ALTERAÇÃO DE PARÂMETROS RELACIONADOS AO RISCO CARDIOVASCULAR EM ADOLESCENTES OBESOS

Introdução: A obesidade juvenil é considerada um problema de saúde pública e o aumento de sobrepeso e obesidade nesta fase está associado a complicações metabólicas e cardiovasculares na idade adulta1. Objetivo: Identificar alterações nos parâmetros antropométricos e bioquímicas em adolescentes obesos. Metodologia: Adolescentes (14-18 anos), de ambos os sexos, matriculados em escolas de Ensino Médio de Barra do Garças – MT foram divididos em grupos experimentais de acordo com o Índice de Massa corporal (IMC): eutróficos (IMC ˃18 e ˂25) e obesos (IMC˂25)2. O IMC, circunferência abdominal, porcentagem de gordura corporal, pressão arterial, dosagens de colesterol total, triglicérides e glicemia foram avaliados em ambos grupos. Diferenças estatísticas foram calculadas através do teste T Student, (p˂0,05). Resultados e discussões: Foram avaliados 89 adolescentes, sendo 74 eutróficos e 15 obesos. Os adolescentes obesos apresentaram aumento dos valores de pressão sistólica [(mmHg) 126 ± 3,7 vs. 116±1,7], circunferência abdominal [(cm) 87± 1,9 vs. 72 ± 0,6], porcentagem de gordura corporal [(%) 27±1,8 vs. 18 ± 0,7], IMC (27,1±0,7 vs. 21.0±0,2), quando comparados ao grupo eutrófico. Adicionalmente, os adolescentes obesos apresentaram aumento nos índices de colesterol total [(mg/dL) 160 ± 7,4 vs. 140 ± 3,8], triglicérides [(mg/dL) 106,6±14,4 vs. 64,0±3,8], se comparados ao grupo eutrófico. Tanto a pressão diastólica quanto os níveis glicêmicos não apresentaram alteração entre os grupos. Conclusões: As alterações de parâmetros antropométricos e bioquímicos observados em adolescentes obesos demonstram que fatores de risco para doenças cardiovasculares estão alterados nessa população jovem, favorecendo o surgimento precoce de doenças crônicas como Diabetes Mellitus e da hipertensão arterial

Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy. A Non-systematic Review of Clinical Presentation, Potential Effects of Physiological Adaptations in Pregnancy, and Placental Vascular Alterations

In December 2019, the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) rapidly spread to become a pandemic. To date, increasing evidence has described the potential negative impact of SARS-CoV-2 infection on pregnant women. Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not entirely understood, there is emerging evidence that it causes a severe systemic inflammatory response associated with vascular alterations that could be of special interest considering some physiological changes in pregnancy. Additionally, these alterations may affect the physiology of the placenta and are associated with pregnancy complications and abnormal histologic findings. On the other hand, data about the vaccine against SARS-CoV-2 are limited, but the risks of administering COVID-19 vaccines during pregnancy appear to be minimal. This review summarizes the current literature on SARSCoV2 virus infection, the development of COVID-19 and its relationship with physiological changes, and angiotensin-converting enzyme 2 (ACE2) function during pregnancy. We have particularly emphasized evidence coming from Latin American countries.Fil: Ayala Ramírez, Paola. Pontificia Universidad Javeriana; ColombiaFil: González, Marcelo. Universidad de Concepción; ChileFil: Escudero, Carlos. Universidad del Bio Bio; ChileFil: Quintero Arciniegas, Laura. Pontificia Universidad Javeriana; ColombiaFil: Giachini, Fernanda R.. Universidade Federal de Goiás; Brasil. Universidade Federal do Mato Grosso do Sul; BrasilFil: Alves de Freitas, Raiany. Universidade Federal de Goiás; BrasilFil: Damiano, Alicia Ermelinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: García-Robles, Reggie. Pontificia Universidad Javeriana; Colombi

STIM1/Orai1 contributes to sex differences in vascular responses to calcium in spontaneously hypertensive rats. Clin. Sci. (Lond

Sex differences in Ca 2 + -dependent signalling and homoeostasis in the vasculature of hypertensive rats are well characterized. However, sex-related differences in SOCE (store-operated Ca 2 + entry) have been minimally investigated. We hypothesized that vascular protection in females, compared with males, reflects decreased Ca 2 + mobilization due to diminished activation of Orai1/STIM1 (stromal interaction molecule 1). In addition, we investigated whether ovariectomy in females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive rats) and WKY (Wistar-Kyoto) rats and from OVX (ovariectomized) or sham female SHRSP and WKY rats were used to functionally evaluate Ca 2 + influx-induced contractions. Compared with females, aorta from male SHRSP displayed: (i) increased contraction during the Ca 2 + -loading period; (ii) similar transient contraction during Ca 2 + release from the intracellular stores; (iii) increased activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with neutralizing antibodies, which reversed the sex differences in contraction during the Ca 2 + -loading period; and (iv) increased expression of STIM1 and Orai1. Additionally, we found that aortas from OVX-SHRSP showed increased contraction during the Ca 2 + -loading period and increased Orai1 expression, but no changes in the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These findings suggest that augmented activation of STIM1/Orai1 in aortas from male SHRSP represents a mechanism that contributes to sex-related impaired control of intracellular Ca 2 + levels. Furthermore, female sex hormones may negatively modulate the STIM/Orai1 pathway, contributing to vascular protection observed in female rats

Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats

Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity.National Institutes of Health (HL71138, HL74167)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)INCT Obesity and DiabetesConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq

Cigarette Smoking and Erectile Dysfunction: Focus on NO Bioavailability and ROS Generation

Introduction.  Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem, which seriously affects the quality of life of patients and their partners, ED becomes increasingly prevalent with age and chronic smoking is a major risk factor in the development of ED. Aim.  To review available evidence concerning the effects of cigarette smoking on vascular changes associated with decreased nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS) generation. Methods.  We examined epidemiological and clinical data linking cigarette smoking and ED, and the effects of smoking on vascular NO bioavailability and ROS generation. Main Outcome Measures.  There are strong parallels between smoking and ED and considerable evidence supporting the concept that smoking-related ED is associated with reduced bioavailability of NO because of increased ROS. Results.  Cigarette smoking-induced ED in human and animal models is associated with impaired arterial flow to the penis or acute vasospasm of the penile arteries. Long-term smoking produces detrimental effects on the vascular endothelium and peripheral nerves and also causes ultrastructural damage to the corporal tissue, all considered to play a role in chronic smoking-induced ED. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium-dependent smooth muscle relaxation or more specifically by affecting NO production via increased ROS generation. Whether nicotine or other products of cigarette smoke mediate all effects related to vascular damage is still unknown. Conclusions.  Smoking prevention represents an important approach for reducing the risk of ED. The characterization of the components of cigarette smoke leading to ED and the mechanisms by which these components alter signaling pathways activated in erectile responses are necessary for a complete comprehension of cigarette smoking-associated ED. Tostes RS, Carneiro FS, Lee AJ, Giachini FRC, Leite R, Osawa Y, and Clinton Webb R. Cigarette smoking and erectile dysfunction: Focus on NO bioavailability and ROS generation. J Sex Med 2008;5:1284–1295.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75024/1/j.1743-6109.2008.00804.x.pd

STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?

Sex-associated differences in hypertension have been observed repeatedly in epidemiological studies; however, the mechanisms conferring vascular protection to females are not totally elucidated. Sex-related differences in intracellular Ca(2+) handling or, more specifically, in mechanisms that regulate Ca(2+) entry into vascular smooth muscle cells have been identified as players in sex-related differences in hypertension-associated vascular dysfunction. Recently, new signalling components that regulate Ca(2+) influx, in conditions of intracellular store depletion, were identified: STIM1 (stromal interaction molecule 1), which works as an intracellular Ca(2+) sensor; and Orai1, which is a component of the CRAC (Ca(2+) release-activated Ca(2+)) channels. Together, these proteins reconstitute store-operated Ca(2+) channel function. Disturbances in STIM1/Orai1 signalling have been implicated in pathophysiological conditions, including hypertension. In the present article, we analyse evidence for sex-related differences in Ca(2+) handling and propose a new hypothesis where sex-related differences in STIM/Orai signalling may contribute to hypertension-associated vascular differences between male and female subjects.American Heart Association[2250383

PYK2/PDZ-RhoGEF Links Ca(2+) Signaling to RhoA

Objective-Ras homolog gene family member A (RhoA)/Rho-kinase-mediated Ca(2+) sensitization is a critical component of constrictor responses. The present study investigates how angiotensin II activates RhoA. Methods and Results-Adenoviral vectors were used to manipulate the expression of regulator of G protein signaling (RGS) domain containing Rho-specific guanine exchange factors (RhoGEFs) and proline-rich tyrosine kinase 2 (PYK2), a nonreceptor tyrosine kinase, in primary rat vascular smooth muscle cells. As an evidence of RhoA activation, RhoA translocation and MYPT1 (the regulatory subunit of myosin light chain phosphatase) phosphorylation were analyzed by Western blot. Results showed that overexpression of PDZ-RhoGEF, but not p115-RhoGEF or leukemia-associated RhoGEF (LARG), enhanced RhoA activation by angiotensin II. Knockdown of PDZ-RhoGEF decreased RhoA activation by angiotensin II. PDZ-RhoGEF was phosphorylated and activated by PYK2 in vitro, and knockdown of PDZ-RhoGEF reduced RhoA activation by constitutively active PYK2, indicating that PDZ-RhoGEF links PYK2 to RhoA. Knockdown of PYK2 or PDZ-RhoGEF markedly decreased RhoA activation by A23187, a Ca(2+) ionophore, demonstrating that PYK2/PDZ-RhoGEF couples RhoA activation to Ca(2+). Conclusions-PYK2 and PDZ-RhoGEF are necessary for angiotensin II-induced RhoA activation and for Ca(2+) signaling to RhoA. (Arterioscler Thromb Vasc Biol. 2009;29:1657-1663.)National Institutes of Health (NIH)[HL-71138]National Institutes of Health (NIH)[HL-74167