Regional haemodynamic effects of cyclosporine a (CsA) in conscious rats T. Bennett, S.M. Gardiner, P.A. Kemp, J.E. March & *B Fallgren. School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH and *R&D Consultancy Skepparevägen-15, SE-246-57, Barsebäckhamn, Sweden.	Print Abstract Search PubMed for: Bennet T Gardiner SM Kemp PA March JE Fallgren B

The clinical use of CsA as an immunosuppressant is known to cause hypertension and nephropathy (Sander et al., 1996). The latter could be secondary to reduced renal perfusion since, in anaesthetised rats, CsA causes renal vasoconstriction with much less effect on the hindlimb circulation (Morgan et al., 1991). We now report the effects of CsA on renal (R), mesenteric (M) and hindquarters (H) haemodynamics measured simultaneously in conscious rats. Under anaesthesia (fentanyl and medetomidine, 300 µg kg^-1 of each i.p. reversed with nalbuphine and atipamezole, 1 mg kg^-1 of each s.c.), male, Sprague-Dawley rats (400-450g) had pulsed Doppler flow probes and, at least 14 days later, intravascular catheters, implanted. On the day after catheterisation, measurements of mean arterial blood pressure (MAP), heart rate (HR) and R, M and H Doppler shift (DS) were made, and vascular conductances (VC) calculated (DS/MAP). Animals (n=9) were randomised to receive CsA (5.9 mg kg^-1 i.v. in 260µl) or vehicle (cremophor 50µl + 210µl sterile saline) as a bolus (over 10s) on 2 consecutive days. Prior to bolus injection of CsA, resting cardiovascular variables were (mean ± s.e.mean):- HR 352±10 beats min^-1; MAP 104±2 mmHg; RDS 10.3±1.1 kHz; MDS 12.5±0.6 kHz; HDS 3.6±0.3 kHz; RVC 100±10 (kHz mmHg^-1) 10³; MVC 121±6 (kHz mmHg^-1) 10³; HVC 35±3 (kHz mmHg^-1) 10³.

Table 1. Changes in HR, MAP, RDS, MDS, HDS and RVC, MVC and HVC following CsA. Values are mean ± s.e.mean; *P 0.05 vs baseline (Friedman's test).

CsA caused a rapid and sustained pressor effect and rise in HR accompanied by reductions in MDS and MVC. In contrast, RDS increased transiently because the reduction in RVC was slow and slight. Vehicle caused a rise in MAP (9+1 mmHg at 1 min) and reduction in MVC (-14+2%), but by 4 min there were no significant effects. Our results are consistent with the pressor effects of CsA being due to the fall in MVC, and the reduction in RVC being an ineffective autoregulatory response to the rise in MAP.

This work was supported by Camurus AB, Lund, Sweden.

Morgan, B.J. et al. (1991). Hypertension, 18, 458-466.
Sander, M. et al. (1996). Am. J. Hypertens., 9, 1215-138.