Search PubMed⌕ Search

Biomedical subjects

F Cosentino

Publications and source records attributed to F Cosentino.

At least 37 records · Page 2Linked to original sources
PubMed1999

Original technique for small colorectal tumor localization during laparoscopic surgery.

INTRODUCTION: Small colonic tumor localization and correct extension of colonic resection is critical in laparoscopic surgery. Currently used techniques are sometimes inconclusive and may carry some morbidity. We describe an original method of small tumor localization during laparoscopic colorectal operations through the use of preoperative clip applications by colonoscopy and intraoperative ultrasound of the colon. METHODS: Eight patients with small colonic lesions necessitating preoperative marking were included into this study. A two-step technique was used. Before the operation two metal clips were endoscopically applied proximally and distally to the lesion site. At surgery an intraoperative ultrasound examination of the colon or rectum surface was performed to localize the clips. Subsequent laparoscopic colon resection was performed. RESULTS: Endoscopic metallic clips were easily applied around the lesion in all cases without complications. No dislodgement of clips was documented. At surgery laparoscopic ultrasound visualized the clips in all cases. The examination took between 5 and 17 minutes with no specific morbidity. The lesions with the surrounding clips were always found in the resected specimen. CONCLUSIONS: Endoscopic metal clipping and intraoperative laparoscopic ultrasound proved to be an easy, safe, and accurate technique in locating small colonic tumors.

Colon↗
PubMed1998

Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats.

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The A23187-stimulated production of O2- and its superoxide dismutase product hydrogen peroxide were significantly higher, whereas nitric oxide release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to A23187 were significantly inhibited by catalase, and enhanced by superoxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications.

Animals↗
PubMed1998

Impaired vasorelaxant responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.

BACKGROUND: We have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the development of strokes in rats of a F2 hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats. OBJECTIVE: To investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats. DESIGN AND METHODS: In view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolated rings of aortas and internal carotid arteries obtained from stroke-prone and stroke-resistant spontaneously hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex-matched Wistar-Kyoto rats was also studied. RESULTS: Systolic blood pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar-Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular diet were comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar. CONCLUSION: The vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.

Animals↗
PubMed1998

Alterations to the nitric oxide pathway in the spontaneously hypertensive rat.

OBJECTIVES: To examine the role of nitric oxide in the cardiovascular system in spontaneous hypertension. In particular, we wanted to know whether the production of nitric oxide in the cardiovascular system of the spontaneously hypertensive rat is different from that of the normotensive Wistar-Kyoto rat and whether nitric oxide is biologically effective in this system. DESIGN: We studied various aspects of the L-arginine-nitric oxide pathway in the cardiovascular system of spontaneously hypertensive rats and Wistar-Kyoto rats. METHODS: To address the first objective we analysed the expression of endothelial nitric oxide synthase in the heart by Western blotting and the activity of constitutive nitric oxide synthase in resistance microvessels obtained from the mesenterium, both from spontaneously hypertensive rats and Wistar-Kyoto rats aged 14-18 weeks. We also analysed the concentration of the oxidative product of nitric oxide, nitrate, in plasma from these rats. To address the second objective, that is, to assess the bioactivity of nitric oxide, we studied the accumulation in tissue of cyclic guanosine 3',5'-monophosphate (GMP), as well as the acute and chronic effects of withdrawing the nitric oxide vasodilatory tone with the inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester on Wistar-Kyoto rats and spontaneously hypertensive rats. RESULTS: We found that the expression of endothelial nitric oxide synthase in the heart, the activity of constitutive nitric oxide synthase in resistance microvessels and the concentration of nitrate in plasma were all significantly higher in the spontaneously hypertensive rats. In contrast, neither cyclic GMP levels nor the effects of NG-nitro-L-arginine methyl ester were greater in the spontaneously hypertensive rat than they were in the Wistar-Kyoto rat. CONCLUSIONS: The nitric oxide pathway is upregulated in the resistance circulation and the heart of the spontaneously hypertensive rat by a mechanism involving induction of the constitutive nitric oxide synthase and overproduction of nitric oxide. However, nitric oxide is not sufficiently bioactive to stimulate the formation of cyclic GMP and to maintain an adequate nitric oxide-dependent vasodilatory tone.

Animals↗
PubMed1998

The classification of calcium antagonists and their selection in the treatment of hypertension. A reappraisal.

Calcium antagonists have become one of the most important advances in the treatment of hypertension since their introduction over 20 years ago. The increase in the number of available calcium antagonists (as new formulations of pre-existing drugs or new chemical entities) over recent years has contributed to an ever-changing scenario regarding their appropriate use compared with other antihypertensive agents. As a consequence of this evolving situation, several authors have proposed a 3-generation classification of calcium antagonists currently, or soon to be, marketed in several counties. The classification system is based among other variables, on chemical structure, tissue selectivity, administration frequency and duration of action. In this article, this classification is reviewed and updated on the basis of new information that is available. In addition, factors which influence the selection of calcium antagonists in the treatment of hypertension in specific patient populations are discussed. As well as pharmacodynamic and pharmacokinetic considerations, these factors also include previous experience with particular drugs in specific patient populations, cost of treatment and drug interactions. Among the dihydropyridine calcium antagonists, the first generation compounds have been clearly superseded and are not recommended for use in hypertensive patients. Whilst the second generation agents represent an adequate treatment, third generation calcium antagonists possess distinct advantages. Definitive confirmation of the role of calcium antagonists in hypertension lies in several ongoing large multicentre trials.

Antihypertensive Agents↗
PubMed1998

Tetrahydrobiopterin and endothelial function.

Tetrahydrobiopterin is an essential co-factor required for catalytic activity of nitric oxide synthases. A close link between tetrahydrobiopterin and nitric oxide synthesis has been recently demonstrated in a number of different cell types, including endothelial cells. The precise role of tetrahydrobiopterin in regulation of nitric oxide synthase activity is not completely understood; however, it may function as both an allosteric and redox co-factor. In peripheral and cerebral arteries, administration of tetrahydrobiopterin can stimulate production of nitric oxide. By contrast, in arteries depleted of tetrahydrobiopterin, nitric oxide production is impaired. Evidence indicates that, under certain pathological conditions, decreased availability of tetrahydrobiopterin may be responsible for a dysfunction of nitric oxide synthase leading to a shift in the balance between the production of protective nitric oxide and deleterious oxygen-derived free radicals. This concept may have important implications in understanding the mechanisms of endothelial dysfunction and oxidative vascular injury described in a number of vascular diseases, including atherosclerosis. This review will discuss the complex interaction between tetrahydrobiopterin and nitric oxide synthase and its role in the control of vascular tone.

Animals↗
PubMed1998

Endothelial dysfunction in diabetes mellitus.

Diabetes mellitus is associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Although the link between diabetes and cardiovascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. There is substantial evidence that vasodilatation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models of diabetes and in patients with insulin-dependent and non-insulin-dependent diabetes mellitus. NO is a principal factor involved in the antiatherosclerotic properties of the endothelium. NO interferes with key events in the development of atherosclerosis, such as vascular tone, monocyte and leukocyte adhesion to the endothelium, platelet-vessel wall interaction, and smooth muscle proliferation. Therefore, the pathogenesis of diabetic vascular disease may involve a reduced bioavailability of endothelium-derived NO. Although mechanisms by which diabetes contributes to endothelial dysfunction are currently unknown, it is likely that hyperglycemia, the hallmark of diabetes mellitus, may initiate this abnormality. Hyperglycemia-induced endothelial dysfunction may result from decreased production of NO, inactivation of NO by oxygen-derived free radicals, and/or increased production of endothelium-derived contracting factors, which oppose the protective activity of NO. This review summarizes evidence for endothelial dysfunction in diabetic patients and animals and the effects of prolonged exposure to elevated glucose in normal blood vessels and cultured endothelium. A better understanding of the mechanism(s) of hyperglycemia-induced endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbidity and mortality in this condition.

Animals↗
PubMed1997

High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells.

BACKGROUND: Hyperglycemia is a primary cause of premature vascular disease. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxations is likely to be involved. Little is known about the molecular mechanisms of hyperglycemia-induced endothelial dysfunction. METHODS AND RESULTS: This study was designed to determine the effect of hyperglycemia on the L-arginine/nitric oxide (NO) pathway. Expression of endothelial nitric oxide synthase (eNOS) mRNA and production of NO were studied in human aortic endothelial cells exposed to control levels (5.5 mmol/L) and high levels (22.2 mmol/L) of glucose for 5 days. We examined the effect of glucose on NO release by measuring changes in nitrite (NO2-) levels by Griess reaction. Superoxide anion (O2-) production was also examined by the ferrocytochrome c assay. NOS mRNA and protein expression, which were evaluated by reverse transcription-polymerase chain reaction and Western blotting, were approximately twofold greater in endothelial cells exposed to high glucose. Elevated glucose levels increased NO2- production by only 40% but increased the release of O2- by more than threefold. CONCLUSIONS: The present study demonstrates that prolonged exposure to high glucose increases eNOS gene expression, protein expression, and NO release. However, upregulation of eNOS and NO release is associated with a marked concomitant increase of O2- production. These results provide the molecular basis for understanding how chronic exposure to elevated glucose leads to an imbalance between NO and O2-. This may explain impaired endothelial function and be important for diabetic vascular disease.

Aorta↗
PubMed1997

Tetrahydrobiopterin restores endothelial function in hypercholesterolemia.

In hypercholesterolemia, impaired nitric oxide activity has been associated with increased nitric oxide degradation by oxygen radicals. Deficiency of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase, causes both impaired nitric oxide activity and increased oxygen radical formation. In this study we tested whether tetrahydrobiopterin deficiency contributes to the decreased nitric oxide activity observed in hypercholesterolemic patients. Therefore, L-mono-methyl-arginine to inhibit basal nitric oxide activity, serotonin to stimulate nitric oxide activity, and nitroprusside as endothelium-independent vasodilator were infused in the brachial artery of 13 patients with familial hypercholesterolemia and 13 matched controls. The infusions were repeated during coinfusion of L-arginine (200 microg/kg/min), tetrahydrobiopterin (500 microg/min), or the combination of both compounds. Forearm vasomotion was assessed using forearm venous occlusion plethysmography and expressed as ratio of blood flow between measurement and control arm (M/C ratio). Tetrahydrobiopterin infusion alone did not alter M/C ratio. Both the attenuated L-mono-methyl-arginine-induced vasoconstriction as well as the impaired serotonin-induced vasodilation were restored in patients during tetrahydrobiopterin infusion. Tetrahydrobiopterin had no effect in controls. In conclusion, this study demonstrates restoration of endothelial dysfunction by tetrahydrobiopterin suppletion in hypercholesterolemic patients.

Adult↗
PubMed1997

Common bile duct exploration and laparoscopic cholecystectomy: role of intraoperative ultrasonography.

BACKGROUND: In October 1993, to detect associated common bile duct (CBD) stones, we started an evaluation program of patients with symptomatic cholelithiasis who were candidates for laparoscopic cholecystectomy. STUDY DESIGN: We used a standard preoperative algorithm and a laparoscopic ultrasonographic (LUS) examination. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) was reserved for high-risk patients for CBD stones. Laparoscopic ultrasonographic examination during cholecystectomy was routinely performed to identify stones unsuspected preoperatively. Two-hundred-sixteen patients with symptomatic cholelithiasis were included in the study; 177 patients (82%) were at low risk for choledocholithiasis and 39 patients (18%) were at high risk and had preoperative ERCP. In 17 patients (43.5%) CBD stones were found, and in 16 patients (41%) they were removed by endoscopic sphincterotomy. RESULTS: In all patients, the main intra- and extrahepatic ducts were well documented by LUS, but in eight cases the distal tract of the CBD was not well-visualized. In eight patients, small stones were found in the CBD. A subsequent peroperative cholangiography or CBD exploration confirmed the diagnosis. In one patient, both LUS and cholangiography suspected a small stone; the CBD exploration did not confirm it (false positive). In two patients a small stone in the CBD was found during the followup period (two false negatives). An endoscopic sphincterotomy solved the problem. CONCLUSIONS: Laparoscopic ultrasonographic examination may be a real alternative to cholangiography during laparoscopic cholecystectomy: this may be reserved for selected instances on the basis of LUS findings. On the other hand, considerable ultrasonographic experience is required for LUS to be performed successfully.

Algorithms↗
PubMed1997

Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin.

We investigated the effects of aging, a cardiovascular risk factor, on vascular function with regard to endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), and endothelin (ET-1) in aorta and femoral artery of the rat. Concentration-response curves to acetylcholine, calcium ionophore A23187, norepinephrine, ET-1, big endothelin, sodium nitroprusside, and exogenous SOD were obtained. Expression of eNOS mRNA was analyzed by reverse-transcription polymerase chain reaction, SOD activity was assessed using a chemiluminescence-based cytochrome c assay, and ET-1 plasma concentrations were measured by radioimmunoassay. In aorta of old rats, relaxations to acetylcholine and calcium ionophore A23187, basal NO release, and expression of eNOS mRNA in aortic endothelial cells were reduced (P<.05). In femoral arteries, relaxations to acetylcholine were preserved, whereas basal release of NO was attenuated (P<.05). Aging selectively increased contractions to norepinephrine and functional endothelin converting enzyme activity and attenuated contractions to ET-1 in aortas but not femoral arteries. Vascular SOD activity was higher in the femoral artery (P<.05) and unaffected by aging. Plasma ET-1 levels increased and plasma SOD activity decreased with age (P<.05). Aging was associated with an anatomic heterogeneity of endothelial dysfunction, functional endothelin converting enzyme activity, and vascular SOD activity. Vascular function was impaired in the aorta but not the femoral artery, which may be related to lower eNOS mRNA expression and SOD activity. These data suggest differential regulation of the vascular aging process that may contribute to the anatomic heterogeneity of atherosclerosis.

Aging↗
PubMed1997

Portal hypertensive gastropathy: reproducibility of a classification, prevalence of elementary lesions, sensitivity and specificity in the diagnosis of cirrhosis of the liver. A NIEC multicentre study. New Italian Endoscopic Club.

OBJECTIVE: To classify elementary endoscopic lesions of portal hypertensive gastropathy, assess their reproducibility, prevalences, sensitivity and specificity in the diagnosis of cirrhosis of the liver. METHODS: 1) A classification of portal hypertensive gastropathy elementary lesions was defined. 2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3) Fifteen centres enrolled consecutive patients with or without cirrhosis of the liver and recorded portal hypertensive gastropathy pattern according to its location. RESULTS: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal hypertensive gastropathy prevalence was higher in patients with cirrhosis of the liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was 0.83. Portal hypertensive gastropathy was tentatively classified as mild or severe when mosaic-like pattern alone or red marks of any kind were present, respectively; this classification led to a further improvement in reproducibility. CONCLUSIONS: Our results suggest that a sufficient degree of agreement can be achieved in recording portal hypertensive gastropathy. Therefore, the New Italian Endoscopic Club classification should be used to evaluate the natural history of this condition.

Diagnosis, Differential↗
PubMed1996

Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery.

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.

Aging↗
PubMed1996

[The utilization of Medline for the solution of real clinical problems. A prospective study in Italy].

AIM: Measure of usefulness of Medline searches requested for clinical problems. METHODS: open prospective uncontrolled study lasted for 3 months. Collection of online or CD-ROM Medline searches operated by clinicians or librarians at 5 biomedical libraries. User interviews about use and usefulness of Medline, recorded with a closed-answer self-administered questionnaire, adapted from a U.S. National Library of Medicine product. RESULTS: Of the 6 participating libraries, one was excluded from analysis from data collection inadequacies. Among 668 searches, 55 (8.2%) were produced for real patients. Physicians judgement about clinical usefulness of their searches (available for 46 cases) indicate a significant importance for diagnostic evaluation (23%) and therapy administration (46%). After applying search results into clinical practice, clinicians think that positive outcomes are achieved in the doctor-patient-family relationship area (19%), a better use of health care system facilities is obtained (26%) and, less consistently, positive effects are perceived on longevity (5%), abnormality correction (10%), symptomatic relief (7%) and functional recovery (6%). CONCLUSION: Physicians judge that Medline searches actually can contribute to diagnosis and treatment of real patients, with significant benefits on the process of care, on doctor-patient relationship and on patient's health.

CD-ROM↗
PubMed1995

Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries.

BACKGROUND: The L-arginine/nitric oxide pathway plays a key role in the regulation of arterial tone. Biosynthesis of nitric oxide requires activation of nitric oxide synthase in the presence of tetrahydrobiopterin as a cofactor. Biochemical studies demonstrated that activation of purified nitric oxide synthase at suboptimal concentrations of tetrahydrobiopterin leads to production of hydrogen peroxide. The present experiments were designed to determine whether in coronary arteries inhibition of tetrahydrobiopterin synthesis may favor nitric oxide synthase-catalyzed production of hydrogen peroxide. METHODS AND RESULTS: Primary branches of canine left anterior descending artery were incubated for 6 hours in minimum essential medium in the presence or in the absence of the tetrahydrobiopterin synthesis inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP; 10(-2) mol/L). Arterial rings were suspended for isometric tension recording. Production of cGMP was measured by radioimmunoassay. Experiments were performed in the presence of indomethacin (10(-5) mol/L). During contractions to the thromboxane A2/prostaglandin H2 receptor agonist U46619 (10(-7) mol/L), calcium ionophore A23187 (10(-9) to 10(-6) mol/L) caused endothelium-dependent relaxations. A nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (3 x 10(-4) mol/L), significantly inhibited these relaxations. In DAHP-treated arteries, relaxations to A23187 and its stimulating effect on cGMP production were significantly reduced in the presence of catalase (1200 U/mL). By contrast, catalase did not exert any effect in rings incubated in the absence of DAHP. Furthermore, the inhibitory effect of catalase on A23187-induced relaxations was abolished when coronary arteries were incubated in the presence of DAHP plus a liposoluble analogue of tetrahydrobiopterin, 6-methyltetrahydropterin (10(-4) mol/L). CONCLUSIONS: The present study suggests that hydrogen peroxide may be a mediator of endothelium-dependent relaxations in coronary arteries depleted of tetrahydrobiopterin. This initially compensatory response, triggered by a dysfunctional nitric oxide synthase, may represent an important mechanism underlying oxidative vascular injury.

Amino Acid Oxidoreductases↗
PubMed1995

Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators.

In the blood-vessel wall, the endothelium plays a key functional role by generating several substances that modulate vascular smooth muscle tone, as well as growth, and platelet function. This review focuses on the role of the endothelial L-arginine/nitric oxide signal transduction pathway in the maintenance of vascular integrity. Functional alterations of this pathway may be important in cardiovascular disease, because depressed activity of this protective mechanism leads to impaired relaxation and is also associated with reduced antithrombotic properties of the endothelial layer. Many of the beneficial effects of ACE inhibitor therapy may be mediated through their ability to enhance the physiological roles of nitric oxide.

Angiotensin-Converting Enzyme Inhibitors↗