The present study was conducted to dissect the underlying mechanisms by which catecholamines protect cells against preservation injury.To this end, we firstly defined the cellular and molecular differences between protected and nonprotected cells and secondly defined the mediators that were involved in cold-induced damage. In conclusion we have demonstrated that catecholamines protect cells against preservation injury either by scavenging of ROS or by inhibition of ROS production.

The racemic compound carvedilol possesses two complementary pharmacological effects, vasodilation and beta-blockade. The R- and S-enantiomers of carvedilol and the racemate were investigated with respect to the beta-blocking, vasodilating, and hypotensive actions. In agreement with results obtained with other beta-blockers, only the S-enantiomer of carvedilol exerts beta-blocking effects. In contrast, no substantial difference between the enantiomers could be seen with respect to alpha-blockade. The greater hypotensive activity of S-carvedilol may be attributed to beta-blockade, which inhibits counter-regulatory mechanisms provoked by vasodilation. From these results it is concluded that there is a rationale for using carvedilol as the racemate. Using the S-enantiomer would lead to relatively strong beta-blockade with only a weak vasodilating effect. The R-enantiomer alone would act only as a hypotensive agent without beta-blockade.

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From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotensin II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.

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