The impact of maternal cortisol concentrations on child arterial elasticity

Epidemiological studies suggest that glucocorticoid excess in the fetus may contribute to the pathophysiology of cardiovascular diseases in adulthood. However, the impact of maternal glucocorticoid on the cardiovascular system of the offspring has not been much explored in studies involving humans, especially in childhood. The objective of this study was to assess the influence of maternal cortisol concentrations on child arterial elasticity. One hundred and thirty pregnant women followed from 1997 to 2000, and respective children 5-7 years of age followed from 2004 to 2006 were included in the study. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of nine samples of saliva. Arterial elasticity was assessed by the large artery elasticity index (LAEI; the capacitive elasticity of large arteries) by recording radial artery pulse wave, utilizing the equipment HDI/PulseWave CR-2000 Cardiovascular Profiling System (R). The nutritional status of the children was determined by the body mass index (BMI). Insulin concentration was assessed by chemiluminescence, and insulin resistance by the homeostasis model assessment. Blood glucose, total cholesterol and fractions (LDL-c and HDL-c) and triglyceride concentrations were determined by automated enzymatic methods. The association between maternal cortisol and child arterial elasticity was assessed by multivariate linear regression analysis. There was a statistically significant association between maternal cortisol and LAEI (P=0.02), controlling for birth weight, age, BMI and HDL-c of the children. This study suggests that exposure to higher glucocorticoid concentrations in the prenatal period is associated to lower arterial elasticity in childhood, an earlier cardiovascular risk marker.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Background: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. Aim: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. Material and methods: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (Hbak(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Results: Patients were normotensive (systolic arterial pressure: 131.1 +/- 10.6 mmHg) and on good metabolic control (HbA(1c): 6.6 +/- 0.6%). Microalbuminuric patients presented impaired venous (32.9 +/- 17.4 vs 59.3 +/- 26.5%; p=0.004) and arterial vasodilation (1.8 +/- 0.9 vs 5.1 +/- 2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow-mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Conclusions: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis. (J. Endocrinol. Invest. 33: 696-700, 2010) (C) 2010, Editrice Kurtis

Clopidogrel, independent of the vascular P2Y(12) receptor, improves arterial function in small mesenteric arteries from Angll-hypertensive rats

The P2Y(12) receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y(12) receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates Angll (angiotensin II)-induced vascular functional changes by blockade of P2Y(12) receptors in the vasculature. Male Sprague Dawley rats were infused with Angll (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg . kg(-1) of body weight . day(-1)) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117 +/- 7.1 versus control-clopidogrel, 125 +/- 4.2; Angll vehicle, 197 +/- 10.7 versus Angll clopidogrel, 198 +/- 5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCI) vehicle-treated, 182.2 +/- 18% versus clopidogrel, 133 +/- 14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7 +/- 2.2 versus clopidogrel, 85.3 +/- 2.8) in Angll-treated animals. Vascular expression of P2Y(12) receptor was determined by Western blot. Pharmacological characterization of vascular P2Y(12) was performed with the P2Y(12) agonist 2-MeS-ADP [2-(methylthio) adenosine 5`-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %) = 71 +/- 12%) as well as contractile vascular responses (Emax % = 83 +/- 12%), these actions are not mediated by P2Y(12) receptor activation. 2-MeS-ADP produced similar vascular responses in control and Angll rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

Impacto da hipertensão arterial no remodelamento ventricular, em pacientes com estenose aórtica

FUNDAMENTO: A hipertrofia ventricular esquerda (HVE) é comum em pacientes com hipertensão arterial sistêmica (HAS) e estenose aórtica (EAo) e, com certa frequência, encontramos associação entre estas patologias. Mas, em tal situação, não está clara a importância de cada uma na HVE. OBJETIVO: 1 - Avaliar em pacientes portadores de EAo, submetidos previamente a estudo ecocardiográfico, a magnitude da HVE, nos casos de EAo isolada e associada à HAS; 2 - Avaliar o padrão de remodelamento geométrico nas duas situações. MÉTODOS: Estudo retrospectivo, observacional e transversal, incluindo 298 pacientes consecutivos, com EAo ao ecocardiograma. HVE foi considerada para massa miocárdica > 224g em homens e > 162g em mulheres. Os pacientes foram classificados como portadores de EAo leve (gradiente máximo < 30,0 mmHg), moderada (entre 30 e 50,0 mmHg) e grave (> 50,0 mmHg), além disso, foram separados em dois subgrupos: com e sem HAS. RESULTADOS: Nos três níveis de lesão aórtica, a massa ventricular esquerda foi maior na EAo associada à HAS do que na EAo isolada (EAo leve: 172 ± 45 vs 223 ± 73g, p < 0,0001; EAo moderada: 189 ± 77 vs 245 ± 81g, p = 0,0313; EAo grave: 200 ± 62 vs 252 ± 88g, p = 0,0372). Presença de HAS esteve associada a maior risco de HVE (OR = 2,1,IC95%:1,2-3,6; p = 0,012). Pacientes com EAo grave e HAS apresentaram predomínio de hipertrofia concêntrica, quando comparados com aqueles normotensos (p = 0,013). CONCLUSÃO: em pacientes com EAo, a presença de HAS foi um fator adicional de aumento da massa ventricular esquerda, interferindo também na geometria ventricular.

Prevalência de hipertensão arterial em mulheres com passado de distúrbios hiperglicêmicos na gestação

OBJETIVO: Avaliar a freqüência de hipertensão arterial (HA) em mulheres, após 3 a 12 anos da gestação-alvo e na época, classificadas em um dos 4 grupos: TGN: tolerância à glicose normal; HDG: hiperglicemia diária gestacional; DMG: diabetes melito gestacional; DMG e HDG. MÉTODOS: de 3.113 gestantes, participaram 535 mulheres selecionadas por processo aleatório e proporcional ao número em cada grupo. As mulheres TGN diferiam das demais na maioria das características clínicas consideradas. Mediu-se a pressão arterial de todas as participantes. Utilizaram-se os testes de Goodman e do qui-quadrado. RESULTADOS: A freqüência de HA foi maior nas mulheres DMG e HDG que nas TGN (40,9 vs. 23,6%; P<0,05) e intermediária, semelhante entre si e às anteriores, nas HDG e nas DMG (28,3 e 31,2%, respectivamente). Ter sido do grupo DMG e HDG dobra o risco para HA. CONCLUSÃO: Mulheres com passado de DMG e HDG têm risco aumentado para HA, além daquele para o diabetes.

Maxillo-mandibular counter-clockwise rotation and mandibular advancement with TMJ Concepts (R) total joint prostheses Part III - Pain and dysfunction outcomes

47 end-stage TMJ patients with high occlusal plane angulation, treated with TMJ custom-fitted total joint prostheses and simultaneous maxillo-mandibular counter-clockwise rotation were evaluated for pain and dysfunction presurgery (T1) and at the longest follow-up (T2). Patients subjectively rated their facial pain/headache, TMJ pain, jaw function, diet and disability. Objective functional changes were determined by measuring maximum interincisal opening (MIO) and laterotrusive movements. Patients were divided according to the number of previous failed TMJ surgeries: Group 1 (0-1), Group 2 (2 or more). Significant subjective pain and dysfunction improvements (37-52%) were observed (<0.001). MIO increased 14% but lateral excursion decreased 60%. The groups presented similar absolute changes, but Group 2 showed more dysfunction at T1 and T2. For patients who did not receive fat grafts around the prostheses and had previous failure of proplast/teflon and or silastic TMJ implants, more than half required surgery for TMJ debridement and removal of foreign body giant cell reaction and heterotopic bone formation. End-stage TMJ patients can be treated in one operation with TMJ custom-made total joint prostheses and maxillo-mandibular counter-clockwise rotation, for correction of dentofacial deformity and improvement in pain and TMJ dysfunction; Group 1 patients had better results than Group 2 patients.

Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)- angiotensin II [ANG II] receptor antagonists, respectively); d(CH2)(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V-1 receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N-W-mtro-(L)-arginine methyl ester ((L)-NAME; an NO synthase inhibitor) oil water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG 11 into the lateral septal area (LSA). Mate Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 mul over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and (L)-NAME were injected at doses of 20 and 40 mug, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. L-NAME alone increased water and sodium intake and induced a pressor effect. (L)-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while (L)-NAME potentiated it. These results suggest that both ANG II AT, and AVP V, receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response. (C) 2004 Elsevier B.V. All rights reserved.

Nitric oxide of the supraoptic nucleus influences the salivary secretion, sodium renal excretion, urinary volume and arterial blood pressure induced by pilocarpine

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their supraoptic nucleus (SON). We investigated the effects of the injection into the supraoptic nucleus (SON) of FK 409, a nitric oxide donor, and N(W-)nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (NOS), on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine, which was injected into SON. The drugs were injected in 0.5 mul volume over 30-60 s. Controls was injected with a similar volume of 0.15 M NaCl. FK 409 and L-NAME were injected at doses of 20 mug/0.5 mul and 40 mug/0.5 mul. respectively. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into SON. Injection of pilocarpine (10, 20, 40, 80, 160 mug/mul) into SON produced a dose-dependent increase in salivary secretion. L-NAME was injected into SON prior to the injection of pilocarpine into SON, producing an increase in salivary secretion due to the effect of pilocarpine. FK 409 injected into SON attenuating the increase in salivary secretion induced by pilocarpine. Mean arterial pressure (MAP) increase after injections of pilocarpine into the SON. L-NAME injected into the SON prior to injection of pilocarpine into SON increased the MAP. FK 409 injected into the SON prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (0.5 mumol/0.5 mul) injected into the SON induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the SON increased the urinary sodium excretion and urinary volume induced by pilocarpine. FK 409 injected prior to pilocarpine into the SON decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the SON. In summary the present results show: a) SON is involved in pilocarpine-induced salivation; b) that mechanism involves increase in MAP, sodium excretion and urinary volume. (C) 2003 Elsevier B.V. All rights reserved.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 mug/0.5 mul), a nitric oxide (NO) donor, and N-W-nitro-L-arginine methyl ester (L-NAME) 40 mug/0.5 mul, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested. (C) 2004 Elsevier B.V. All rights reserved.

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)(5)-Tyr(Me)-[Arg(8)]vasopressin (AAVP) and [adamanteanacetyl(1),0-ET-DTyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-[Arg(8)]vasopressin (ATAVP), which are antagonists of vasopressin V-1 and V-2 receptors, and the effects of losartan, a selective angiotensin AT(1) receptor antagonist, and CGP42112A, a selective AT(2) receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg(8)]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT(1) and AT(2) ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V-1 receptors and that the inhibitory effect requires V-2 receptors. The involvement of AT(1) and AT(2) receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance. (C) 2004 Elsevier B.V. All rights reserved.

Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas

FUNDAMENTO: O polimorfismo T-786C do gene da sintetase do óxido nítrico endotelial (eNOS) e a produção de ânion superóxido podem diminuir a produção e biodisponibilidade do óxido nítrico, comprometendo o grau de vasodilatação, podendo este efeito ser revertido pelo exercício físico. OBJETIVO: Investigar a influência do treinamento aeróbico e do polimorfismo T-786C nas concentrações dos metabólitos do óxido nítrico (NOx), no fluxo sanguíneo (FS) e na pressão arterial (PA). MÉTODOS: Trinta e duas idosas pré-hipertensas (59 ± 6 anos) foram separadas em dois grupos de acordo com o polimorfismo T-786C (TT e TC+CC). Foram analisadas as concentrações de NOx (plasma) e fluxo sanguíneo por pletismografia de oclusão venosa em repouso, 1, 2 e 3 minutos pós-oclusão (FS-0, FS-1, FS-2, FS-3, respectivamente). As avaliações foram realizadas antes e após 6 meses de um programa de exercício aeróbico. RESULTADOS: Nas avaliações pré-treinamento, os níveis de NOx foram menores no grupo TC+CC em relação ao grupo TT. O grupo TT apresentou correlações entre NOx e FS-0 (r = 0,6) e pressão arterial diastólica (PAD) e FS-0 (r = -0,7), porém nenhuma correlação foi encontrada no grupo TC+CC. Nas avaliações pós-treinamento, ocorreram correlações entre NOx e FS-0 (r = 0,6) e nas mudanças do NOx e PAD (r = -0,6) no grupo TT. Também foram obtidas correlações entre PAD e FS-1 (r = -0,8), PAD e FS-2 (r = -0,6), PAD e FS-3 (r = -0,6), nas mudanças entre NOx e FS-1 (r = 0,8) e mudanças do NOx e PAD (r = -0,7) no grupo TC+CC. CONCLUSÃO: Conclui-se que 6 meses de exercício aeróbico podem contribuir para aumentar as relações existentes entre NO, PA e FS em idosas portadores do alelo C.