Cyclosporine A modulates baroreceptor function in kidney transplant recipients
Introduction
Kidney transplant recipients show an enhanced risk of cardiovascular diseases which might be due to deteriorations in central nervous blood pressure regulation [1]. Besides other factors, immunosuppressive drugs also probably have to be considered as a factor influencing baroreceptor function. At the present time, cyclosporine A is still the most important orally active immunosuppressant drug used in human kidney transplantation. It prolongs survival after transplantation. The therapeutical use of cyclosporine A, however, is limited due to its adverse effects. One of the most undesirable side effects is nephrotoxicity [2]. Furthermore, systemic arterial hypertension has also been reported in patients treated with cyclosporine A after kidney transplantation 3, 4. Interestingly, cyclosporine A increases the activity of the sympathetic nervous system in animals 5, 6and humans [7]. In animals, a resetting of the arterial baroreflex has been reported [6].
Recent work from the same laboratory showed a similar baroreflex sensitivity in kidney transplant recipients with low cyclosporine whole blood levels and healthy volunteers [8]. Surprisingly, the low frequency oscillation obtained after Fast Fourier Transformation (FFT) of heart rate and blood pressure was reduced. Similar results have already been reported in resting kidney transplant recipients [9]. The purpose of the present study was, therefore, to compare baroreceptor sensitivity in kidney transplant recipients with low and high cyclosporine whole blood levels to get information on a possible influence of this immunosuppressive drug on baroreceptor function and sympathetic tone.
Section snippets
Subjects and methods
Fourteen male and six female renal transplant recipients which had been given a donor kidney 19±19 months ago and therefore underwent immunosuppression by cyclosporine A (Sandimmun) were included in this study. None of the patients had a history of hypertension, heart disease or any abnormal findings on history, physical examination, or electrocardiography. Except for cyclosporine (125±15 mg during the first measurement), the patients did not receive any drugs until the end of the second
Study protocol
After a 20-min rest period, the registrations were performed from 7:45 to 8:15 a.m. (low cyclosporine whole blood levels). Cyclosporine A application took place exactly at 8:00 a.m. After another 20-min rest period, the second measurement was registered from 09:45 to 10:15 a.m. (our experiences show that then the cyclosporine concentration peak is reached) with no exception. The continuous registrations were performed simultaneously with the beat-to-beat-measurements. Physiological calibration
Data analysis
Blood pressure, heart rate, sequence analysis, regressions, spectral analysis data and cyclosporine A data were subjected to Student's t-test. Data are given as mean±S.E.M. (standard error of the mean). A p<0.05 was considered to be statistically significant.
Blood pressure
In Table 2 blood pressure and heart rate data at low and high cyclosporine whole blood levels are summarised. The increase in cyclosporine A whole blood levels from 101±13 to 469±52 ng/ml had no significant influence on mean arterial blood pressure. Heart rate, however, showed a statistically significant increase 2 h following cyclosporine A intake.
In Fig. 1 baroreceptor sensitivity data under low and high cyclosporine whole blood levels are depicted. The increase in cyclosporine concentrations
Discussion
The present study of 20 normotensive kidney transplant recipients investigated baroreceptor function under basal conditions and 2 h after cyclosporine A intake to get information on a possible participation of this immunosuppressive drug in the development of baroreceptor dysfunction in kidney transplant recipients. In contrast to other investigations published previously, the sequence analysis technique [11]and FFT was used. The potential importance of these techniques is in particular related
Acknowledgements
This work was supported by a grant (01EC9801/4) of the German Federal Ministry of Science and Technology.
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