Current Applications of Bacteriocin.

Bacteriocins are multifunctional, ribosomally produced, proteinaceous substances with pronounced antimicrobial activity at certain concentrations. They are produced by bacteria and certain members of archaea to inhibit the growth of similar or closely related bacterial strains. These molecules have antimicrobial activity against pathogenic and deteriorating bacteria, which justifies their biotechnological potential. They are classified into 3 major classes based on their structural and physicochemical properties: class I bacteriocin, class II bacteriocin, and class III bacteriocin. Bacteriocins inhibit the growth of target organisms by functioning primarily on the cell envelope and by affecting gene expression and protein production within cells. The use of bacteriocins has been reported for the following: food preservation, diverse therapeutic purposes such as treatment of peptic ulcer, spermicidal agent, and woman care, anticancerous agent, veterinary use, skincare, and oral care, and also for plant growth promotion in agriculture among others.

Review of herbal medications with the potential to cause bleeding: dental implications, and risk prediction and prevention avenues.

Medicinal plant products have been used in health care since time immemorial. During the past three decades, the use of herbal supplements has been on the rise in the USA. A number of these products have been shown to possess the potential to interfere with blood clotting. This paper is a review of blood-thinning herbal supplements commonly used in the USA, accompanied by discussion of the dental implications of their use along with suggestions for prediction and prevention of the risk of bleeding. Twenty herbal supplements belonging to four pharmacological groups are identified and reviewed. While the majority (45%) of the supplements reviewed possesses antiplatelet properties, the remaining are dispersed among anticoagulant (15%), a combination of antiplatelet and anticoagulant (15%), and other diverse groups (25%). The literature reveals that most of the available information on blood-thinning herbs is based on in vitro experiments, animal studies, and individual clinical case reports. Some herbal effects are also speculated based on theoretical grounds. These observations, together with the deficiency of the law regulating herbal supplements, indicate limitations of the literature and the regulatory mechanisms related to these products, further implying the need for additional research and improved regulation. While emphasizing the dental implications of the findings reported in the literature, suggestions were made for prediction and prevention of the risk of bleeding caused by herbal medications, based on the concepts of predictive, preventive, and personalized medicine.

Khat: A Substance of Growing Abuse with Adverse Drug Interaction Risks.

The growing global availability of the stimulant shrub, khat, has aroused widespread concern. This paper is a review of possible adverse interactions between khat and conventional drugs. Khat chewing has been shown to reduce the bioavailabilities of orally co-administered antibiotics, ampicillin, amoxicillin, cephradine and tetracyclineHCl, and the antimalarial drug, chloroquine. The cardiovascular and central nervous system (CNS) stimulant effects of monoamine oxidase inhibitors (MAOI) and amphetamine-like drugs have been described to be enhanced by khat chewing. Khat is recognized to have the ability to counteract the effects of antihypertensive, antiarrhythmic and local anesthetic drugs, and to offset the cardioprotective action of aspirin. Depending on the amount or duration of consumption, khat has been reported to variably affect the actions of general anesthetics. Khat is likely to augment the effects and/or toxicity of different drugs due to its inhibitory action on the drug metabolizing enzyme CYP2D6. While specific mechanisms have been suggested for some of the khat-drug interactions reported, the mechanisms for other interactions are less clear. Despite the above observations, the literature reviewed is associated with a number of shortcomings, suggesting the need for further research and documentation on this area of knowledge. It is recommended that, in the interim, health care providers should be more familiar with the known and suspected adverse khat-drug interactions in order to optimally serve their patients who chew khat.

Khat and synthetic cathinones: Emerging drugs of abuse with dental implications.

The rising global availability of the stimulant and euphoric substances, khat and synthetic cathinones, has become a cause for concern in many countries, including the United States. Both substances are illegal in United States, although this has not deterred their use. Besides central nervous system effects, these drugs also cause sympathomimetic and orodental adverse effects, similar to those of amphetamine. Although synthetic cathinones are stronger than khat in most cases, the latter additionally contains tannins, which have astringent effects on tissues components, including those in the oral cavity. Recognizing the use prevalence and reported orodental adverse effects of khat and synthetic cathinones, dental practitioners should be more familiar with these substances to optimally treat and educate their patients abusing them. This paper reviews the pharmacology and adverse effects of khat and synthetic cathinones, along with the extent of their use in United States, with particular emphasis on dental implications.

Status of stem cells in diabetic nephropathy: predictive and preventive potentials.

BACKGROUND: Recruitment of stem cells to sites of tissue injury constitutes an important mechanism aimed at tissue repair and regeneration. However, it is not clear how the diabetic milieu affects the viability of endogenous stem cells. Thus, we tested the hypothesis that diabetes mellitus is associated with increased apoptosis which, in turn, contributes to reduction in stem cells and the manifestation of type 2 diabetic nephropathy. METHODS: Sixteen-week-old male obese type 2 diabetic db/db mice, and their appropriate controls, were used for assessment of the status of endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), and hematopoetic stem cells (HSCs) in the peripheral blood and renal tissue using specific cell markers. Further, we explored whether diabetic animals display greater apoptosis of stem cell subsets. RESULTS: The peripheral blood cells of db/db mice displayed reduction in EPCs (p < 0.05) compared to those of db/m controls. Further, kidney cells prepared from experimental groups also showed reductions in EPCs, MSCs, and HSCs. We also observed increased apoptosis of stem cell subsets in cells prepared from kidneys of db/db than those of db/m mice. CONCLUSIONS: The present study shows a similar pattern of decline in stem cell subsets in peripheral blood and kidneys of db/db mice, an effect likely related to increased apoptosis. Collectively, the results suggest that apoptosis of stem cells likely contributes to eventual manifestation of renal failure in diabetes mellitus. Monitoring of blood levels of stem cell subsets could predict failure of their reparative and protective effects and eventual manifestations of diabetic complications.

Effects of acrylic resin monomers on porcine coronary artery reactivity.

The purpose of the present investigation was to assess the reactivity of porcine coronary arteries under in vitro conditions following their exposure to methyl methacrylate (MMA) and hydroxyethyl methacrylate (HEMA) monomers. Confirming previous studies using rat aortas, both MMA and HEMA induced acute/direct relaxation of coronary ring preparations, which was partly dependent on the endothelium. With prolonged tissue exposure, both monomers caused time- and concentration-dependent inhibition of receptor-mediated contraction of the vascular smooth muscle caused by prostaglandin F2∝ (PGF2∝), with HEMA causing more inhibition than MMA. Hydroxyethyl methacrylate, but not MMA, also produced impairment of non-receptor-mediated contraction of the coronary smooth muscle induced by KCl. On the other hand, neither HEMA nor MMA altered relaxation of the smooth muscle produced by the direct-acting pharmacological agent, sodium nitroprusside (SNP). While exposure to HEMA impaired endothelium-dependent vasorelaxation caused by bradykinin (BK), MMA markedly enhanced this endothelial-mediated response of the arteries. The enhanced endothelial response produced by MMA was linked to nitric oxide (NO) release. In conclusion, with prolonged tissue exposure, MMA causes less pronounced effects/adverse consequences on coronary smooth muscle function relative to the effect of HEMA, while enhancing vasorelaxation associated with release of NO from the endothelium. Accordingly, MMA-containing resin materials appear to be safer for human applications than materials containing HEMA.

Mechanisms of load dependency of myocardial ischemia reperfusion injury.

Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further, systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately exacerbate ischemia reperfusion injury.

Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.

This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3] supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower in untreated db/db mice than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100-mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it causes moderate reduction in albuminuria, without affecting the histopathological appearance of the kidney and increasing the risk for DNA damage.

Herbal supplement use among adult dental patients in a USA dental school clinic: prevalence, patient demographics, and clinical implications.

OBJECTIVE: This study assessed the frequency and patterns of utilization of herbal supplement products by adult dental patients at a USA dental school clinic. STUDY DESIGN: A self-reporting questionnaire was used to collect patient demographics and frequency of herbal supplement utilization along with other information. The questionnaire was distributed and collected at a dental visit. Herbal utilization was related to patient demographics using descriptive analysis. The clinical implications of the findings are discussed. RESULTS: Out of 1,240 questionnaires, 1,119 were returned as completed. Of these, 12.6% reported using ≥1 of 21 herbal products. The majority of the users were middle-aged educated caucasian women. Green tea, garlic, echinacea, ginkgo biloba, and ginseng were the top 5 products used. Mostly, supplements were consumed in combination with drugs. CONCLUSIONS: The type, prevalence, and frequency of herbal supplement utilization by adult dental patients in this USA dental clinic were generally similar to those reported for other population groups. This observation, coupled with the documented effects of the commonly used herbal products, should alert dental health caregivers to inquire about herbal supplement use when evaluating or treating their patients.

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Role of taurine in the vasculature: an overview of experimental and human studies.

Taurine is a sulfur-containing amino acid-like endogenous compound found in substantial amounts in mammalian tissues. It exerts a diverse array of biological effects, including cardiovascular regulation, antioxidation, modulation of ion transport, membrane stabilization, osmoregulation, modulation of neurotransmission, bile acid conjugation, hypolipidemia, antiplatelet activity and modulation of fetal development. This brief review summarizes the role of taurine in the vasculature and modulation of blood pressure, based on experimental and human studies. Oral supplementation of taurine induces antihypertensive effects in various animal models of hypertension. These effects of taurine have been shown to be both centrally and peripherally mediated. Consistent with this, taurine produces endothelium-dependent and independent relaxant effects in isolated vascular tissue preparations. Oral administration of taurine also ameliorates impairment of vascular reactivity, intimal thickening, arteriosclerosis, endothelial apoptosis, oxidative stress and inflammation, associated primarily with diabetes and, to a lesser extent with obesity, hypertension and nicotine-induced vascular adverse events. In rat aortic vascular smooth muscle cells (VSMCs), taurine acts as an antiproliferative and antioxidant agent. In endothelial cells, taurine inhibits apoptosis, inflammation, oxidative stress and cell death while increasing NO generation. Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients. However, despite these favorable findings, there is a need to further establish certain aspects of the reported results and also consider addressing unresolved related issues. In addition, the molecular mechanism (s) involved in the vascular effects of taurine is largely unknown and requires further investigations. Elucidation of the mechanisms through which taurine affects the vasculature could facilitate the development of therapeutic and/or diet-based strategies to reduce the burdens of vascular diseases.

Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats.

Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

Endothelial dysfunction in diabetes: potential application of circulating markers as advanced diagnostic and prognostic tools.

Endothelial dysfunction is a predisposing factor for vascular disease in diabetes, which contributes significantly to the mortality of diabetic patients. The currently utilized assessment methods of endothelial function/dysfunction in humans are associated with various limitations. Circulating endothelial-derived/associated markers have been proposed as potential alternatives for evaluation of the endothelium in condition of vascular disorders. These indicators include von Willebrand factor, soluble thrombomodulin, soluble E-selectin, asymmetric dimethylarginine, tissue plasminogen activator, endothelial microparticles, circulating endothelial cells and circulating endothelial progenitor cells. While tentative evidence is available for most of these biomarkers to serve as reliable sources of information, their usefulness for routine clinical applications has not yet been established. Thus, circulating endothelial markers are currently the subject of intense research interest and it is anticipated that as more information becomes available their improved quantification will provide a suitable diagnostic and prognostic tool for vascular events in diabetes and related diseases.

P1 (adenosine) purinoceptor assays.

P1 purinoceptors, or adenosine (ADO) receptors, mediate the biological effects of the endogenous nucleoside, ADO and its analogs. ADO works through four receptor subtypes: A(1), A(2A), A(2B), and A(3). Isolated tissue assays used for the pharmacological characterization of ADO receptors based on functional responses are described in this unit. The guinea pig atrium, pig coronary artery, guinea pig aorta ,and mouse aorta have been used for the characterization of ADO receptor subtypes.

Effects of taurine on the reactivity of aortas from diabetic rats.

The effects of the semi-essential amino acid-like nutrient, taurine, on alterations in the reactivities of aortas from male rats with chronic streptozotocin-induced diabetes were examined under in vitro conditions. In the absence of taurine, the contractile responsiveness of endothelium-denuded aortic rings from diabetic rats to norepinephrine, but not KCl, was enhanced compared to controls. This effect of norepinephrine on the diabetic rat aorta appeared to be associated with increased release of intracellular calcium, influx of extracellular calcium and protein kinase C-mediated responses. Incubation of endothelium-denuded aortic rings with 10 mM, but not 5 mM, taurine for 2 h reduced the augmented contractile responses of the tissues from diabetic rats to norepinephrine close to control levels, and this was associated with inhibition of responses linked to the release and influx of calcium, and protein kinase C activation. Endothelium-dependent relaxation of aortas from diabetic rats to acetylcholine was depressed relative to controls. This effect of diabetes was ameliorated close to control levels by incubating the tissues with 10 mM, but not 5 mM, taurine for 2 h. Incubation of nondiabetic rat aortic rings with 45 mM glucose for 3 h caused enhancement of contraction of the vascular smooth muscle to phenylephrine and impairment of endothelium-mediated vasorelaxation to acetylcholine, as compared to control responses. Co-incubation of the tissues with 5-10 mM taurine concentration-dependently reduced the alterations in both contractile and relaxant responses caused by high glucose. Overall, the data suggest that taurine ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for taurine's potential as a therapeutic agent for the prevention or amelioration of vascular disorders in diabetes.

Vascular reactivity changes in glucose-intolerant rat.

The vascular effects of glucose-intolerance were investigated using the neonatal streptozotocin-treated (nSTZ) rat model. Glucose-intolerance was initiated by administration of STZ (90 mg/kg, IP) into 2-day-old male rats. Aortic reactivity was assessed in vitro at 3 and 6 months of age. Both the 3- and 6-month-old nSTZ rats displayed higher blood glucose levels in response to a glucose challenge. At 3 months of age, aortic responsiveness to both norepinephrine and acetylcholine was not altered. However, at 6 months of age, the responses of endothelium-denuded aortas from nSTZ rats to norepinephrine and serotonin were enhanced compared to controls. Endothelium-mediated relaxation of aortas from these animals to acetylcholine was also augmented, and this effect was linked to NO release. Although norepinephrine did not elicit enhancement of aortic contraction in calcium-free medium in 6-month-old nSTZ rats, the responses to both maximum and submaximum concentrations of the agonist after readdition of calcium were greater in these tissues than in control preparations. Pretreatment of aortas with calphostin C eliminated the difference in NE-induced contraction between the control and experimental groups. Although the concentration-response curves for phorbol 12,13-dibutyrate were not different between the 2 groups, the responses of the aortas from 6-month-old nSTZ rats to a submaximum concentration of the phorbol ester were enhanced relative to controls, and this enhancement was normalized with calphostin C. Overall, the data suggest that glucose-intolerance of sufficient duration causes increases in vascular reactivity to agonists. While these findings warrant further investigations, such vascular alterations during the prediabetes stage of glucose intolerance can be a predisposing factor for the eventual development of cardiovascular complications.

Roles of nitric oxide and prostacyclin in triethyleneglycol dimethacrylate (TEGDMA)-induced vasorelaxation.

OBJECTIVES: Most dental resinous materials contain the diluent monomer triethyleneglycol dimethacrylate (TEGDMA), which has been reported to be bioactive. Previously, it was demonstrated that TEGDMA induces vasorelaxation. The present study examines the mechanism(s) of the TEGDMA-induced vasorelaxation by measuring vascular nitrite and prostacyclin levels. METHODS: Nitrite and prostacyclin levels were assayed in rat aortic tissues in response to TEGDMA. The involvement of guanylyl and adenylyl cyclases in TEGDMA-induced aortic vasorelaxation was determined using the enzyme inhibitors 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), respectively. RESULTS: TEGDMA enhanced the levels of nitrites in endothelium-intact and that of protacyclin in both endothelium-intact and denuded rat aortas. The increase in nitrites was associated with endothelium-dependent aortic relaxation mediated via the activation of guanylyl cyclase, while the increase in prostacyclin was associated with both endothelium-dependent and independent relaxation linked to adenylyl cyclase stimulation. SIGNIFICANCE: Data from the present investigation can be relevant to dental practice employing materials containing TEGDMA by providing insights into the vasorelaxant effect of the monomer following placement of the materials in the oral cavity. Additional studies that are more relevant to the clinical situation are required to confirm these initial results and further explore their implications.

Vasorelaxant effect of resin-based, single-bottle dentin bonding systems.

Single-bottle dentin bonding systems are currently in wide use. Because these materials are sometimes inadvertently placed on microscopic pulp exposures while at other times deliberately on frank exposures, their effects on pulpal soft tissues need to be evaluated. The present study assessed the vascular effects of 3M Single Bond (3MSB) and Prime & Bond NT (PBNT), using rat aortic ring preparations. It is hypothesized that these bonding agents induce relaxation of these preparations. Both 3MSB and PBNT caused endothelium-dependent and -independent relaxations in a concentration-dependent manner. The endothelium-dependent relaxation was associated with the release of nitric oxide. However, the responses to both agents did not involve the generation of prostanoids or KATP channel activation. At relatively low concentrations, the responses of endothelium-denuded tissues to 3MSB were greater than those to PBNT, indicating certain differences in the vascular action between these products. The data suggest that 3MSB and PBNT interfere with vascular function by causing vasorelaxation via mechanisms occurring in the smooth muscle and endothelium, including the release of nitric oxide. Among others, this effect may promote bleeding if these adhesives are placed on pulp exposures.

Taurine depletion alters vascular reactivity in rats.

We recently showed that chronic taurine supplementation is associated with attenuation of contractile responses of rat aorta to norepinephrine and potassium chloride. However, the potential involvement of endogenous taurine in modulation of vascular reactivity is not known. Therefore, we examined the effect of beta-alanine-induced taurine depletion on the in vitro reactivity of rat aorta to selected vasoactive agents. The data indicate that both norepinephrine- and potassium-chloride-induced maximum contractile responses of endothelium-denuded aortae were enhanced in taurine-depleted rats compared with control animals. However, taurine depletion did not affect tissue sensitivity to either norepinephrine or potassium chloride. By contrast, sensitivity of the endothelium-denuded aortae to sodium nitroprusside was attenuated by taurine depletion. Similarly, taurine deficiency reduced the relaxant responses of endothelium-intact aortic rings elicited by submaximal concentrations of acetylcholine, and this effect was associated with decreased nitric oxide production. Taken together, the data suggest that taurine depletion augments contractility but attenuates relaxation of vascular smooth muscle in a nonspecific manner. Impairment of endothelium-dependent responses, which is at least in part associated with reduced nitric oxide generation, may contribute to the attenuation of the vasorelaxant responses. These vascular alterations could be of potential consequence in pathological conditions associated with taurine deficiency.