Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

1.8 cineole decreases gastric compliance in anesthetized rats

PURPOSE: To study the effect of 1,8 cineoleee components of the essencial oil of Croton nepetaefolius - plant of North-East of Brasil, used in the popular medicine for riots of the gastrointestinal tract - on the motor behavior of the gut of Wistar rats. METHODS: Used 16 male animals under jejun of 24h weighing 300-350g. The effect of 1.8 cineoleee (1 or 3mg/Kg) on gastric compliance had been lead in anaesthetized rats. The variations of the gastric volume (GV), had been measured by plethysmography, while AP, HR and CVP had been monitored continuously by a digital system of data acquisition. RESULTS: Observe reduction of the GV, which was significant on 30, 40, 50 and 60min after treatment (2.0±0.1; 1.9±0.1; 1.8±0.1 and 1.7±0.1mL, versus 2.1±0.2mL). The AP presented significant fall after the administration of 1.8 cineoleee, remaining thus during 60min of monitorization (87.9±7.7; 87.6±7.1; 87.9±6.4; 87.8±5.7; 86.0±5.5 and 87.7±6.0mmHg, respectively versus 94.4±6.2 mmHg), as well as the HR (366.3±13.4; 361.7±11.5; 357.3±10.4; 353.0±10.4; 348.3±11.1 and 350.4±13.7bpm, respectively versus 395.2±11.1bpm). The CVP did not suffer significant variations after treatment. CONCLUSION: Observe the 1.8 cineoleee reduces the gastric compliance in anaesthetized rats besides presenting effect hipotensor and bradicardic; probably for direct action on the gastrointestinal and vascular smooth muscel and moduling the autonomic nervous system.

OBJETIVO: Estudar o efeito do 1.8 cineol, componente do Cróton nepetaefolius (planta do Nordeste) comumente usada na medicina popular para distúrbios do trato gastrintestinal (TGI), sobre o comportamento motor do TGI de ratos Wistar anestesiados. MÉTODOS: Utilizamos 16 animais machos, pesando entre 300 a 350g. Os estudos de complacência gástrica foram conduzidos em animais sob jejum de 24h. As variações do volume gástrico (VG), foram medidas por pletismografia, enquanto a PA, FC e PVC foram monitoradas continuamente por um sistema digital de aquisição de dados. RESULTADOS: Observamos diminuição do VG, o qual foi significativo aos 30, 40, 50 e 60min após o tratamento com 1.8 cineol quando comparado ao perído basal (2,0±0,1; 1,9±0,1; 1,8±0,1 e 1,7±0,1mL, vs 2,1±0,2mL). A PA apresentou queda significativa após a administração de 1.8 cineol, mantendo-se assim durante os 60min de monitoração (87,9±7,7; 87,6±7,1; 87,9±6,4; 87,8±5,7; 86,0±5,5 e 87,7±6,0mmHg, respectivamente vs 94,4±6,2; mmHg), bem como a FC (366,3±13,4; 361,7±11,5; 357,3±10,4; 353,0±10,4; 348,3±11,1 e 350,4±13,7bpm respectivamente vs 395,2±11,1bpm). Já a PVC não sofreu variações significativas durante após o tratamento. CONCLUSÃO: O 1.8 cineol diminui a complacência gástrica em ratos anestesiados além de apresentar efeitos hipotensor e bradicárdico; provavelmente por ação direta sobre a musculatura lisa gastrintestinal e vascular e modulação do sistema nervoso autônomo.

The Effects of Low Calcium Dialysate on Arterial Compliance and Vasoactive Substances in Patients with Hemodialysis

BACKGROUND: Considering that dialysate calcium concentration is potentially a main determinant of the serum ionized calcium level and vasoconstriction is associated with the blood calcium concentration, we conducted a study to evaluate the interdialytic effects of treatment with a low calcium dialysate (LdCa, 1.25 mmol/L) on the changes in arterial compliance (AC), blood pressure (BP), biochemical parameters and vasoactive substances. METHODS: Eight hemodialysis (HD) patients (mean age: 46.8 +/- 13.7 years, 4 men and 4 women) were included in the study. AC, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), serum ionized Ca, intact-PTH, serum nitric oxide and aldosterone were compared after 10 sessions of treatment with LdCa. Right carotid artery diameter was measured 3 times using a real time B-mode ultrasound imager (Hewlett-Packard Sonos 2000 (R) ) and AC was calculated using the Hayoz method. RESULTS: 1) AC was recorded as 0.140 (0.080-0.170) mm2/kPa at the baseline (1.75 mmol/L calcium dialysate), 0.170 (0.050-0.290) mm2/kPa after LdCa treatment (p< 0.05 versus baseline), and 0.140 (0.070-0.250) mm2/kPa following the HdCa treatment (p< 0.05 versus LdCa data). 2) MAP and PP were calculated at 114.12 +/- 10.56 mmHg and 63.50 +/- 10.87 mmHg at the baseline; 98.37 +/- 15.14 mmHg and 56.50 +/- 5.95 mmHg after LdCa treatment (p< 0.05 versus baseline) ; and 115.75 +/- 9.64 mmHg and 62.00 +/- 15.71 mmHg following HdCa treatment (p< 0.05 versus LdCa data). 3) Serum ionized Ca and intact-PTH were measured at 4.66 +/- 0.40 mg/dL and 25.08 +/- 16.44 pg/mL at the baseline; 4.45 +/- 0.28 mg/dL and 90.71 +/- 27.03 pg/mL after LdCa treatment (p< 0.05 versus baseline) ; and 4.65 +/- 0.43 mg/dL and 24.08 +/- 15.44 pg/mL following HdCa treatment (p< 0.05 versus LdCa data). 4) Serum aldosterone concentration was 300.8 (65.5-836.1) pg/mL at the baseline, and 220.2 (42.8-527.9) pg/mL after LdCa treatment (p< 0.05). CONCLUSION: There were favorable changes in AC, BP, biochemical parameters after treatment with LdCa. These changes may be associated with the reduction in serum ionized calcium and decreased serum aldosterone concentration.

Urodynamic changes following intrathecal administration of morphine and fentanyl to dogs

The effect of intrathecal [IT] injection of morphine and fentanyl on the urinary bladder was studied by ascending cystogram in 18 anaesthetized dogs. Examinations were performed before and 60 and 120 minutes after IT injection of saline [group I], 0.03 mg/kg morphine [group II] and 1.5 microg/kg fentanyl [group III]. A significant increase in maximal volume and compliance and a decrease in voiding pressure were observed, indicating relaxation of the detrusor muscle after IT administration of morphine or fentanyl. IT morphine produced greater and more prolonged bladder relaxation than IT fentanyl. We conclude that IT morphine and fentanyl cause variable degrees of urinary retention. As fentanyl produced milder and shorter bladder relaxation than morphine, it may be useful in patients with urinary disturbances