Effects of l-arginine and l-name on contractile function of rat intestine submitted to cold ischemic preservation

To investigate the protective effect of L-arginine, a nitric oxide [NO] donor, against cold ischemic preservation of rat intestine. Jejunal segments, excised from rats, were preserved in Ringer's lactate [RL] solution [1], RL containing L-arginine [2], RL containing L-NAME [3]; all segments were kept at 10°C for 4 hours. Comparisons were made with non preserved control segments immersed in Tyrode's solution. In vitro contractile function of jejunal segments, from all groups, was studied under basal condition and in response to acetyl choline and adrenaline. The contractile function, expressed as the contractile force and motility index, was insignificantly different in cold ischemic preserved jejunal segments from that of the controls. In both cold ischemic preserved and control segments, contraction force and motility index were augmented by acetyl choline and inhibited by adrenaline. Addition of L-arginine to the preservation medium significantly increased the basal contraction force and motility index. L-arginine did not modify the responses to acetyl choline, yet it attenuated the inhibitory effect of adrenaline on both the contraction force and motility index. Addition of L-NAME to the preservation medium did not modify either the basal contraction force or the motility index from those obtained from control or cold ischemic preserved segments, L-NAME significantly decreased the cholinergic responses when compared to those of the control, L-arginine and cold ischemic preserved groups. In response to adrenaline, L-NAME produced less inhibition than that exhibited by control or cold ischemic preserved segments; however, such inhibitory effect was less than that displayed by L-arginine under the same conditions. The augmented cholinergic response to addition of L-arginine, and its blunting by L-NAME, on rat jejunum, suggest that NO plays an important role in the motor activity of small bowel. This could be a result of improved autonomic cholinergic function and through augmenting neurotransmitter release

Enhanced coronary flow following experimental androgen deprivation by orchidectomy

Androgen deprivation is an effective treatment for patients with advanced prostate cancer. The present work was conducted to study the impact of testosterone deprivation on cardiac functions and coronary flow. Experimental androgen deprivation was induced in rats by orchidectomy, compared to sham-operated controls. Two weeks after operation, rats were subjected to measurements of body weight, plasma testosterone and ECG recording. Cardiac functions were studied on isolated perfused hearts in a Langendorff preparation, under basal conditions and following exposure to 30 minutes of global ischemia followed by another 30 minutes of reperfusion. The following parameters were assessed: heart rate [HR], peak tension [PT], time to peak tension [TPT], half relaxation time [HRT], and myocardial flow rate [MFR]. Absolute weights of different cardiac chambers and their relative weights were also determined. The orchidectoimzed [ORX] rats exhibited non significant changes in ECG parameters, significant increase in absolute weights of whole heart and left ventricle, associated with significant body weight gain. Hearts isolated from ORX rats displayed a significant increase in basal preischemic MFR compared to their matching controls. Upon isehemia reperfusion [I/R], MFR of hearts isolated from ORX rats was still higher compared to controls, After 30 minutes of reperfusion, hearts of control rats displayed non significant change in HR associated with significant decrease in MFR as compared to preisehemie values; while in hearts of ORX rats, HR was significantly decreased, and accompanied with non significant changes in MFR. The augmented MFR in response to I/R, in ORX rats,, was however associated with significant increase in TPT and HRT, indicating impaired ventricular contractility and delayed relaxation, respectively when compared to controls. Upon I/R, PT was preserved in ORX group, while it was deteriorated in the controls, as compared to the preischemia values. Expenmental androgen deprivation induced marked increase in coronary flow, possibly due to lack of the predominant vasoconstrietor effect of testosterone hormone

Age-related changes in haemostatic responses to localized cold-induced stress in rats

In the present work, age-related changes in haemostatic responses to localized cold stress in rats were investigated. The role of vitamin E supplementation, on the haemostatic responses of those stressed rats, was also studied. Three different age groups were studied; young mature rats [4 months], middle-age rats [14 months] and old-age rats [24 months]. The animals were subjected either to acute localized cold stress [1 hour] or to chronic localized cold stress [3 hours daily, for 15 days]. Age-matched control rats were maintained under standard conditions of boarding. A group of old rats was injected intramuscularly by vitamin E in a dose of 150 mg/kg-body weight/day, prior to the stress induction [daily, for 15 days]. Exposure to acute localized cold stress produced a significant elevation in the mean arterial blood pressure in the three different age groups of rats, compared to their age matched controls. On the other hand, chronic exposure to localized cold stress resulted in significant elevation in the mean arterial blood pressure [MAP] and plasma malondialdehyde [MDA] level, with an increase in platelet aggregation, and a decrease in platelet count. In addition, there were shortening in prothrombin and partial thromboplastin times, as well as a reduction in antithrombin III activity and an increase in the levels of plasma fibrinogen and fibrin degradation products in all stressed rat groups, compared to their age matched unstressed controls. These platelet hyperaggregability and blood hypercoagulability states observed in stressed rats raise the risk of thrombo-embolic manifestations. Vitamin E supplementation in old rats subjected to chronic localized cold stress produced a significant decrease in MAP and plasma MDA level, as well as inhibited the activated coagulation system induced by cold exposure in old age, evidenced by decreased platelet aggregation in response to ADP and plasma fibrinogen level, in concurrence with prolonged PTT and stimulated AT-III activity compared to stressed old rats. Further, the value of all these parameters were corrected to near normal levels, being non significantly different from the corresponding values in the normal old rats. Therefore, the therapeutic intervention with vitamin E might improve the stress- induced derangement in the haemostatic profile

Age-related changes in haemostatic responses to oxidative stress

Altered haemostatic mechanisms are known to occur in stressful situations, yet the pathophysiology of stress related dyshaemostasis is still poorly understood. In the present work, age-related changes in haemostatic responses to oxidative stress in rats with different ages were investigated. Also, the effects of vitamin E supplementation, prior to stress induction, on the haemostatic responses of those stressed rats were evaluated. Three different age groups were studied, young mature rats [4 months], middle age [14 months] and old rats [24 months]. The animals were subjected to oxidative stress by adding H[2]O[2] solution to their drinking water, in a final concentration of 3%, daily, for 21 days. The age-matched control rats drink normal tap water. A group of old rats was injected intramuscularly by vitamin E in a dose of 150 mg/kg body weight, prior to the stress induction, daily, for 21 days.Results obtained in this study demonstrated an elevation in mean arterial blood pressure, plasma malondialdehyde, and plasma fibrinogen concentrations, and fibrin degradation products, in addition to shortened prothrombin and partial thromboplastin times and inhibited antithrombin III activity, in the young and old rats subjected to H[2]O[2]-induced oxidative stress, being statistically significant compared to their age matched controls. Moreover, there were an increase in platelet aggregation and a decrease in platelet count in the stressed young and old groups, but they were statistically significant only in old rats, compared to their age matched controls. However, stressed middle-age rats showed non-significant changes in the studied parameters, except for the mean arterial blood pressure that was significantly elevated, compared to their age matched controls. From these results, it is clear that the changes in the haemostatic responses to stress were more manifest in the young and old rats, with more marked responses in the older ones. On the other hand, vitamin E supplementation in old rats, prior to the stress induction, produced a decrease in mean arterial blood pressure, platelet aggregation, plasma fibrinogen concentration and fibrin degradation products, as well as increase in platelet count and antithrombin III activity. All these changes were statistically significant compared to the vitamin E-unsupplemented stressed old rats, but they were non significantly changed from the normal controls. It is concluded that vitamin E injection, prior to stress induction, produces marvelous effects on the stress-induced derangement of the haemostatic system