NATHALIA JUOCYS DIAS MOREIRA

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LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina

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  • article 0 Citação(ões) na Scopus
    Enteral administration of the protease inhibitor gabexate mesilate preserves vascular function in experimental trauma/hemorrhagic shock
    (2023) MOREIRA, Nathalia J. D.; SANTOS, Fernando dos; LI, Joyce B.; ALETTI, Federico; IRIGOYEN, Maria Claudia C.; KISTLER, Erik B.
    Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration-response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10(-10) to 10(-5) M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration-response curve to the & alpha;(1) adrenergic agonist phenylephrine compared to arteries from Shock-control animals (- logEC(50): - 5.73 & PLUSMN; 0.25 vs. - 6.48 & PLUSMN; 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (- logEC(50): - 6.62 & PLUSMN; 0.21 vs. - 7.13 & PLUSMN; 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 & PLUSMN; 9 vs. 17.63 & PLUSMN; 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r(2) = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 & PLUSMN; 7.91 vs. 64.95 & PLUSMN; 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.
  • article 6 Citação(ões) na Scopus
    Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats
    (2020) MOREIRA, Nathalia Juocys Dias; SANTOS, Fernando dos; MOREIRA, Edson Dias; FARAH, Daniela; SOUZA, Leandro Eziquiel de; SILVA, Maikon Barbosa da; MORAES-SILVA, Ivana Cinthya; LINCEVICIUS, Gisele Silverio; CALDINI, Elia Garcia; IRIGOYEN, Maria Claudia Costa
    Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive+RDN (ND) or sham surgery (NS), and hypertensive+RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration-response curves to phenylephrine, sodium nitroprusside and acetylcholine (10(-10)-10(-5) M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean +/- SEM. Urinary volume was 112% higher in HD vs. HS (HS=14.94 +/- 2.5 mL; HD=31.69 +/- 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS=201 +/- 12 vs. HD=172 +/- 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS=5.8 +/- 0.7 ms(2) vs. HD=13.4 +/- 1.4 ms(2); HS=3.5 +/- 0.7 ms(2) vs. HD=10.5 +/- 1.7 ms(2), respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.