AJP - Renal Physiology, Vol 251, Issue 6 1036-F1042, Copyright © 1986 by American Physiological Society
A mechanism by which atrial natriuretic factor mediates its glomerular actions
R. G. Appel, J. Wang, M. S. Simonson and M. J. Dunn
Differential in vivo glomerular effects of atriopeptin I (AP I) and
atriopeptin III (AP III) were studied in parallel with in vitro
physiological and biochemical parameters. In anesthetized Sprague-Dawley
rats, AP III, but not AP I, significantly increased glomerular filtration
rate. Image analysis microscopy was used to assess the effect of AP I and
AP III on angiotensin II (ANG II)-induced contraction of cultured rat
glomerular mesangial cells. AP III, but not AP I, inhibited ANG II-induced
mesangial cell contraction in a concentration-dependent manner. Additional
inhibitory agents included exogenous DBcGMP, 8-BrcGMP, Na nitroprusside,
and DBcAMP. AP III stimulated mesangial cell cGMP with a lower threshold
and greater maximum stimulation than AP I. Neither agent stimulated cAMP
accumulation. Since mesangial cell contractility may regulate the
glomerular capillary surface area, these results suggest that AP III
partially mediates its glomerular effects through inhibition of ANG
II-induced mesangial cell contraction. Whereas cGMP is not clearly
implicated as the mediator of this effect, it appears that both cGMP and
cAMP may regulate the state of mesangial cell contractility.
