AJP - Heart and Circulatory Physiology, Vol 258, Issue 3 854-H860, Copyright © 1990 by American Physiological Society
Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats
S. C. Textor, L. Smith-Powell and T. Telles
Department of Consultative Medicine/Nephrology, City of Hope National Medical Center, Duarte, California 91010.
Vasoconstriction and hypertension have been prominent during cyclosporin A
(CSA) administration. To evaluate whether CSA modulates vascular
responsiveness to pressor stimuli in the intact organism, CSA was
administered via osmotic pump (10 and 20 mg.kg-1.day-1 ip vs. olive oil
vehicle) for 2 wk. After 8 days, arterial pressure and dose-response
relationships to norepinephrine, angiotensin II, and bradykinin were
measured in conscious animals. Despite similar initial pressures,
dose-response relationships were markedly attenuated to both norepinephrine
and angiotensin II. Maximal responses were not affected, indicating a
rightward shift without loss of peak effect. Vasodilation with bradykinin
was not diminished. These changes were not evident after an acute CSA
infusion at the same dose (10 mg.kg-1.day-1 over 2 h). Treatment with
verapamil (0.505 mg/kg over 2 days) lowered basal arterial pressures but
did not change the effects of CSA on pressor sensitivity. Despite
attenuated pressor responses, renal vascular resistance was elevated and
glomerular filtration diminished during CSA administration. These
observations indicate that cyclosporin modifies vascular responsiveness to
pressor stimuli in the rat and may explain the relative resistance of this
species to cyclosporin-induced hypertension.
