Acute renal function in chronically sympathectomized deoxycorticosterone acetate-treated miniature swine
GD Thomas and EJ Zambraski
Department of Biology-Physiology Section, Rutgers University, New Brunswick, New Jersey 08903.
We recently validated a swine model in which chronic treatment with 6-
hydroxydopamine (6-OHDA) produced an effective
sympathectomy. These
sympathectomized swine demonstrated a significantly attenuated hypertensive
response when treated with deoxycorticosterone acetate (DOCA). Because
renal nerve activity is elevated and important in controlling renal
function and blood pressure in the DOCA swine model, we wanted to study the
effect of chronic
sympathectomy on acute renal hemodynamics and tubular
function. Kidney function was assessed in 14 DOCA-treated miniature swine,
8 of which were sympathectomized by chronic treatment with 6-OHDA, while 6
served as controls. Effective renal
sympathectomy in this model has been
previously confirmed by a significant reduction (97%) of norepinephrine in
renal cortical tissue. When anesthetized, mean arterial pressure and renal
blood flow were similar between the two groups. Glomerular filtration rate
was lower by 43%, urine flow rate by 71%, sodium excretion by 66%, and
potassium excretion by 48% in the 6-OHDA DOCA animals. All of these
parameters were significantly different from the intact DOCA controls.
These results indicate that anesthetized, chronically sympathectomized
swine exhibit decreased renal excretory function. The changes in renal
function may have been due to the development of a tubular or glomerular
supersensitivity to circulating antinatriuretic factors, since the 6-OHDA
group had a 28% greater pressor response to the alpha- agonist
phenylephrine and a significantly greater fall in mean arterial pressure in
response to alpha-blockade with prazosin when compared with the controls.
These changes in renal function may also explain why the 6-OHDA animals
demonstrated a slight increase in mean arterial pressure in response to
DOCA.
Because acute renal denervation in DOCA-treated swine produces a diuresis and natriuresis, this study affirms that there may be important functional differences in acutely versus chronically denervated kidneys for which the implications under normal physiologic conditions are unknown.
Proceedings of the Society for Experimental Biology and Medicine, Vol 197, 331-336, Copyright © 1991 by Society for Experimental Biology and Medicine
