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C Napoli

Publications and source records attributed to C Napoli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Protease-activated receptor-2 modulates myocardial ischemia-reperfusion injury in the rat heart.

Protease-activated receptor-2 (PAR-2) is a member of seven transmembrane domain G protein-coupled receptors activated by proteolytic cleavage whose better known member is the thrombin receptor. The pathophysiological role of PAR-2 remains poorly understood. Because PAR-2 is involved in inflammatory and injury response events, we investigated the role of PAR-2 in experimental myocardial ischemia-reperfusion injury. We show for the first time that PAR-2 activation protects against reperfusion-injury. After PAR-2-activating peptide (2AP) infusion, we found a significant recovery of myocardial function and decrease in oxidation at reflow. Indeed, the glutathione cycle (glutathione and oxidized glutathione) and lipid peroxidation analysis showed a reduced oxidative reperfusion-injury. Moreover, ischemic risk zone and creatine kinase release were decreased after PAR-2AP treatment. These events were coupled to elevation of PAR-2 and tumor necrosis factor alpha (TNFalpha) expression in both nuclear extracts and whole heart homogenates. The recovery of coronary flow was not reverted by L-nitroarginine methylester, indicating a NO-independent pathway for this effect. Genistein, a tyrosine kinase inhibitor, did not revert the PAR-2AP effect. During early reperfusion injury in vivo not only oxygen radicals are produced but also numerous proinflammatory mediators promoting neutrophil and monocyte targeting. In this context, we show that TNFalpha and PAR-2 are involved in signaling in pathophysiological conditions, such as myocardial ischemia-reperfusion. At the same time, because TNFalpha may exert pro-inflammatory actions and PAR-2 may constitute one of the first protective mechanisms that signals a primary inflammatory response, our data support the concept that this network may regulate body responses to tissue injury.

Animals↗
PubMed2000

Ergonomics, gerontechnology, and design for the home-environment.

An ergonomic approach could improve the quality of life and activities in daily living. Gerontechnology reduces the effects of age-related impairments with technological devices and particular design for the home-environment. Physiological decline with increasing age renders the daily activities at home more difficult. This paper highlights some "common sense" and specific design suggestions in the entrance and kitchen, aimed to increase the self-sufficiency of elderly people. We suggest that gerontechnology may have a particular role in the improvement of comfort and safety for aged people.

Activities of Daily Living↗
PubMed2000

Pharmacological modulation, preclinical studies, and new clinical features of myocardial ischemic preconditioning.

The term "ischemic preconditioning (PC)" was first applied to canine myocardium subjected to brief episodes of ischemia and reperfusion that tolerated a more prolonged episode of ischemia better than myocardium not previously exposed to ischemia. Protective effect of myocardial ischemic PC was demonstrated in several animal species, resulting in the strongest endogenous form of protection against myocardial injury, jeopardized myocardium, infarct size, and arrhythmias other than early reperfusion. New onset angina before acute myocardial infarction, episodes of myocardial ischemia during coronary angioplasty or bypass surgery, and the "warm-up" phenomenon may represent clinical counterparts of the PC phenomenon in humans. Here, we have attempted to summarize pharmacological modulation, preclinical studies, and new clinical features of ischemic PC. To date, the pathophysiological basis of the "chemical PC" is still not well established, and "putting PC in a bottle" for clinical applications still remains a new pharmacological venture.

Aged↗
PubMed2000

Inflammation-coagulation network: are serine protease receptors the knot?

Following an injury, the body recruits a mechanism to delimit and repair tissue damage; this phenomenon is known as inflammation. Among the several different pathways that are activated during this process, which is necessary for survival, activation of the coagulation pathway is a key feature. In fact, clinical changes in blood fluidity have been closely related to ongoing inflammation. Recent evidence suggests that serine protease receptors might play a major role in the host defence mechanism at the interface between coagulation and inflammation.

Animals↗
PubMed2000

Exercise training restores ischemic preconditioning in the aging heart.

OBJECTIVES: To investigate the effects of ischemic preconditioning in hearts from adult and both sedentary and trained senescent rats. BACKGROUND: Ischemic preconditioning does not prevent postischemic dysfunction in the aging heart, probably because of reduction of cardiac norepinephrine release. Exercise training can reverse the age-related decrease of norepinephrine production. METHODS: We investigated the effects on mechanical parameters of ischemic preconditioning against 20 min of global ischemia followed by 40 min of reperfusion in isolated perfused hearts from adult (six months) and sedentary or trained (six weeks of graduated swim training) senescent (24 months) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. RESULTS: Final recovery of percent-developed pressure was significantly improved after preconditioning in adult hearts (91.6+/-9.6%) versus unconditioned controls (54.2+/-5.1%, p<0.01). The effect of preconditioning on developed pressure recovery was absent in sedentary but present in trained senescent hearts (39.6+/-4.1% vs. 64.3+/-7.1%, p<0.05). Norepinephrine release significantly increased after preconditioning in adult and in trained but not in sedentary senescent hearts. The depletion of myocardial norepinephrine stores by reserpine abolished preconditioning effects in adult and trained senescent hearts. CONCLUSIONS: In adult and trained but not in sedentary senescent hearts, preconditioning reduces postischemic dysfunction and is associated with an increase in norepinephrine release. Preconditioning was blocked by reserpine in both adult and trained senescent hearts. Thus, exercise training may restore preconditioning in the senescent heart through an increase of norepinephrine release.

Aging↗
PubMed2000

Clinicopathologic features and FHIT gene expression in sporadic colorectal adenocarcinomas.

BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. METHODS: FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene. RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.

Acid Anhydride Hydrolases↗
PubMed2000

Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells.

Apoptosis of arterial cells induced by oxidized low density lipoproteins (OxLDL) is thought to contribute to the progression of atherosclerosis. However, most data on apoptotic effects and mechanisms of OxLDL were obtained with extensively oxidized LDL unlikely to occur in early stages of atherosclerotic lesions. We now demonstrate that mildly oxidized LDL generated by incubation with oxygen radical-producing xanthine/xanthine oxidase (X/XO) induces apoptosis in primary cultures of human coronary endothelial and SMC, as determined by TUNEL technique, DNA laddering, and FACS analysis. Apoptosis was markedly reduced when X/XO-LDL was generated in the presence of different oxygen radical scavengers. Apoptotic signals were mediated by intramembrane domains of both Fas and tumor necrosis factor (TNF) receptors I and II. Blocking of Fas ligand (FasL) reduced apoptosis by 50% and simultaneous blocking of FasL and TNF receptors by 70%. Activation of apoptotic receptors was accompanied by an increase of proapoptotic and a decrease in antiapoptotic proteins of the Bcl-2 family and resulted in marked activation of class I and II caspases. Mildly oxidized LDL also activated MAP and Jun kinases and increased p53 and other transcription factors (ATF-2, ELK-1, CREB, AP-1). Inhibitors of Map and Jun kinase significantly reduced apoptosis. Our results provide the first evidence that OxLDL-induced apoptosis involves TNF receptors and Jun activation. More important, they demonstrate that even mildly oxidized LDL formed in atherosclerotic lesions may activate a broad cascade of oxygen radical-sensitive signaling pathways affecting apoptosis and other processes influencing the evolution of plaques. Thus, we suggest that extensive oxidative modifications of LDL are not necessary to influence signal transduction and transcription in vivo.

Apoptosis↗
PubMed2000

Determination of atherogenesis in apolipoprotein E-knockout mice.

BACKGROUND AND AIM: Genetically-modified mice are the preferred model for studies on atherogenesis. Conventional procedures for determining lesion size and composition may be not very accurate, especially when only very small lesions are present. We provide here a detailed characterization of lesion components and the computer-assisted quantitative determination of atherogenesis in apolipoprotein E-knockout (apoE-/-) mice. METHODS AND RESULTS: Atherosclerotic lesions were detected at typical predilection sites in the aorta: the small curvature of the arch, the orifices of the brachiocephalic trunk, the left subclavia and common carotid artery, the branch sites of the mesenteric and renal arteries, the abdominal aorta, and the iliac bifurcation. We found that these lesions covered 20% of the aortic surface of apoE-/- on average compared with 1% of the wild type C57BL/6 mice (p < 0.00001). As expected, immunocytochemistry revealed "oxidation-specific" epitopes, i.e. epitopes generated during the oxidation of LDL and other lipoproteins, in aorta from apoE-/- mice. CONCLUSIONS: Although some limitations may reduce the applicability of results obtained in mice to humans, the apoE-/- mouse appears to be suitable for investigation of the role of apolipoproteins, enzymes and receptors involved in lipid metabolism, lipid oxidation, vascular cells and their secretory products as well as the possible role of antioxidants and gene-therapy in reducing atherogenesis.

Animals↗
PubMed1999

Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study.

BACKGROUND: Children generally have low cholesterol and no clinical manifestations of atherosclerosis, but fatty-streak formation begins in fetuses and is greatly increased by maternal hypercholesterolaemia during pregnancy. In the FELIC study we assessed the evolution of such lesions during childhood. METHODS: Computer-assisted imaging was used to measure the area of the largest individual lesion and the cumulative lesion area per section in serial cross-sections through the entire aortic arch and abdominal aorta of 156 normocholesterolaemic children aged 1-13 years, who died of trauma and other causes. Children were classified by whether their mother had been normocholesterolaemic (n=97) or hypercholesterolaemic (n=59) during pregnancy. Atherosclerosis was correlated with 13 established or potential risk factors. Findings The largest fatty streaks in the aortic arch of children younger than 3 years of hypercholesterolaemic mothers were 64% smaller than those previously found in corresponding fetuses (p<0.0001), which suggests that fetal fatty streaks may regress after birth. In the two groups, lesion size in the aortic arch and abdominal aorta increased linearly with age (r=0.87-0.98). However, lesions progressed strikingly faster in children of hypercholesterolaemic mothers than in those of normocholesterolaemic mothers (p<0.0001). Conventional risk factors for atherosclerosis in children or mothers correlated with lesion size, but did not account for the faster progression of atherogenesis in normocholesterolaemic children of hypercholesterolaemic mothers. INTERPRETATION: Our results suggest that maternal hypercholesterolaemia during pregnancy induces changes in the fetal aorta that determine the long-term susceptibility of children to fatty-streak formation and subsequent atherosclerosis. If so, cholesterol-lowering interventions in hypercholesterolaemic mothers during pregnancy may decrease atherogenesis in children.

Adolescent↗
PubMed1999

Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries.

BACKGROUND: Atherosclerotic lesions in intracranial arteries occur later and are less extensive than in extracranial arteries. To investigate potential mechanisms responsible for this difference, in particular the atherogenic response to hypercholesterolemia and LDL oxidation, we compared the extent of fatty streak formation and the composition of these very early lesions in intracranial arteries of human fetuses from normocholesterolemic and hypercholesterolemic mothers with those in extracranial arteries. METHODS AND RESULTS: Lesions were quantified by computer-assisted image analysis of 30 oil red O-stained sections, each from the middle cerebral, basilar, and common carotid arteries and the abdominal aorta of human fetuses (spontaneous abortions and premature newborns who died within 12 hours of birth; both of fetal age 6.2+/-1.3 months) from 43 hypercholesterolemic mothers and 34 normocholesterolemic mothers. Macrophages, apolipoprotein B, and 2 epitopes of oxidized LDL in lesions were determined immunocytochemically. Activities of superoxide dismutase, catalase, and glutathione peroxidase in the arterial wall were also determined. Lesion numbers and sizes were dramatically greater in the abdominal aorta (area of the largest lesion per section: 66.5+/-10.9 x10(3) microm2) and the carotid (11. 6+/-5.3 x10(3) microm2) than in the basilar and middle cerebral artery (0.4+/-0.1 and 0.8+/-0.2 x10(3) microm2, respectively; P<0. 0001). Hypercholesterolemia resulted in a significant increase of lesion size in extracranial arteries but only a marginal increase in intracranial arteries. In analogy, hypercholesterolemia induced a much greater increase in the intimal presence of macrophages, apolipoprotein B, and oxidized LDL (oxidation-specific epitopes) in extracranial than in intracranial arteries. Immunocytochemistry did not indicate that lesions of intracranial arteries contain relatively less oxidized LDL than similar-size lesions of extracranial arteries. Activities of Mn-superoxide dismutase but not of Zn-superoxide dismutase, catalase, or glutathione peroxidase were significantly higher in both intracranial arteries. CONCLUSIONS: Exposure to hypercholesterolemia during fetal development results in extensive formation of fatty streaks in extracranial but not intracranial arteries. The fact that such a difference in lesion formation occurs in the absence of many other atherogenic risk factors found later in life suggests that differences in the atherogenic response to hypercholesterolemia are an important contributor to the slower onset of the disease in intracranial vessels in adults. Fetal arteries may allow elucidation of the mechanisms responsible, for example, better protection of intracranial arteries against free radical-mediated atherogenic processes.

Abortion, Spontaneous↗
PubMed1999

Age-related decrease in cardiac tolerance to oxidative stress.

Oxygen radical-mediated injury has been implicated in the process of cardiac aging. We investigated the tolerance to oxidative stress of hearts from rats of different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30 min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 microM), followed by a 15 min wash-out. H2O2 infusion resulted in a significantly larger increase in end-diastolic pressure in hearts of 6- and 12-month-old rats than 3 months (P<0.01). In addition, developed pressure and rate-pressure product decreased more evidently in 12-month-old hearts (P<0.01 vs 3 and 6 months). Arrhythmia analysis showed higher score in hearts of 12- and 6-month-old rats with respect to 3-month-old animals (P<0.05). Cardiac release of oxidized glutathione (an index of the ability of the heart to inactivate oxygen metabolites) was significantly lower in hearts from rats of 6 and 12 months than in younger animals (P<0.001). Finally, cardiac concentrations of the scavenger enzymes glutathione peroxidase and Mn-superoxide dismutase also significantly decreased with age. In conclusion, in rat heart metabolic and functional tolerance toward oxidative stress decreases with age. This phenomenon may contribute to the development of cardiovascular alterations with increasing age.

Aging↗
PubMed1999

Loop diuretics enhance the secretion of prostacyclin in vitro, in healthy persons, and in patients with chronic heart failure.

BACKGROUND: Previous studies suggest that the acute haemodynamic effects of loop diuretics are due to a direct dilation of blood vessels and are not related to diuretic properties, but possibly to prostaglandin secretion. OBJECTIVES: We investigated whether in vitro human endothelial and renal epithelial cells responded to torasemide or furosemide with enhanced secretion of the vasodilator prostaglandin prostacyclin (PGI2). We also investigated the effects of loop diuretics on plasma concentrations of PGI2 and its physiological antagonist thromboxane after 25 min of administration of drugs in 44 patients with congestive heart failure (CHF) and 44 healthy volunteers. METHODS: The PGI2 levels were measured after extraction in ethyl acetate by RIA as levels of 6-KetoPGF1alpha, a stable metabolite from a non-enzymatic degradation. TxB2 concentration, the stable hydrolysis product of TxA2, was also measured by RIA. RESULTS: In human endothelial and renal epithelial cells, both loop diuretics induced an increase of 6-KetoPGF1alpha secretion that reached a peak after about 5 min and remained stable for 30 min of exposure to the drugs. The magnitude of the phenomenon was lesser in epithelial than in endothelial cells. Moreover, in both cell lines, there was a significantly higher secretion of 6-KetoPGF1alpha to torasemide than furosemide (P < 0.05). Concentrations of 6-KetoPGF1alpha at baseline were similar between the groups of CHF patients receiving the two different drugs. After 25 min of both drugs, 6-Keto-PGF1alpha significantly increased (P < 0.01), and this was significantly higher in patients treated with 10 mg of torasemide (P < 0.05 vs furosemide). Levels of PGI2 at baseline were lower in healthy controls than those reached by CHF patients and similar between groups. After 25 min of both drugs, PGI2 plasma levels were significantly increased (P < 0.01). Baseline values of TxB2 were significantly higher in CHF patients compared with controls (P < 0.01 vs respective groups). and, more importantly, furosemide but not torasemide increased TxB2 levels in patients and controls (P < 0.05 vs baseline). CONCLUSIONS: Our study is the first demonstration in human tissue of increased secretion of PGI2 both in vitro and in vivo, after torasemide or furosemide administration. This phenomenon, which may explain in part the vasodilatory effects of these drugs, was more evident with torasemide and was reached at lower concentrations of the drug. Accordingly, we also found that furosemide but not torasemide stimulated the release of the PGI2 physiological antagonist thromboxane in CHF patients and healthy controls.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Beneficial effects of ACE-inhibition with zofenopril on plaque formation and low-density lipoprotein oxidation in watanabe heritable hyperlipidemic rabbits.

The effects of angiotensin-converting enzyme (ACE)-inhibition with zofenopril on the development of atherosclerosis and low-density lipoprotein (LDL) oxidation were determined in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Rabbits received either placebo (n = 6) or 0.5 mg/kg/day of zofenopril (n = 6). After 6 weeks of treatment, the computer-assisted analysis revealed that zofenopril reduced the aortic and common carotid corrected cumulative lesion area by 34% and 39%, respectively (p < 0.05 vs placebo-treated group). The intimal/medial ratio of the largest fatty streaks was 0.426+/-0.158 in the zofenopril-treated group and 0.875+/-0.238 in the placebo-treated group (p < 0.05). Furthermore, we found in the zofenopril-treated group smaller lesions with an intimal/medial ratio of zofenopril also reduced plasmatic LDL oxidation, as shown by significant reduction of malondialdehyde content (p < 0.01) and relative agarose gel mobility (p < 0.05), as well as by the prolongation of the lag-time (p < 0.05). Compared to zofenopril-treated rabbits, arterial sections of the placebo-group had significant increase in the intimal presence of macrophages-derived foam cells (p < 0.05), ox-LDL (p < 0.01), and native LDL (p < 0.01) detected by immunocytochemistry with RAM-11, MDA2 and NP1533975 monoclonal antibodies, respectively. To investigate the amount of platelet accumulation in the atherosclerotic plaque we also measured platelet-associated radioactivity. Autologous platelets were labeled with 111Indiumoxine and injected intravenously. After 2 hours, WHHL were sacrificed and arterial sections were counted for platelet-associated radioactivity. In the placebo-treated group, platelet radioactivity was 0.52+/-0.12 equivalent of radioactivity per mg of tissue in the common carotid and 0.25+/-0.18 in the abdominal aorta; in contrast, rabbits treated by zofenopril had 0.20+/-0.12 in the common carotid and 0.06+/-0.01 in the abdominal aorta. These data indicate that ACE-inhibition with zofenopril has antiatherosclerotic and antioxidant effects in WHHL-rabbits. Our results also shows that these effects could be linked to a reduced wall-associated platelet deposition at the site of atherosclerotic lesions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Lipoprotein modification and atherosclerosis in aging.

The development of extensive atherosclerosis of major arteries of the heart, brain, and lower extremities is a particularly frequent problem in elderly individuals and is responsible for the majority of the cardiovascular morbidity and mortality in this population. Although the frequency and severity of this problem is well recognized, there has been relatively little investigation of the effects of aging on the development of atherosclerosis. Work by a number of investigators over the last 10-15 years has demonstrated that modifications of lipoproteins, resulting from oxidative stress, glycoxidation, formation of AGE, or other processes may play an important role in atherosclerosis. As described in this review, the aging process may enhance lipoprotein modification and atherosclerosis in several ways. Conditions such as hypertension, diabetes, and menopause all increase in frequency with advancing age and may contribute both directly and indirectly to lipoprotein modification and vascular injury.Additionally, in some studies of older animals and humans, there seems to be evidence for greater in vivo oxidative stress. Whether this is a specific consequence of aging and associated medical conditions, or related to differences in dietary fatty acid or antioxidant content or other lifestyle differences is currently unknown. One important consequence of this may be enhanced susceptibility of lipoproteins to oxidation. Additional study of lipoprotein modifications associated with aging is clearly needed, and may provide new insight and solutions to the common problem of atherosclerosis in the elderly.

Aging↗
PubMed1999

Ischemic threshold and myocardial stunning in the aging heart.

The aging heart appears to be more susceptible to ischemia-reperfusion injury than the adult heart. There is no evidence of an age-related difference in the threshold of myocardial ischemia and myocardial stunning. We studied the effects on mechanical, hemodynamic, and metabolic parameters of graded reduction of coronary perfusion pressure from 66 to 29 mmHg in isolated and perfused hearts from adult and senescent rats. Cardiac function was also assessed during recovery following ischemic period. In both adult and senescent hearts developed pressure and +dP/dt linearly decreased and end-diastolic pressure linearly increased with decreasing perfusion pressure. However, all mechanical parameters were more severely impaired in senescent than in adult hearts at 37 mmHg and 29 mmHg perfusion pressure, respectively (p < 0.01 vs. adult). At 29 mmHg, in both adult and senescent hearts lactate production similarly increased whereas creatine kinase leakage did not differ from controls. Developed pressure recovered more slowly in senescent than in adult hearts (p < 0.001) in the absence of cellular damage and in the presence of restoration of coronary flow. Lactate production observed at the same step of coronary perfusion pressure suggests that the ischemic threshold is similar in adult and senescent hearts. The slow recovery of myocardial contractility after the ischemic period observed in senescent hearts suggests an age-related increase in myocardial stunning.

Aging↗
PubMed1999

Pathophysiological events during pregnancy influence the development of atherosclerosis in humans.

Pathophysiological events occurring during fetal development are increasingly recognized as influencing atherosclerosis throughout childhood and adolescence. Maternal hypercholesterolemia during pregnancy markedly increases fatty streak formation in human fetal arteries. Although fetal fatty streaks partially regress under normocholesterolemic conditions, progression of atherosclerosis in children of hypercholesterolemic mothers is much faster than in children of normocholesterolemic mothers. This cannot be accounted for by conventional risk factors of atherosclerosis or inherited genetic differences. The nature of the persistent changes in the fetal arterial wall responsible for increased atherogenesis in children and the mechanisms by which maternal hypercholesterolemia induces these changes need to be investigated, because they may offer important insights into the pathogenesis of atherosclerosis and because targeted interventions in mothers during pregnancy may yield considerable long-term benefits.

Aldehydes↗
PubMed1999

Nitric oxide as a signaling molecule in the vascular system: an overview.

In retrospect, basic research in the fields of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) during the past two decades appears to have followed a logical course, beginning with the findings that NO and cGMP are vascular smooth muscle relaxants, that nitroglycerin relaxes smooth muscle by metabolism to NO, progressing to the discovery that mammalian cells synthesize NO, and finally the revelation that NO is a neurotransmitter mediating vasodilation in specialized vascular beds. A great deal of basic and clinical research on the physiologic and pathophysiologic roles of NO in cardiovascular function has been conducted since the discovery that endothelium-derived relaxing factor (EDRF) is NO. The new knowledge on NO should enable investigators in this field to develop novel and more effective therapeutic strategies for the prevention, diagnosis, and treatment of numerous cardiovascular disorders. The goal of this review was to highlight the early research that led to our current understanding of the pathophysiologic role of NO in cardiovascular medicine. Furthermore, we discussed the possible mechanism of some drugs interfering with NO signaling cascade.

Animals↗