in serum, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), as well as anti-superoxide anions in vascular tissue were determined by spectrophotometry. Angiotensin II (AngII) levels in plasma were measured using competitive enzyme immunoassay. The expression of angiotensin II type 1 receptor (AT1R) in aorta was determined by Western blot. The results showed that the aging aortic morphologic changes in model rats were ameliorated in NaHS groups. Decreased vascular endothelial exfoliative cells and vascular smooth muscle cell (SMC) proliferation were shown in NaHS groups by HE staining. Masson staining analysis showed reduced relative contents of collagen fibers (P < 0.05) and SMC (P < 0.05) in NaHS groups. Compared to vehicle group, serum concentration of H₂S in D-gal group was decreased, while it was increased in NaHS groups after treatment with NaHS (P < 0.05). In the D-gal group, the concentration of AngII in plasma was significantly increased compared with that in vehicle group, while it was decreased in NaHS groups (P < 0.05). Moreover, levels of vascular tissue anti-superoxide anion and the activity of SOD were obviously higher, MDA was significantly lower in all NaHS treated groups than those in the D-gal group respectively (P < 0.05). Western blot analysis showed that the expression of AT1R was increased in D-gal group compared with that in vehicle group, while it was decreased after treatment with NaHS compared with that in D-gal group (P < 0.05). These results suggest that exogenous H₂S can ameliorate the age-related changes of aortic morphology, decrease the concentration of AngII in plasma, down-regulate the expression of AT1R in vascular tissue, and mitigate the level of oxidative stress. These changes delay the vascular aging in aging rats ultimately.

Aim: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process., Methods: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits., Results: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H₂O₂ in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group., Conclusion: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.

Background: Little research has been conducted regarding the implications of Sirt1 (a classic III HDAC) in neuropathic pain. The aim of this study was to investigate the variation in the expressions of spinal Sirt1 and acetyl-histone H3 in a rat model of chronic constriction injury., Methods: A neuropathic pain model of chronic constriction injury (CCI) was established in a unilateral hind limb in Sprague-Dawley rats., Results: Western blot analysis and immunohistochemistry revealed that Sirt1 (silent information regulator) expression decreased, whereas acetyl-histone H3 increased in the spinal cord following CCI surgery. The intrathecal administration of resveratrol, an activator of Sirt1, attenuated CCI-induced mechanical allodynia and thermal hyperalgesia, increased Sirt1 expression, and decreased acetyl-histone H3 in the spine. Resveratrol induced no obvious histopathological changes in the spinal cord., Conclusions: Our data provide new evidence for the contribution of spinal Sirt1 to the initiation and maintenance of neuropathic pain. The antinociceptive effects of resveratrol may be mediated through the activation of spinal Sirt1 in CCI rats.

The present study was aimed to investigate the effect of pretreatment with hydrogen sulfide (H2S) on human umbilical vein endothelial cells (HUVECs) senescence and the underlying mechanism. Cultured HUVECs at twelfth and fourth passages were taken as old and young groups, respectively. Sodium hydrosulfide (NaHS, donor of H2S) group was treated with NaHS from fourth to twelfth passage. The cell senescence was determined by senescence-associated β-galactosidase (SA β-gal) staining. DAPI fluorescent dye was used to detect cellular apoptosis. Western blot was used to analyze the expression levels of xanthine oxidase (XOD), manganese-superoxide dismutase (Mn-SOD) and the subunits p67(phox) of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the HUVECs. Colorimetric method was used to detect SOD activity and cellular hydrogen peroxide (H2O2) level. The results showed that, compared with young group, the old group exhibited higher SA β-gal positive rate and cellular apoptosis, while NaHS pretreatment decreased SA β-gal positive rate and cellular apoptosis. Compared with the young group, the old group showed increased expression levels of XOD and p67(phox), as well as lower Mn-SOD expression level. With the pretreatment of NaHS, the up-regulations of XOD and p67(phox) levels and down-regulation of Mn-SOD level were inhibited. Compared with the young group, the old group showed lower SOD activity and higher H2O2 level, whereas NaHS pretreatment reversed the changes of SOD activity and H2O2 level. These results suggest that H2S delays senescence of HUVECs through lessening oxidative stress.

The present study aimed to investigate the protective effect and mechanism of hydrogen sulfide donor NaHS administration against gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) in rats. GI-R injury was induced by clamping the celiac artery of adult male SD rats for 30 min and followed by reperfusion for 1 h. The rats were randomly divided into sham group, GI-R group, NaHS group, glibenclamide group and pinacidil group. Gastric mucosal damage was analyzed with macroscopic injured area, deep damage was assessed with histopathology scores, and the hydrogen sulfide concentration in plasma was determined by colorimetric method. The results showed that pretreatment of NaHS significantly reduced the injured area and deep damage of the gastric mucosa induced by GI-R. However, NaHS did not significantly alter the levels of hydrogen sulfide in plasma 14 d after NaHS administration. The gastric protective effect of NaHS during reperfusion could be attenuated by glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker. However, K(ATP) opener pinacidil inhibited the GI-R-induced injury. These results suggest that exogenous hydrogen sulfide plays a protective role against GI-R injury in rats possibly through modulation of K(ATP) channel opening.

The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H(2)S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H(2)S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1-10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE(2) level. ACS14 reversed the decreased H(2)S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47(phox) and p67(phox). In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.

Hydrogen sulfide (H2S) is an endogenous gasotransmitter produced in mammalian cells. It is responsible for physiological functions in many organs and systems, with attention focused mainly on the cardiovascular and nervous systems. In the vascular system, H2S produces biphasic effects in regulation of vascular tone. At lower concentrations, it induces vasoconstriction predominantly via decreasing cyclic adenosine monophosphate in smooth muscle cell and inhibiting the production and bioavailability of nitric oxide. At higher concentrations, it produces vasorelaxation mainly through opening of KATP channels and induction of intracellular acidification. Scavenging reactive oxygen species and elevation of cyclic guanosine monophosphate are also implicated in the vasorelaxant response. This review presents an overview of the current knowledge of H2S in the vascular system, with special emphasis and discussion on the involvement of various signaling pathways and ion channels based on current understanding and reported literature till date.

Aim: To investigate expression of Bcl-2 and Bax in gastric ischemia-reperfusion (GI-R) and involvement of extracellular signal-regulated kinase (ERK) 1/2 activation., Methods: The GI-R model was established by ligature of the celiac artery for 30 min and reperfusion in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 0, 0.5, 1, 3, 6, 24, 48, and 72 h. Expression and distribution of Bcl-2 and Bax proteins were analyzed by immunohistochemistry and western blotting in gastric tissue samples after sacrifice., Results: Compared with controls, the percentage of positive cells and protein levels of Bcl-2 decreased in the early phases of reperfusion, reached its minimum at 1 h (P < 0.05); it then increased, reaching its peak at 24 h of reperfusion (P < 0.05). The pattern of Bax expression was opposite to that of Bcl-2. Bax expression increased after reperfusion, with its peak at 1 h of reperfusion (P < 0.05), and then it decreased gradually to a minimum at 24 h after reperfusion (P < 0.05). On the other hand, inhibition of activation of ERK1/2 induced by PD98059, a specific upstream MEK inhibitor, had significant effects on Bcl-2 and Bax in GI-R. Compared with GI-R treatment only at 3 h of reperfusion, PD98059 reduced the number of Bcl-2 positive cells (0.58% of R3h group, P < 0.05) and Bcl-2 protein level (74% of R3h group, P < 0.05) but increased the number of Bax-positive cells (1.33-fold vs R3h group, P < 0.05) and Bax protein level (1.35-fold of R3h group, P < 0.05)., Conclusion: These results indicated that the Bcl-2 and Bax played a pivotal role in the gastric mucosal I-R injury and repair by activation of ERK1/2.

Women with functional ovaries have a lower cardiovascular risk than men and postmenopausal women. However, oestrogen replacement therapy remains controversial. This study examined the effect of ovarian hormone deficiency and oestrogen replacement on ventricular myocyte contractile function and expression of beta-adrenoceptors (beta-ARs). Female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX) or sham operation (Sham). A subgroup of OVX rats received oestrogen (E2) replacement (40 microg kg(-1) day(-1)) for 4 weeks. Cardiomyocyte shortening was evaluated in basal conditions and in the presence of isoprenaline (ISO). The expression of beta-ARs was assessed by Western blotting. The presence of lactate dehydrogenase (LDH) activity in the coronary effluent was determined. Ovariectomy promoted body weight gain associated with reduced serum E2 and uterine weight, all of which were abolished by treatment with E2. Ovariectomy increased the amplitude of both basal and ISO-stimulated contractions, increased LDH release, upregulated beta1-AR expression and downregulated beta2-AR expression, all of which were restored by treatment with E2. A beta1-AR antagonist, CGP20712A, but not a beta2-AR antagonist, ICI118,551, significantly decreased the amplitude of ventricular myocyte shortening. Oestrogen decreased cardiomyocyte contraction and the expression of beta1-AR, and increased expression of beta2-AR, and all these effects were abolished by the E2 receptor antagonist, ICI182,780. These data suggest that oestrogen plays a cardioprotective role in female rat hearts subjected to ischaemia-reperfusion injury, and the effects of oestrogen are associated with decreased cardiomyocyte contraction and expression of beta1-AR, and increased expression of beta2-AR.

Aim: To investigate the effect of paraventricular nucleus (PVN) stimulation and the c-fos expression within PVN and nucleus tractus solitarius (NTS) of the rat following gastric ischemia/reperfusion injury (GI/RI)., Methods: The rat celiac artery was clamped for thirty minutes and reperfused for sixty minutes, using Fos immunohistochemical method (ABC method) examined the c-fos expression within PVN and NTS., Results: (1) Both electrical and chemical stimulation of the PVN obviously attenuated the GI/ RI. (2) Bilateral electrolytic lesion of NTS could eliminate the protective effect of electrical stimulation of the PVN. (3) The Fos-like immunoreactive neurons were increased in bilateral PVN and NTS by GI/RI., Conclusion: The function of PVN and NTS could be affected by the GI/RI noxious stimulation. PVN, NTS were involved in the regulation of GI/RI.

Aim: To investigate the effects of calcitonin gene-related peptide (CGRP), gastrin 17 (G17), bombesin (Bom), met-enkephalin (Met-enk), neuropeptide Y (NPY) and somatostatin (SS) on GMBF and the role of endogenous NO in increased GMBF induced by neuropeptides in rats., Methods: By hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and arterial infusion close to stomach or intracerebroventricular (icv) to microinject neuropeptides., Results: (1) Arterial infusions of CGRP and G17 (5, 50 and 100 pmol x min(-1)) increased GMBF significantly in dose-dependent manners. CGRP had more effective effect on increasing GMBF than that of G17. Intravenous pretreatment of L-nitro-L-arginine methyl ester (L-NAME) to inhibit the synthesis of endogenous NO could abolish completely or partially the increases in GMBF response to CGRP or G17 respectively. (2) Arterial infusions of Bom and Met-enk (50 and 100 pmol x min(-1)) increased GMBF significantly. The increases in GMBF induced by Bom or Met-enk were abolished completely or partially by pretreatment of L-NAME respectively. (3) Arterial infusion of NPY (5, 50 and 100 pmol x min(-1)) led to reduction of GMBF significantly in a dose-dependent manner. SS (50 and 100 pmol x min(-1)) also reduced GMBF significantly. (4) icv microinjection of CGRP (10 microg) and G17 (10 Microg) increased GMBF significantly. The increases in GMBF induced by icv microinjection of CGRP or G17 were blocked completely or partially respectively by pretreatments with L-NAME. (5) icv microinjection of NPY (10 microg) decreased GMBF significantly., Conclusion: Neuropeptides play important roles in the regulation of GMBF in rats and NO is involved in the increase of GMBF induced by some neuropeptides.

Aim and Methods: By hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent fibers, the roles of capsaicin-sensitive afferent fibers and endogenous NO in the gastric acid secretion and hyperemic response to intragastric distention were studied in rats., Results: (1) There was an increase in acid secretion associated with the increase in GMBF to intragastric distention. (2) Pretreatment with a high dose of capsaicin to ablate afferent fibers completely abolished the GMBF and partially inhibited the acid secretion during the intragastric distention. (3) The increase in GMBF to intragastric distention was completely blocked by pretreatment with L-NAME, whereas the acid secretion was significantly attenuated., Conclusion: Capsaicin-sensitive afferent fibers and endogenous NO are involved in the increases of gastric acid secretion and GMBF.

The effects of electrical and chemical stimulation and electrolytic lesion of lateral hypothalamic area (LHA) on gastric ischemia-reperfusion injury (GI-RI) were investigated in rats whose celiac arteries were clamped for 30 min and reperfused for 60 min by removal of the clamp. The results are as follows. (1) Electrical stimulation of LHA could aggravate GI-RI in an intensity-dependent manner by using 0.2, 0.4 or 0.6 mA current respectively. Microinjection of L-glutamic acid into LHA resulted in a similar effect to that of electrical stimulation of LHA on GI-RI. After electrolytic lesion of bilateral LHA, the area of gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) was smaller than that by electrical stimulation of LHA plus GI-R. (2) Dorsal vagal complex (DVC) lesion or vagotomy could eliminate the effect of electrical stimulation of LHA on GI-RI. (3) Electrical stimulation of LHA increased the content of malondialdehyde (MDA) but decreased the activity of superoxide dismutase (SOD) of ischemia-reperfusion (I-R) gastric mucosa. (4) Electrical stimulation of LHA plus gastric I-R increased gastric juice volume and total acid output, but there were no significant changes in acidity, pepsin activity and gastric barrier mucus. These results indicate that the LHA is an area in the CNS exerting aggravate effects on GI-RI. The DVC and vagus may be involved in the regulative effects of LHA on GI-RI. These effects are associated with increases in gastric mucosal MDA content, gastric juice volume, and total acid output, and a decrease in SOD activity.Acidity, pepsin activity and gastric barrier mucus do not seem to play an important role.

A rat model of gastric ischemia-reperfusion injury (GI-RI) was established by clamping the celiac artery for 30 min and allowing reperfusion for 1 h, on which the regulatory effect of the paraventricular nucleus (PVN) and its neural mechanisms were investigated. The results were: 1. Electrical stimulation of the PVN obviously attenuated the GI-RI. Microinjection of L-glutamic acid into PVN produced an effect similar to that of PVN stimulation. 2. Electrolytic ablation of the PVN aggravated the GI-RI. 3. Nucleus tractus solitarius (NTS) ablation could eliminate the protective effect of electrical stimulation of PVN on GI-RI. 4. Hypophysectomy did not alter the effect of electrical stimulation of PVN. 5. Vagotomy or sympathectomy both could increase the effect of PVN stimulation on GI-RI. These results indicate that the PVN participates in the development of GI-RI as a specific area in the CNS, exerting protective effects on the GI-RI. The NTS and vagus and sympathetic nerve may be involved in the regulative mechanism of PVN on GI-RI, but the PVN mechanism here is independent of the PVN-hypophyseal pathway.

The effects of paraventricular nucleus (PVN) stimulation and vasopressin on gastric ischemia-reperfusion injury (GI-RI) were investigated in male SD rats of which the celiac artery was clamped for 30 min and reperfused for 1 h by removal of the clamp. The results were as follows. Both electrical and chemical stimulation of the PVN obviously attenuated the GI-RI. Bilateral electrolytic lesion of the nucleus tractus solitarius (NTS) or microinjection of AVP-V(1) receptor antagonist into the NTS could eliminate the protective effect of electrical stimulation of the PVN on GI-RI. Hypophysectomy did not influence the effect of electrical stimulation of the PVN. Both vagotomy and sympathectomy could increase the effect of stimulating PVN on GI-RI. Microinjection of arginine-vasopressin (AVP) into the PVN also attenuated the effect on GI-RI. These results suggest that the PVN and AVP participate in the regulation of GI-RI and play an important role in protection against GI-RI. This protective effect of PVN on GI-RI might be mediated by activation of AVP-ergic neurons in the PVN, which release AVP from the descending projection fibers and activate the AVP-V(1) receptors on the NTS neurons. The vagus and sympathetic nerves are involved in the efferent pathway exerting their effects on GI-RI. Hypophysis does not seem to be involved in the protective effect of PVN stimulation.

By the use of hydrogen gas clearance technique, we have investigated the role of GMBF in the adaptive cytoprotection induced by intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol. The results were as follows: (1) intragastric perfusion with low concentration prior to high concentration of HCl plus ethanol led to an adaptive cytoprotection, i.e., the gross and the deep damage were decreased by 47.09% and 44.57% respectively, as compared with those caused by high concentration of HCl plus ethanol alone; correspondingly, GMBF also showed an adaptive hyperemic response, i.e., GMBF was increased by 28.02% as compared with that due to high concentration alone; (2) close arterial infusion of vasopressin blocked the adaptive hyperemic response and abolished the adaptive cytoprotection; (3) intravenous indomethacin reduced the basal GMBF, and abolished both the adaptive hyperemic response and cytoprotection; furthermore, the gross and deep damage were aggravated compared with that caused by high concentration alone. The results showed that the adaptive hyperemic response of gastric mucosa was involved in the adaptive cytoprotection and suggested that the adaptive cytoprotection of endogenous prostaglandin might be partially related to the increase of GMBF.

Using hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent neurons, the role of capsaicin-sensitive neurons in the gastric acid secretion and hyperemic response to intragastric peptone was investigated. The results were as follows: (1) there was an increase in acid secretion associated with the hyperemic response to intragastric peptone; (2) pretreatment with a high dose of capsaicin to ablate afferent neurons completely abolished the gastric hyperemic response to intragastric peptone and partially inhibited the acid secretion; (3) the gastric hyperemic response to intragastric peptone was completely blocked by pretreatment with L-nitro-arginine methyl ester (L-NAME), whereas the acid secretion was significantly attenuated; (4) inhibited effects of L-NAME on acid secretion and GMBF could be reversed by pretreatment with L-arginine (L-ARG); (5) pretreatment with atropine inhibited gastric acid output (GAO) and partially attenuated GMBF. These results suggested that capsaicin-sensitive afferent neurons and endogenous NO were involved in the gastric acid secretion and hyperemic response to intragastric peptone and the hyperemic response was mediated by both cholinergic and noncholinergic neurons.

The effect of electrical stimulation of hypothalamic paraventricular nucleus (PVN) on gastric mucosal lesion induced by RWIS (restraint + water-immersion stress) in rats was investigated. The main results were as follows: (1) Electrical stimulation of the PVN could obviously increase the stress gastric mucosal lesion. (2) Microinjection of L-glutamate into PVN could produce similar effect to that of PVN stimulation. (3) PVN lesion could significantly decrease the stress gastric mucosal lesion. (4) The above mentioned effects were attenuated by vagotomy or atropine injected subcutaneously. (5) A further study indicated that the gastric mucosal blood flow was reduced upon PVN stimulation, but no obvious changes of gastric juice volume, total acid output, pepsin activity and gastric barrier mucus were observed. The results mentioned above indicate that the PVN is one of the specific CNS areas capable of increasing the stress-induced gastric mucosal lesion mediated through the cholinergic fibers of the vagal nerve and related to decreased gastric mucosal blood flow, while gastric acid output, pepsin activity and gastric barrier mucus do not seem to play any important role.

In the present paper, effects of scopolia drugs (scopolamine, anisodine, anisodamine) on experimental gastric mucosal lesion models in rats were investigated. Scopolia drugs were found to be effective anti-ulcer agents in three experimental gastric ulcer models (i.e. cold-restraint stress induced ulcer, indomethacin induced ulcer and acetic acid induced chronic ulcer) in rats in a dose dependent manner. Biochemical analysis of gastric juice and blood showed that scopolia drugs could inhibit gastric acid secretion and pepsin activity, increase gastric barrier mucus and concentration of serum gastrin, suggesting that these actions may contribute to its anti-ulcer effect.