Association between hyperhomocysteinemia and vascular dysfunction on molecular basis in acute and chronic models of experimental renal failure-possible role of folic acid

Hyperhomocysteinemia [HHcy] has recently been suggested as a risk factor for atherosclerosis [AS] in patients with chronic renal disease. Several mechanisms for HHcy-induced AS have been proposed but the molecular pathogenesis of this relation is still unclear. So far, there are no reports showing the changes in homocysteine levels in acute renal failure. We investigated whether HHcy is a common finding in acute and chronic renal failure, its relation to the pathogenesis of vascular dysfunction and its possible treatment by folic acid. 35 rats were divided into 5 groups [Gp]: Gp1 [sham operated]; Gp2 [acute ischemic renal failure]; Gp3 [treated acute ischemic renal failure]; Gp4 [chronic renal failure]; Gp5 [treated chronic renal failure]. Blood samples were collected for determination of urea, creatinine and homocysteine. Aortae were harvested for assessment of vascular endothelial growth factor [VEGF] expression and aortic content of tumor necrosis factor alpha [TNF]. Both acute [Gp2] and chronic [Gp4] models of renal failure showed higher homocysteine concentrations; increased VEGF expression and increased TNF alpha than Gpl. Folic acid treatment caused significantly lower homocysteine levels and VEGF expression in Gp3 and Gp5 than Gp2 and Gp4, while its reducing effect on TNF was only evident in acute treated model compared to Gp2. Homocysteine significantly correlates with creatinine and VEGF expression in acute models [Gp2 and 3], with urea, creatinine, TNF alpha in chronic model [Gp4] and with TNF alpha in Gp5. Our findings demonstrate that HHcy is evident in acute and chronic renal failure. Increased VEGF expression in acute failure and enhanced vascular inflammation in chronic failure could be possible mechanisms by which HHcy accelerates AS. However, the direct causal relationship between them needs further investigations. Folic acid decreases HHcy and could be useful in reducing cardiovascular risk factors in uremic patients

Effect of partial sleep deprivation on gastric functions in rats

Sleep deprivation has been associated with metabolic abnormalities, host defense failure and a variety of health problems including gastric discomforts. However, the effects of partial sleep deprivation on gastric functions have not been clearly elucidated. The present study aimed to investigate the effects of partial sleep deprivation for 2 weeks on gastric acid secretion, gastric mucosal integrity and gastric motility in rats. A specific apparatus was designed to induce sleep deprivation in our lab through random lighting of 4 lamps and ringing of a bell. Partial sleep deprivation was continued for 12 hours daily for 2 weeks. 80 male rats were used in this study, 40 as control and the other 40 were subjected to sleep deprivation. Control and partially sleep deprived rats were classified into 5 groups: in the 1[st] group, gastric contents were collected 3 hours after pyloric ligation and titrated for measurement of gastric free and total acid secretion. In the 2[nd] group, gastric mucosa was examined for detection of ulcers and calculation of mean ulcer index. In the 3[rd] group, calculation of ulcer index was done following oral administration of aspirin. In the 4[th] group, basal gastric content was determined and in the 5[th] group, gastric content after 4 hours fasting was determined and the values obtained were used to calculate percentage of food emptied through the 4 hours fasting period to the basal gastric content. Partial sleep deprivation significantly increased gastric acid secretion, induced the formation of gastric ulcers and increased ulcer index following aspirin administration. Sleep deprivation also inhibited gastric motility and emptying when compared to sleep undisturbed control group. Our results suggest that partial sleep deprivation could impair gastric functions especially gastric motility which has not been previously clarified

Angiotensin II may play a role in overload induced skeletal muscle hypertrophy in the rat model

The aim of the present work was to investigate whether the renin angiotensin system plays a role in overload induced hypertrophy in skeletal muscles. Six groups of male rats were studied, each comprising six animals: Group 1 comprised sham operated non- overloaded animals; group 2 comprised animals in which plantaris muscles of both hind limbs were mechanically overloaded by surgical sectioning of soleus and gastronemius muscles; group 3 comprised sham operated animals treated with angiotensin converting enzyme [ACE] inhibitor for two weeks; group 4 comprised mechanically overloaded animals treated with ACE inhibitor for two weeks; group 5 comprised sham operated animals treated with angiotensin receptor [AT1] blocker for two weeks and group 6 comprised mechanically overloaded animals treated with AT1 blocker for two weeks. At the end of two weeks twitch characteristics [twitch tension, time of peak tension and half relaxation time] and peak titanic force were assessed in situ. Plantaris muscle and heart wet weight normalized to tibia length and plantaris cross sectional area were measured. Serum ACE activity was also measured. It was concluded that angiotensin II possibly through an effect mediated on AT1 receptors is involved in skeletal muscle hypertrophy and fiber type transition in the fast twitch plantaris muscle subjected to mechanical overload

adrenergic system in the ischemic heart: evidence for a protective role induced by cardiac gene modulation

Twenty-one rabbits' isolated perfused hearts were used in this study. Animals were divided into three groups. Group 1 [control, non preconditioned group] received no treatment and subjected to ischemia reperfusion protocol designed for all groups. Group 2 [PE group] was preconditioned by alpha-1 adrenoceptor agonist [50 mug/kg phenylephrine [PE]] pretreatment 24 hours before induction of ischemia. Group 3 [PE and Pr group] received alpha-1 adrenergic blocker prazosin [Pr] in a dose of 50 mug/kg 15 minutes prior to administration of PE. 24 hours later, hearts were isolated and perfused in Langendorff mode. All hearts were subjected to 30 minutes of no flow ischemia, followed by 120 minutes reperfusion. The following parameters were measured at base line, during and at the end of 120 minutes reperfusion period: Left ventricular developed pressure [LVDP], heart rate [HR], rate pressure product [RPP], peak rate of maximum left ventricular pressure rise [dP/dTmax] and peak rate of pressure fall [dP/dTmin]. ECG changes were recorded. Expression of iNOS was also detected in left ventricular tissue of all studied groups at the end of reperfusion by reverse transcriptase polymerase chain reaction. Isolated hearts after phenylephrine pretreatment significantly improved post ischemic cardiac performance as indicated by higher: LVDP, HR, RPP, dP/dTmax and dP/dTmin and lower St segment elevation as compared to control group. Increased expression of iNOS mRNA was also demonstrated. Prazocin administration completely abrogated the improved functional recovery observed with PE alone. The phenylephrine induced expression of iNOS mRNA was attenuated when hearts received prazocin

Study of the exogenous effects of lysophosphatidyl choline on vascular and myocardial functions in isolated rat hearts and the influence of early ischemic preconditioning

The aim of this study was to examine whether ischemic preconditioning can prevent the vascular and cardiac dysfunction induced by exogenous lysophosphatidyl choline [LPC] perfusion in Langendorff perfused rat heart model. After equilibration, rats were randomly assigned into one of the following groups [n =8 per group]: Group 1 [control] treated with vehicle for 15 minutes then hearts were perfused with normal krebs for 20 minutes; group 2 [LPC-treated], hearts of this group were perfused with LPC for 15 minutes then washed out for 20 minutes and group 3 [preconditioned group] same as in group 2, but hearts were preconditioned with one cycle of 10 minutes ischemic episode and 10 minutes reperfusion. The myocardial hemodynamic measurements [left ventricular developed pressure [LVDP], heart rate [HR], rate pressure product [RPP], end diastolic pressure [EDP] as well as GOT release activity] were measured after equilibration and at the end of each phase involved in this study. Coronary perfusion pressure [CPP] as a measure of coronary vasotone was also assessed. LPC is an important target when measures have to be taken to decrease the vulnerability to IR damage. It seems possible that ischemic preconditioning protect or improve IR damage on the basis of anti LPC action