Nitric oxide regulates angiotensin-I converting enzyme under static conditions but not under shear stress

Abstract

Mechanical forces including pressure and shear stress play an important role in vascular homeostasis via the control of the production and release of a variety of vasoactive factors. An increase in vascular shear stress is accompanied by nitric oxide (NO) release and NO synthase activation. Previously, we have demonstrated that shear stress induces angiotensin-I converting enzyme (ACE) down-regulation in vivo and in vitro. In the present study, we determined whether NO participates in the shear stress-induced ACE suppression response. Rabbit aortic endothelial cells were evaluated using the NO synthase inhibitor L-NAME, and two NO donors, diethylamine NONOate (DEA/NO) and sodium nitroprusside (SNP). Under static conditions, incubation of endothelial cells with 1 mM L-NAME for 18 h increased ACE activity by 27% (from 1.000 ± 0.090 to 1.272 ± 0.182) while DEA/NO and SNP (0.1, 0.5 and 1 mM) caused no change in ACE activity. Interestingly, ACE activity was down-regulated similarly in the presence or absence of L-NAME (∆ (0 mM) = 0.26 ± 0.055, ∆ (0.1 mM) = 0.21 ± 0.22, ∆ (1 mM) = 0.36 ± 0.13) upon 18 h shear stress activation (from static to 15 dyn/cm 2 ). Taken together, these results indicate that NO can participate in the maintenance of basal ACE levels in the static condition but NO is not associated with the shear stress-induced inactivation of ACE. Correspondence

ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser1270

“…ACE promoter activity remained unchanged by the SS-conditioned medium (Figure 4B and 5A) suggesting that SS-induced ACE decreased expression is not secondary to the release of factor(s) stimulated by the mechanical force, which is in agreement with previous data from our group showing that NO does not modulate ACE under SS condition [13].…”

“…Indeed, we provided evidence that SS-induced ACE downregulation requires the integrity of two alternative cis-acting elements, Barbie and GAGA-boxes [11]. In addition, we and others have showed that although nitric oxide (NO), a potent vasodilator, antioxidant and anti-inflamatory mediator synthesized and released by SS, influences basal ACE levels in the static conditions [12], it is not associated with the SS-induced ACE gene suppression [13].…”

“…The sustained exposure of ECs to laminar shear stress is accompanied by the release of several antiatherogenic factors, including prostacyclin (PGI2), transforming growth factor-β (TGF- β) and nitric oxide (NO) [31]. We have previously demonstrated that NO is not involved in ACE downregulation by SS, although NO can regulate ACE under basal static conditions [12], [13]. Here, we used shear-conditioned medium and observed no modification on ACE promoter activity under the conditions tested.…”

Efeito agudo de uma sessão de CrossFit® sobre as variáveis hemodinâmicas e a percepção de esforço de adultos treinados

“…As variações hemodinâmicas produzidas por uma sessão de CrossFit® podem favorecer a saúde do sistema cardiovascular, pois a força tangencial exercida pelo contato entre o sangue e as paredes arteriais, conhecida como shear stress, parece atuar sobre o controle da produção e a liberação de diversos fatores vasoativos, como o óxido nítrico, a prostraciclina, o fator de crescimento derivado de plaquetas (PDGF), e o fator de crescimento de fibroblastos (FGF) (29).…”

Protective action figurations for superoxide dismutase - chondroitin sulfate - catalase bienzyme conjugate after its medicative administration in endotoxin shock

“…По литературным данным отмечалось возможное влияние экзогенной СОД на эндогенные защитные антиоксидантные системы [16], NO-независимый путь стимуляции гуанилилциклазы, способствующий снижению размера инфаркта миокарда у крыс [17], появление АФК на поздних стадиях развития ангиотензин-II -индуцированной гипертонии [18]. Было обнаружено, что имеется влияние NO на базальный уровень ангиотензин-превращающего фермента (АПФ) в статичных условиях, но нет такой связи с супрессией гена АПФ, вызванной напряжением сдвига (shear stress) [19]. АПФ оказывается механосенсором регуляции своей активности в ответ на напряжение сдвига [20,21].…”