A mechanism by which atrial natriuretic factor mediates its glomerular actions.

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.