Redox stress defines the small artery vasculopathy of hypertension: how do we bridge the bench-to-bedside gap?

Although convincing experimental evidence demonstrates the importance of vascular reactive oxygen and nitrogen species (RONS), oxidative stress, and perturbed redox signaling as causative processes in the vasculopathy of hypertension, this has not translated to the clinic. We discuss this bench-to-bedside disparity and the urgency to progress vascular redox pathobiology from experimental models to patients by studying disease-relevant human tissues. It is only through such approaches that the unambiguous role of vascular redox stress will be defined so that mechanism-based therapies in a personalized and precise manner can be developed to prevent, slow, or reverse progression of small-vessel disorders and consequent hypertension

c-Src inhibition improves cardiovascular function but not remodeling or fibrosis in Ang II-induced hypertension

c-Src plays an important role in angiotensin II (Ang II) signaling. Whether this member of the Src family kinases is involved in the development of Ang II–induced hypertension and associated cardiovascular damage in vivo remains unknown. Here, we studied Ang II–infused (400 ng/kg/min) mice in which c-Src was partially deleted (c-Src+/−) and in wild-type (WT, c-Src+/+) mice treated with a c-Src inhibitor (CGP077675; 25 mg/kg/d). Ang II increased blood pressure and induced endothelial dysfunction in WT mice, responses that were ameliorated in c-Src+/− and CGP077675-treated mice. Vascular wall thickness and cross-sectional area were similarly increased by Ang II in WT and c-Src+/− mice. CGP077675 further increased cross-sectional area in hypertensive mice. Cardiac dysfunction (ejection fraction and fractional shortening) in Ang II–infused WT mice was normalized in c-Src+/− mice. Increased oxidative stress (plasma thiobarbituric acid–reactive substances, hydrogen peroxide, and vascular superoxide generation) in Ang II–infused WT mice was attenuated in c-Src–deficient and CGP077675-treated mice. Hyperactivation of vascular c-Src, ERK1/2 (extracellular signal–regulated kinase 1/2), and JNK (c-Jun N-terminal kinase) in hypertensive mice was normalized in CGP077675-treated and c-Src+/− mice. Vascular fibronectin was increased by Ang II in all groups and further augmented by CGP077675. Cardiac fibrosis and inflammation induced by Ang II were amplified in c-Src+/− and CGP-treated mice. Our data indicate that although c-Src downregulation attenuates development of hypertension, improves endothelial and cardiac function, reduces oxidative stress, and normalizes vascular signaling, it has little beneficial effect on fibrosis. These findings suggest a divergent role for c-Src in Ang II–dependent hypertension, where c-Src may be more important in regulating redox-sensitive cardiac and vascular function than fibrosis and remodeling

Bifenthrin Baseline Susceptibility and Evaluation of Simulated Aerial Applications in \u3ci\u3eStriacosta albicosta\u3c/i\u3e (Lepidoptera: Noctuidae)

Striacosta albicosta (Smith) is a maize pest that has recently expanded its geographical range into the eastern United States and southeastern Canada. Aerial application of pyrethroids, such as bifenthrin, has been a major practice adopted to manage this pest. Reports of field failure of pyrethroids have increased since 2013. Striacosta albicosta populations were collected in 2016 and 2017 from maize fields in Nebraska, Kansas, and Canada and screened with bifenthrin active ingredient in larval contact dose-response bioassays. Resistance ratios estimated were generally low in 2016 (1.04- to 1.32-fold) with the highest LC50 in North Platte, NE (66.10 ng/cm2) and lowest in Scottsbluff, NE (50.10 ng/cm2). In 2017, O’Neill, NE showed the highest LC50 (100.66 ng/cm2) and Delhi, Canada exhibited the lowest (6.33 ng/cm2), resulting in a resistance ratio variation of 6.02- to 15.90-fold. Implications of bifenthrin resistance levels were further investigated by aerial application simulations. Experiments were conducted with a spray chamber where representative S. albicosta populations were exposed to labeled rates of a commercial bifenthrin formulation. Experiments resulted in 100% mortality for all populations, instars, insecticide rates, and carrier volumes, suggesting that levels of resistance estimated for bifenthrin active ingredient did not seem to impact the efficacy of the correspondent commercial product under controlled conditions. Results obtained from this research indicate that control failures reported in Nebraska could be associated with factors other than insecticide resistance, such as issues with the application technique, environmental conditions during and/or after application, or the insect’s natural behavior. Data generated will assist future S. albicosta resistance management programs

Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1–7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes’ diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes’ diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1–7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation

Life-History Parameters of Striacosta albicosta (Lepidoptera: Noctuidae) Under Laboratory Conditions

Striacosta albicosta (Smith) is a key pest of maize and dry beans in North America. It has expanded its distribution from the western Great Plains of the United States to the Great Lakes region in the United States and Canada. There has been limited research on the baseline biological aspects of this insect under controlled conditions. The objective of this study was to detail the biological parameters of S. albicosta feeding on an artificial diet under laboratory conditions. Overall survival from neonate to adult at 26.6 ± 1°C was 36.72% and the total developmental time was approximately 110 d. Survival of the egg, larval, prepupal, and pupal stages were 75.71, 98.50, 51.78, and 95.10%, respectively. Average duration of the egg, larval, prepupal, and pupal stages was 4.64, 28.20, 41.50, and 25.91 d, respectively. During the larval stage, 92.50% of larvae developed through seven instars and the remaining through six instars. Larvae that developed through six and seven instars exhibited a mean growth ratio of 1.60 and 1.47, respectively; however, there was no difference in pupal weight. Eggs laid by field-mated moths showed a fertility of 75.71%, compared with 4.18% from laboratory-reared moths. These data suggest that S. albicosta develop primarily through seven instars and the most vulnerable developmental stage is the prepupa. Laboratory conditions strongly affected fertility success. Information presented here greatly expands our understanding of S. albicosta biology, which can be used to improve the efficiency of laboratory bioassays and management techniques for this critical crop pest

Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain

We demonstrated a role for the Mg2 + transporter TRPM7, a bifunctional protein with channel and α-kinase domains, in aldosterone signaling. Molecular mechanisms underlying this are elusive. Here we investigated the function of TRPM7 and its α-kinase domain on Mg2 + and pro-inflammatory signaling by aldosterone. Kidney cells (HEK-293) expressing wild-type human TRPM7 (WThTRPM7) or constructs in which the α-kinase domain was deleted (ΔKinase) or rendered inactive with a point mutation in the ATP binding site of the α-kinase domain (K1648R) were studied. Aldosterone rapidly increased [Mg2 +]i and stimulated NADPH oxidase-derived generation of reactive oxygen species (ROS) in WT hTRPM7 and TRPM7 kinase dead mutant cells. Translocation of annexin-1 and calpain-II and spectrin cleavage (calpain target) were increased by aldosterone in WT hTRPM7 cells but not in α-kinase-deficient cells. Aldosterone stimulated phosphorylation of MAP kinases and increased expression of pro-inflammatory mediators ICAM-1, Cox-2 and PAI-1 in Δkinase and K1648R cells, effects that were inhibited by eplerenone (mineralocorticoid receptor (MR) blocker). 2-APB, a TRPM7 channel inhibitor, abrogated aldosterone-induced Mg2 + responses in WT hTRPM7 and mutant cells. In 2-APB-treated ΔKinase and K1648R cells, aldosterone-stimulated inflammatory responses were unchanged. These data indicate that aldosterone stimulates Mg2 + influx and ROS production in a TRPM7-sensitive, kinase-insensitive manner, whereas activation of annexin-1 requires the TRPM7 kinase domain. Moreover TRPM7 α-kinase modulates inflammatory signaling by aldosterone in a TRPM7 channel/Mg2 +-independent manner. Our findings identify novel mechanisms for non-genomic actions of aldosterone involving differential signaling through MR-activated TRPM7 channel and α-kinase

Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress

Vascular inflammatory responses play an important role in several cardiovascular diseases. Of the many pro-inflammatory vasoactive factors implicated in this process, is aldosterone, an important mediator of vascular oxidative stress. Statins, such as atorvastatin, are cholesterol-lowering drugs that have pleiotropic actions, including anti-oxidant properties independently of their cholesterol-lowering effect. This study investigated whether atorvastatin prevents aldosterone-induced VSMC inflammation by reducing reactive oxygen species (ROS) production. Vascular smooth muscle cells (VSMC) from WKY rats were treated with 1 μM atorvastatin for 60 min or for 72 h prior to aldosterone (100 nM) stimulation. Atorvastatin inhibited Rac1/2 and p47phox translocation from the cytosol to the membrane, as well as reduced aldosterone-induced ROS production. Atorvastatin also attenuated aldosterone-induced vascular inflammation and macrophage adhesion to VSMC. Similarly EHT1864, a Rac1/2 inhibitor, and tiron, ROS scavenger, reduced macrophage adhesion. Through its inhibitory effects on Rac1/2 activation and ROS production, atorvastatin reduces vascular ROS generation and inhibits VSMC inflammation. Our data suggest that in conditions associated with aldosterone-induced vascular damage, statins may have vasoprotective effects by inhibiting oxidative stress and inflammation

Movement of \u3ci\u3eStriacosta albicosta\u3c/i\u3e (Smith) (Lepidoptera: Noctuidae) Larvae on Transgenic \u3ci\u3eBt\u3c/i\u3e and Non-\u3ci\u3eBt\u3c/i\u3e Maize

Exposure of lepidopteran pests to Bacillus thuringiensis (Bt) proteins has been shown to affect the behavior of larvae, including increased movement and avoidance of Bt-expressing plants or diet. Therefore, we hypothesized that the behavior of western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), an important pest of maize, could be affected when exposed to Bt plants. To test this hypothesis, we conducted a series of artificial arena and on-plant experiments to determine S. albicosta neonate behavior when exposed to Bt and non-Bt plant tissue. Video tracking experiments presented neonate larvae with the choice of Bt or non-Bt pollen in a Petri dish for 15 min while being video recorded for analysis with EthoVision software. This study showed an increase in mean velocity and total time spent moving for larvae in the presence of Cry1F vs. non-Bt when compared with Vip3A vs. non-Bt or Cry1F vs. Vip3A. However, there was no difference in total distance moved or time spent in the food zone for all scenarios. Maize tissue choice experiments allowed neonatal larvae the choice of feeding on Bt or non-Bt tassel or leaves for 9 h in Petri dish arenas. This experiment showed that larvae preferred tassel tissue over leaves but did not indicate that larvae could distinguish between Bt and non-Bt tissue. In contrast, on-plant experiments (including a whole plant neonate dispersal study under controlled conditions and an in-field silking behavior experiment) indicated that the presence of Cry1F and Vip3A Bt toxins increased plant abandonment, suggesting that larvae are able to detect and avoid Bt toxins. The discrepancy of these results is likely due to the on-plant studies providing more field-realistic environmental conditions and a longer duration of exposure to Bt toxins for the behavioral experiments. Our results represent the first steps in understanding the complex behavior of S. albicosta when exposed to Bt plants. A better understanding of the response of larvae when exposed to Bt traits can aid in the management of this pest, particularly for the design of resistance management strategies and refuge design

Immature development of Spodoptera dolichos (Fabricius) (Lepidoptera: noctuidae).

We provide detailed temporal and morphological parameters of the immature stages of Spodoptera dolichos (Fabricius) larvae fed on artificial diet under controlled conditions (25?±?1°C, 70?±?10% RH, and 14 h photophase). The viability of the egg, larval, pupal, and prepupal stages was 97.5%, 97.0%, 93.1%, and 98.9%, respectively. The average duration of the egg, larval, prepupal, and pupal stages was 5.0, 23.4, 3.2, and 21.5 days, respectively. Females took longer at the larval stage than males, with 10.5% of them having seven instars. The growth rate of female larvae that developed through six and seven instars was 1.72 and 1.54, respectively. Female pupae were significantly larger, exhibiting slower development than males

Efeito do tamanho e de múltiplos casais sobre o potencial reprodutivo de Spodoptera eridania (Stoll, 1782) (Lepidoptera: Noctuidae).

Entre os lepidópteros de importância agrícola, Spodoptera eridania (Stoll, 1782) tem despertado atenção por atingir níveis de dano econômico em culturas de importância como algodão e soja. Entretanto, existem poucos estudos detalhados de biologia, especialmente relacionados a aspectos reprodutivos. Visando determinar a capacidade máxima reprodutiva desta espécie avaliou-se o efeito do tamanho, empregando como parâmetro o peso pupal, e o número de casais por gaiola (um e três) sobre o número de cópulas, fecundidade e fertilidade. Os experimentos foram conduzidos em sala climatizada (25 ± 1ºC, 70 ± 10% UR e fotofase de 14 horas) com observações diárias. Adultos, emergidos no mesmo dia, classificados de acordo com a massa pupal, como pequenos, médios e grandes foram dispostos em gaiolas plásticas, (10 x 15cm), alimentados com dieta artificial e água estéril. Foram formadas 15 gaiolas com um casal cada, todos de tamanho médio, cinco gaiolas com 3 casais de tamanho pequeno e médio e 4 com três casais de tamanho grande. O número médio de cópulas dos casais de tamanho médio mantidos individualmente (1,13) foi significativamente menor do que o dos insetos pequenos (2,58), médios (2,47) e grandes (2,33),mantidos a três por gaiola. A fecundidade média dos casais individuais (1.398,00) também foi significativamente menor que a dos mantidos a três por gaiola, tanto de tamanho pequeno (1.709,07), médio (2.044,27) e grande (2.469,92). Entre estes últimos observou-se efeito positivo entre o tamanho da pupa e a fecundidade, com diferenças significativas entre todos os tamanhos. A fertilidade média dos casais individuais (67,45) foi muito inferior a observada para os casais pequenos (97,32%), médios (96,43%) e grandes (98,91%), mantidos a três por gaiola. Estes resultados indicam que em estudos que estimam o potencial reprodutivo devem ser utilizados pelo menos três casais por gaiola e que sejam descritos os pesos das pupas que originaram os adultos