Marcelo Mendonça Mota

Structural relationships and vasorelaxant activity of monoterpenes

Background and purpose of the studyThe hypotensive activity of the essential oil of Mentha x villosa and its main constituent, the monoterpene rotundifolone, have been reported. Therefore, our objective was to evaluate the vasorelaxant effect of monoterpenes found in medicinal plants and establish the structure-activity relationship of rotundifolone and its structural analogues on the rat superior mesenteric artery.MethodsContractions of the vessels were induced with 10 μM of phenylephine (Phe) in rings with endothelium. During the tonic phase of the contraction, the monoterpenes (10-8 - 10-3, cumulatively) were added to the organ bath. The extent of relaxation was expressed as the percentage of Phe-induced contraction.ResultsThe results from the present study showed that both oxygenated terpenes (rotundifolone, (+)-limonene epoxide, pulegone epoxide, carvone epoxide, and (+)-pulegone) and non-oxygenated terpene ((+)-limonene) exhibit relaxation activity. The absence of an oxygenated molecular structure was not a critical requirement for the molecule to be bioactive. Also it was found that the position of ketone and epoxide groups in the monoterpene structures influence the vasorelaxant potency and efficacy.Major conclusionThe results suggest that the presence of functional groups in the chemical structure of rotundifolone is not essential for its vasorelaxant activity.

Resistance exercise acutely enhances mesenteric artery insulin-induced relaxation in healthy rats.

AIMS We evaluated the mechanisms involved in insulin-induced vasodilatation after acute resistance exercise in healthy rats. MAIN METHODS Wistar rats were divided into 3 groups: control (CT), electrically stimulated (ES) and resistance exercise (RE). Immediately after acute RE (15 sets with 10 repetitions at 70% of maximal intensity), the animals were sacrificed and rings of mesenteric artery were mounted in an isometric system. After this, concentration-response curves to insulin were performed in control condition and in the presence of LY294002 (PI3K inhibitor), L-NAME (NOS inhibitor), L-NAME+TEA (K(+) channels inhibitor), LY294002+BQ123 (ET-A antagonist) or ouabain (Na(+)/K(+) ATPase inhibitor). KEY FINDINGS Acute RE increased insulin-induced vasorelaxation as compared to control (CT: Rmax=7.3 ± 0.4% and RE: Rmax=15.8 ± 0.8%; p<0.001). NOS inhibition reduced (p<0.001) this vasorelaxation from both groups (CT: Rmax=2.0 ± 0.3%, and RE: Rmax=-1.2 ± 0.1%), while PI3K inhibition abolished the vasorelaxation in CT (Rmax=-0.1±0.3%, p<0.001), and caused vasoconstriction in RE (Rmax=-6.5 ± 0.6%). That insulin-induced vasoconstriction on PI3K inhibition was abolished (p<0.001) by the ET-A antagonist (Rmax=2.9 ± 0.4%). Additionally, acute RE enhanced (p<0.001) the functional activity of the ouabain-sensitive Na(+)/K(+) ATPase activity (Rmax=10.7 ± 0.4%) and of the K(+) channels (Rmax=-6.1±0.5%; p<0.001) in the insulin-induced vasorelaxation as compared to CT. SIGNIFICANCE Such results suggest that acute RE promotes enhanced insulin-induced vasodilatation, which could act as a fine tuning to vascular tone.

Endothelium adjustments to acute resistance exercise are intensity-dependent in healthy animals

AIMS We evaluated the acute effects of different intensities of resistance exercise over endothelium-dependent vasodilatation, eNOSser1177 phosphorylation level and endothelial production of NO in superior mesenteric artery of healthy rats. MAIN METHODS Groups: control (Ct), resistance exercise in the intensities of 30% (Ex30%), 50% (Ex50%) and 70% (Ex70%) of the maximal load established by the maximal repetition test (1RM). Exercise protocol: 15 sets of 10 repetitions. The rings of mesenteric artery were mounted in an isometric system or were prepared for further implementation of Western blot and DAF-FM techniques. KEY FINDINGS The maximal response of the relaxation induced by insulin was not altered in the animals of the Ex30% group when compared to the Ct group. However, the animals of the Ex50% and Ex70% groups presented an increase in this response when compared to the Ct group. The eNOSser1177 phosphorylation levels showed an increase in Ex50% and Ex70% groups when compared to the Ct (1.6-fold and 3.3-fold, respectively). In the endothelial production of NO, it was observed that the Ex30% group did not show alteration in the NO production when compared to the Ct group. On the other hand, the animals exercised in the Ex50% and Ex70% groups showed increase in the NO synthesis when compared to the animals in the Ct group. SIGNIFICANCE Our results suggest that the magnitude of these vascular endothelium adjustments is strongly related to the increase of the resistance exercise intensity from the intensity of 50% of 1 RM.

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

Background Resistance exercise effects on cardiovascular parameters are not consistent. Objectives The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Conclusions Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

Effects of one resistance exercise session on vascular smooth muscle of hypertensive rats.

Background Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Methods Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Results Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

Valor nutritivo da silagem de maniçoba ("Manihot pseudoglaziovii") com e sem fubá de milho como aditivo

O estudo foi conduzido com o objetivo de estudar o valor nutritivo da Manicoba sob a forma de silagem, com ou sem fuba de milho como aditivo. Os tratamentos utilizados foram: silagem de manicoba (SM) com quatro niveis (0; 10; 20 e 30%) de adicao de fuba de milho como aditivo, sendo cinco repeticoes por tratamento. O pH das silagens se manteve entre 4,1 e 4,3 tanto para silagens com e sem aditivo, indicando que ocorreu uma boa fermentacao lactica independente da adicao de fuba de milho. Para DIVMS ocorreram valores crescentes e significativos (P<0,05) a medida que houve aumento da adicao de fuba de milho, sendo que a inclusao de 20 % de fuba foi responsavel pelo maior valor deste parâmetro (65,1 %). As concentracoes de acido acetico e butirico foram reduzidas na medida em que foram adicionados niveis crescentes de aditivo. As concentracoes de acido lactico foram consideradas satisfatorias em todos os tratamentos. Ocorreu decrescimo significativo (p< 0,05) nos teores de FDN e FDA com a inclusao do fuba de milho, sendo encontrado o menor valor para o tratamento com 20 % de aditivo. Conclui-se que a silagem de manicoba e uma alternativa alimentar de bom valor nutricional, principalmente quando adicionado de fuba de milho como aditivo. O melhor nivel de inclusao de fuba de milho na silagem da manicoba e de 20%.