Asthma in the Brazilian Unified Health Care System: an epidemiological analysis from 2008 to 2021.

OBJECTIVE: To analyze the number of hospitalizations, the length of hospital stay, and mortality due to asthma, as well as the costs to the Unified Health Care System in Brazil between 2008 and 2021. METHODS: This was a cross-sectional epidemiological study using data from the Information Technology Department of the Brazilian Unified Health Care System. Proportional hospitalization and death rates were estimated per 100,000 population by age, microregion, and year. RESULTS: The number of hospitalizations and deaths due to asthma decreased from 2008 to 2021 (205,392 vs. 55,009 and 822 vs. 327, respectively). In addition, a between-sex difference was observed in asthma-related hospitalizations in 2008, and more men were hospitalized in 2021 (51.8%). Asthma mortality rates were similar for both sexes (50.0% each) in 2008, and a slight increase was observed in women's deaths in 2021 (52.9%). Even so, approximately one death/day and more than 55,000 hospitalizations were observed yearly, with a mean length of hospital stay of three days. Additionally, the Southeast region allocated more financial resources to asthma-related hospitalizations. CONCLUSIONS: Our results showed that the number of deaths and hospitalizations due to asthma substantially declined during the study period.

Hospitalization and mortality rates of malignant prostatic neoplasms in Brazil: A cross-sectional study from 2008 to 2018

Abstract Prostate cancer (PCa) is a highly prevalent condition among men worldwide, resulting in reduced quality of life and increased costs to health systems due to hospitalization and death. This study aimed to explore and understand the evolution of PCa in Brazil from 2008 to 2018. Data were obtained from the National Health System Department of Informatics (DATASUS) using code C61 for malignant prostatic neoplasms. We presented the hospitalization and mortality rates in a temporal-, regional- and age-dependent manner. From 2008 to 2018, a year-dependent increase in hospital admissions due to PCa was reported in Brazil, in which the Southeast region showed the highest prevalence. Men aged ≥80 and those 70-79 years old had similar hospitalization rates, followed by men aged 60-69, 50-59, 40-49 and 30-39 years old. Similarly, an increase in deaths due to PCa was reported during this period, with the highest rates seen in the Southeast. Men aged ≥80 years had higher mortality rates, followed by those aged 70-79, 60-69, 50-59, 40-49 and 30-39 years old. The results obtained indicate an age- and region-dependent increase in PCa morbidity and mortality in Brazil overtime and may contribute to the ongoing discussion on the role and future perspective of the health care system in Brazil

Asthma in the Brazilian Unified Health Care System: an epidemiological analysis from 2008 to 2021

ABSTRACT Objective: To analyze the number of hospitalizations, the length of hospital stay, and mortality due to asthma, as well as the costs to the Unified Health Care System in Brazil between 2008 and 2021. Methods: This was a cross-sectional epidemiological study using data from the Information Technology Department of the Brazilian Unified Health Care System. Proportional hospitalization and death rates were estimated per 100,000 population by age, microregion, and year. Results: The number of hospitalizations and deaths due to asthma decreased from 2008 to 2021 (205,392 vs. 55,009 and 822 vs. 327, respectively). In addition, a between-sex difference was observed in asthma-related hospitalizations in 2008, and more men were hospitalized in 2021 (51.8%). Asthma mortality rates were similar for both sexes (50.0% each) in 2008, and a slight increase was observed in women's deaths in 2021 (52.9%). Even so, approximately one death/day and more than 55,000 hospitalizations were observed yearly, with a mean length of hospital stay of three days. Additionally, the Southeast region allocated more financial resources to asthma-related hospitalizations. Conclusions: Our results showed that the number of deaths and hospitalizations due to asthma substantially declined during the study period.

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Effect of Different Extraction Methods on Anthocyanin Content in Hibiscus sabdariffa L. and their Antiplatelet and Vasorelaxant Properties.

Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 µM trolox/g of sample). HSCE significantly inhibited (100-1000 µg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca2+-activated K+ channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract.

The action of phosphodiesterase-5 inhibitors on ß-amyloid pathology and cognition in experimental Alzheimer's disease: A systematic review.

Alzheimer's disease (AD) is the most frequent cause of dementia worldwide. The etiology of AD is partially explained by the deposition of ß-amyloid in the brain. Despite extensive research on the pathogenesis of AD, the current treatments are ineffective. Here, we systematically reviewed studies that investigated whether phosphodiesterase 5 inhibitors (PDE5i) are efficient in reducing the ß-amyloid load in hippocampi and improving cognitive decline in rodent models with ß-amyloid accumulation. We identified ten original studies, which used rodent models with ß-amyloid accumulation, were treated with PDE5i, and ß-amyloid was measured in the hippocampi. PDE5i was efficient in reducing the ß-amyloid levels, except for one study that exclusively used female rodents and the treatment did not affect ß-amyloid levels. Interestingly, PDE5i prevented cognitive decline in all studies. This study supports the potential therapeutic use of PDE5i for the reduction of the ß-amyloid load in hippocampi and cognitive decline. However, we highlight the importance of conducting additional experimental studies to evaluate the PDE5i-related molecular mechanisms involved in ß-amyloid removal in male and female animals.

Evaluation of the Panbio™ COVID-19 ag rapid test at an emergency room in a hospital in São Paulo, Brazil.

BACKGROUND: The performance characteristics of the Panbio™ COVID-19 Ag test was evaluated at an emergency room setting against RT-PCR, considered the gold-standard for the detection of SARS-CoV-2, in São Paulo, Brazil. The study aimed to determine the sensitivity, specificity, Positive Percent Agreement (PPA), and Negative Percent Agreement (NPA) as compared to RT-PCR. METHODS: Specimens from 127 suspected patients were tested by both the Panbio™ COVID-19 Ag test and by RT-PCR. RESULTS: In relation to RT-PCR using Ct values ≤ 40 as the upper limit for positivity, the Panbio™ COVID-19 Ag test showed an overall sensitivity of 84.3% (95% CI 75‒93.8%) and 98.2% (95% CI 96‒98.8%) overall specificity. For Ct values ≤ 25 (n = 37), the Panbio™ COVID-19 Ag test showed 97% sensitivity. DISCUSSION: The concordance between the Panbio™ COVID-19 Ag test and RT-PCR was 97% at Ct values below 25 but decreased at higher Ct values. For disease control, it is very important to identify infected individuals who present COVID-19 symptoms and also those who are suspected of infection due to contact with infected individuals. CONCLUSION: The Panbio™ COVID-19 Ag test is suitable for use as a diagnostic test for rapid screening of patients presenting COVID-19 symptoms, or those suspected of being infected, prior to being admitted to hospital.

Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people in Brazil: a cross-sectional study.

BACKGROUND: It has been estimated that 17% of individuals aged 50 years or older suffer from addiction to legal or illegal drugs. Use of alcohol and psychoactive substances has been correlated with several diseases, e.g. psychiatric conditions and cardiovascular and sexual dysfunctions. OBJECTIVE: To discuss the Brazilian profile of mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people, over the period from 2008 to 2019. DESIGN AND SETTING: Cross-sectional study conducted among Brazilians aged 50 years or older. METHODS: Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances was assessed through data obtained from the National Health System Department of Informatics (Departamento de Informática do Sistema Único de Saúde, DATASUS). RESULTS: Decreasing and steady trends of hospitalization due to mental and behavioral disorders caused by use of alcohol among both men and women at all ages were observed. Similar trends were reported for all age ranges among men and women aged 60 years and older. In contrast, a slight increase was seen among women aged 50 to 59 years. CONCLUSION: These data are crucial for qualifying mental healthcare for older adults and elderly people and for planning mental health services.

Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people in Brazil: a cross-sectional study

ABSTRACT BACKGROUND: It has been estimated that 17% of individuals aged 50 years or older suffer from addiction to legal or illegal drugs. Use of alcohol and psychoactive substances has been correlated with several diseases, e.g. psychiatric conditions and cardiovascular and sexual dysfunctions. Objective: To discuss the Brazilian profile of mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people, over the period from 2008 to 2019. DESIGN AND SETTING: Cross-sectional study conducted among Brazilians aged 50 years or older. METHODS: Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances was assessed through data obtained from the National Health System Department of Informatics (Departamento de Informática do Sistema Único de Saúde, DATASUS). RESULTS: Decreasing and steady trends of hospitalization due to mental and behavioral disorders caused by use of alcohol among both men and women at all ages were observed. Similar trends were reported for all age ranges among men and women aged 60 years and older. In contrast, a slight increase was seen among women aged 50 to 59 years. CONCLUSION: These data are crucial for qualifying mental healthcare for older adults and elderly people and for planning mental health services.

The modulation of neuroinflammation by inducible nitric oxide synthase.

The accumulation and propagation of misfolded proteins in the brain is a pathological hallmark shared by many neurodegenerative diseases, such as the depositions of ß-amyloid and hyperphosphorylated tau proteins in Alzheimer's disease. Initial evidence shows the role of nitric oxide synthases in the development of neurodegenerative diseases. A recent, in an exciting paper (Bourgognon et al. in Proc Natl Acad Sci USA 118, 1-11, 2021. 10.1073/pnas.2009579118) it was shown that the inducible nitric oxide synthase plays an important role in promoting oxidative and nitrergic stress leading to neuroinflammation and consequently neuronal function impairments and decline in synaptic strength in mouse prion disease. In this context, we reviewed the possible mechanisms of nitric oxide synthase in the generation of neurodegenerative diseases.

Evaluation of the Panbio™ COVID-19 ag rapid test at an emergency room in a hospital in São Paulo, Brazil

Abstract Background The performance characteristics of the Panbio™ COVID-19 Ag test was evaluated at an emergency room setting against RT-PCR, considered the gold-standard for the detection of SARS-CoV-2, in São Paulo, Brazil. The study aimed to determine the sensitivity, specificity, Positive Percent Agreement (PPA), and Negative Percent Agreement (NPA) as compared to RT-PCR. Methods Specimens from 127 suspected patients were tested by both the Panbio™ COVID-19 Ag test and by RT-PCR. Results In relation to RT-PCR using Ct values ≤ 40 as the upper limit for positivity, the Panbio™ COVID-19 Ag test showed an overall sensitivity of 84.3% (95% CI 75‒93.8%) and 98.2% (95% CI 96‒98.8%) overall specificity. For Ct values ≤ 25 (n= 37), the Panbio™ COVID-19 Ag test showed 97% sensitivity. Discussion The concordance between the Panbio™ COVID-19 Ag test and RT-PCR was 97% at Ct values below 25 but decreased at higher Ct values. For disease control, it is very important to identify infected individuals who present COVID-19 symptoms and also those who are suspected of infection due to contact with infected individuals. Conclusion The Panbio™ COVID-19 Ag test is suitable for use as a diagnostic test for rapid screening of patients presenting COVID-19 symptoms, or those suspected of being infected, prior to being admitted to hospital.

Comparison of viral load between saliva and nasopharyngeal swabs for SARS-CoV2: the role of days of symptoms onset on diagnosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is highly infectious causing millions of deaths worldwide. Nasopharyngeal swabs are the primary sample of choice for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus, to decrease the exposure to potentially infected samples through the collection is a key point to reduce the risk of infection in healthcare workers. OBJECTIVES: This study aimed to evaluate the sensitivity and viral load of saliva specimens by days of symptoms onset comparing to nasopharyngeal swabs in subjects with mild symptoms. METHODS: Saliva and nasopharyngeal swabs samples were collected from São Paulo Hospital workers presenting mild symptoms, such as fever, cough, sore throat, rhinorrhea, myalgia, headaches, anosmia, ageusia, and fatigue. To understand the positivity and viral load, reverse transcription-polymerase chain reaction (RT-PCR) was performed. FINDINGS: Saliva specimens presented a sensitivity of 98.6% compared to nasopharyngeal swabs. Overall, saliva showed lower viral load compared to nasopharyngeal swabs, regarding days of symptoms onset on diagnosis, the first four days had significant changes in viral load and no significant difference was reported in the days five to nine. MAIN CONCLUSIONS: Although RT-PCR of saliva has presented a lower viral load compared to nasopharyngeal swabs, saliva specimens are a potential and reliable candidate for COVID-19 diagnosis through RT-PCR.

The role of vascular endothelial protein tyrosine phosphatase on nitric oxide synthase function in diabetes: from molecular biology to the clinic.

Endothelial nitric oxide synthase (eNOS) and receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) are one of the majors signaling pathways related to endothelial health in diabetes. Several reports have shown that the inhibition of VE-PTP can lead the nitric oxide production, although repeated studies showed that VE-PTP regulated the eNOS exclusive at Ser1177 in indirect-manner. A recent, exciting paper (Siragusa et al. in Cardiovasc Res, 2020. https://doi.org/10.1093/cvr/cvaa213 ), showing that VE-PTP regulates eNOS in a direct-manner, dephosphorylating eNOS at Tyr81 and indirect at Ser1177 and the effects of a VE-PTP inhibitor, AKB-9778, in the blood pressure from diabetic patients.

Mapping the Endothelial Cell S-Sulfhydrome Highlights the Crucial Role of Integrin Sulfhydration in Vascular Function.

BACKGROUND: In vascular endothelial cells, cysteine metabolism by the cystathionine γ lyase (CSE), generates hydrogen sulfide-related sulfane sulfur compounds (H2Sn), that exert their biological actions via cysteine S-sulfhydration of target proteins. This study set out to map the "S-sulfhydrome" (ie, the spectrum of proteins targeted by H2Sn) in human endothelial cells. METHODS: Liquid chromatography with tandem mass spectrometry was used to identify S-sulfhydrated cysteines in endothelial cell proteins and ß3 integrin intraprotein disulfide bond rearrangement. Functional studies included endothelial cell adhesion, shear stress-induced cell alignment, blood pressure measurements, and flow-induced vasodilatation in endothelial cell-specific CSE knockout mice and in a small collective of patients with endothelial dysfunction. RESULTS: Three paired sample sets were compared: (1) native human endothelial cells isolated from plaque-free mesenteric arteries (CSE activity high) and plaque-containing carotid arteries (CSE activity low); (2) cultured human endothelial cells kept under static conditions or exposed to fluid shear stress to decrease CSE expression; and (3) cultured endothelial cells exposed to shear stress to decrease CSE expression and treated with solvent or the slow-releasing H2Sn donor, SG1002. The endothelial cell "S-sulfhydrome" consisted of 3446 individual cysteine residues in 1591 proteins. The most altered family of proteins were the integrins and focusing on ß3 integrin in detail we found that S-sulfhydration affected intraprotein disulfide bond formation and was required for the maintenance of an extended-open conformation of the ß leg. ß3 integrin S-sulfhydration was required for endothelial cell mechanotransduction in vitro as well as flow-induced dilatation in murine mesenteric arteries. In cultured cells, the loss of S-sulfhydration impaired interactions between ß3 integrin and Gα13 (guanine nucleotide-binding protein subunit α 13), resulting in the constitutive activation of RhoA (ras homolog family member A) and impaired flow-induced endothelial cell realignment. In humans with atherosclerosis, endothelial function correlated with low H2Sn generation, impaired flow-induced dilatation, and failure to detect ß3 integrin S-sulfhydration, all of which were rescued after the administration of an H2Sn supplement. CONCLUSIONS: Vascular disease is associated with marked changes in the S-sulfhydration of endothelial cell proteins involved in mediating responses to flow. Short-term H2Sn supplementation improved vascular reactivity in humans highlighting the potential of interfering with this pathway to treat vascular disease.

Endothelium modulates electrical field stimulation-induced contractions of Chelonoidis carbonaria aortic rings.

The role of endothelium in the electrical-field stimulation (EFS)-induced contractions of Chelonoidis carbonaria aorta was investigated. Contractions were evaluated in the presence and absence of L-NAME (100 µM), tetrodotoxin (1 µM), phentolamine (10 and 100 µM), phenoxybenzamine (1 and 10 µM), prazosin (100 µM), idazoxan (100 µM), atropine (10 µM), D-tubocurarine (10 µM) or indomethacin (10 µM). EFS-induced contraction was also carried out in endothelium-denuded rings. EFS-induced contraction was investigated by the sandwich assay. Concentration curves to endothelin-1 (0.1-100 nM) and U46619 (0.001-100 µM) were also constructed to calculate both Emax and EC50. EFS at 16 Hz contracted Chelonoidis aorta, which was almost abolished by the endothelium removal. The addition of L-NAME increased the EFS response (2.0 ± 0.4 and 8.3 ± 1.9 mN). In L-NAME treated aortic rings, tetrodotoxin did not change the EFS-response (5.1 ± 1.8 and 4.9 ± 1.7 mN). Indomethacin, atropine and d-tubucurarine also did not affect the EFS-response. Phentolamine at 10 µM did not change the EFS-induced contraction; however, at 100 µM, reduced it (3.9 ± 1 and 1.9 ± 0.3 mN). Prazosin and idazoxan did not change EFS-induced contractions. Phenoxybenzamine at 1 µM reduced by 76% (9.6 ± 3.4 and 2.3 ± 0.8 mN) and at 10 µM by 90% the EFS response. Immunohistochemistry identified tyrosine hydroxylase in the endothelium and brain, whereas S100 protein was found only in brain. In conclusion, endothelium modulates EFS-induced contractions in Chelonoidis aortic rings and this modulation may be due to endothelium-derived catecholamines, possibly dopamine.

Autonomic dysregulation at multiple sites is implicated in age-associated underactive bladder in female mice.

AIMS: To evaluate the functional and molecular alterations of contractile and relaxant machinery in the bladder and urethra that lead to the underactive bladder (UAB) in old female mice. METHODS: Female young (3-months) and old (18-months) C57BL/6 mice were used. Urodynamic was assessed in awake and anaesthetized mice. Electrical-field stimulation (EFS) and concentration-response curves to contractile and relaxing agents in isolated bladders and urethras were performed. Messenger RNA (mRNA) expressions of muscarinic, adrenergic, and transient receptor potential vanilloid-4 (TRPV4), and of the enzymes tyrosine hydroxylase and neuronal nitric oxide synthase (nNOS) were determined. Bladder cyclic adenosine monophosphate (cAMP) levels were measured. RESULTS: Cystometry in old mice showed incapacity to produce bladder emptying. On filter paper, old mice showed reduced urinary spots. Compared to the young group, bladder contractions induced by EFS and carbachol were lower in old mice. The ß3 -adrenoceptor agonist mirabegron promoted higher bladder relaxation and elevation of cAMP levels in old mice. In old mice urethras, the α1a -adrenoceptor agonist phenylephrine produced higher contractions, but no differences were found for the NO donor sodium nitroprusside-induced relaxations. In old mice, increased mRNA expressions of ß3 - and α1a -adrenoceptors in bladder and urethra were found, respectively, whereas the muscarinic M2 and M3 receptors and ß2 -adrenoceptors did not change between groups. Reduced mRNA expressions of tyrosine hydroxylase and nNOS were found in old mouse urethras. Additionally, TRPV4 expression was reduced in bladder urothelium from old mice. CONCLUSION: Age-associated mouse UAB is the result of autonomic dysfunction at multiple levels leading to the less sensitive and overrelaxed bladder, along with urethral hypercontractility.

Pharmacological and transcriptomic characterization of the nitric oxide pathway in aortic rings isolated from the tortoise Chelonoidis carbonaria.

In this study the nitric oxide (NO)-soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) pathway was characterized in tortoise Chelonoidis carbonaria aorta. Concentration response curves (CCR) to ATP, ADP, AMP, adenosine and histamine were performed in the presence and absence of L-NAME in aorta pre-contracted with ACh (3 µM). CCR to SNP, BAY 41-2272 (sGC stimulator), BAY 60-2770 (sGC activator) and tadalafil (PDE-5 inhibitor) were constructed in the presence and absence of ODQ (10 µM). ATP (pEC50 6.1 ±â€¯0.1), ADP (pEC50 6.0 ±â€¯0.2), AMP (pEC50 6.8 ±â€¯0.1) and histamine (pEC50 6.8 ±â€¯0.12) relaxed Chelonoidis aorta and the addition of L-NAME reduced their efficacy (p < .05). Adenosine effects (pEC50 6.6 ±â€¯0.1) were not changed in the presence of L-NAME. SNP (pEC50 7.5 ±â€¯0.7; Emax 102.2 ±â€¯2.5%), BAY 41-2272 (pEC50 7.3 ±â€¯0.2; Emax 130.3 ±â€¯10.2%), BAY 60-2770 (pEC50 11.4 ±â€¯0.1; Emax 130.3 ±â€¯6.5%) and tadalafil (pEC50 6.7 ±â€¯0.3; Emax 121.3 ±â€¯15.3%) relaxed Chelonoidis aorta. The addition of ODQ reduced the SNP and tadalafil maximum response (p < .05) and promoted 63 fold right shift on BAY 41-2272 curve. In contrast, no alteration was observed on BAY 60-2770 response. Transcriptomic analysis for eNOS and sGC were found in aorta and brain libraries with high homology when compared with human transcripts. The NO-sGC-PDE-5 is functionally present in Chelonoidis aorta with a functional and genomic similarity to mammalian vessels. Unlike most of mammalian vessels, ACh did not cause endothelium-dependent relaxation in Chelonoidis carbonaria aortic rings.

Electrical field-induced contractions on Crotalus durissus terrificus and Bothrops jararaca aortae are caused by endothelium-derived catecholamine.

Endothelium is the main source of catecholamine release in the electrical-field stimulation (EFS)-induced aortic contractions of the non- venomous snake Panterophis guttatus. However, adrenergic vasomotor control in venomous snakes such as Crotalus durissus terrificus and Bothrops jararaca has not yet been investigated. Crotalus and Bothrops aortic rings were mounted in an organ bath system. EFS-induced aortae contractions were performed in the presence and absence of guanethidine (30 µM), phentolamine (10 µM) or tetrodotoxin (1 µM). Frequency-induced contractions were also performed in aortae with endothelium removed. Immunohistochemical localization of both tyrosine hydroxylase (TH) and S-100 protein in snake aortic rings and brains, as well as in human tissue (paraganglioma tumour) were carried out. EFS (4 to 16 Hz) induced frequency-dependent aortic contractions in both Crotalus and Bothrops. The EFS-induced contractions were significantly reduced in the presence of either guanethidine or phentolamine in both snakes (p<0.05), whereas tetrodotoxin had no effect in either. Removal of the endothelium abolished the EFS-induced contractions in both snakes aortae (p<0.05). Immunohistochemistry revealed TH localization in endothelium of both snake aortae and human vessels. Nerve fibers were not observed in either snake aortae. In contrast, both TH and S100 protein were observed in snake brains and human tissue. Vascular endothelium is the main source of catecholamine release in EFS-induced contractions in Crotalus and Bothrops aortae. Human endothelial cells also expressed TH, indicating that endothelium- derived catecholamines possibly occur in mammalian vessels.