AJP - Renal Physiology, Vol 258, Issue 4 998-1004, Copyright © 1990 by American Physiological Society
Renal hemodynamic and natriuretic effects of manganese and interactions with atrial natriuretic peptide
H. M. Lafferty, M. Gunning, H. R. Brady, B. M. Brenner and S. Anderson
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Manganese (Mn2+) is a cofactor for guanylate cyclase (GC), which is
involved in the generation of guanosine 3',5'-cyclic monophosphate (cGMP),
a second messenger for atrial natriuretic peptide (ANP) action. Mn2+ is
also, however, a nonselective calcium-channel blocker. We examined the
effects of infusion of MnCl2 into normal rats and its interaction in vivo
and in vitro with GC and ANP. MnCl2 significantly increased glomerular
filtration rate (GFR) and effective renal plasma flow rate (RPF). These
effects were caused by selective afferent arteriolar vasodilatation, which
allowed the glomerular capillary plasma flow rate and hydraulic pressure to
rise, thus elevating single-nephron GFR. Urinary Na+ excretion (UNaV) also
increased with MnCl2. The natriuresis was, unlike ANP, not mediated by GC
activation and cGMP production, as MnCl2 had no effect on either urinary
cGMP excretion or cGMP accumulation in intact inner medullary collecting
duct cell (IMCD) suspensions, nor did it affect Na(+)-dependent oxygen
consumption in these cells. When superimposed on an infusion of ANP, MnCl2
resulted in significant increases in UNaV, GFR, and RPF. These effects were
associated with small but significant increments in urinary cGMP excretion.
However, MnCl2 did not affect in vitro cGMP production in intact IMCDs or
glomeruli in response to ANP stimulation. It is uncertain therefore whether
the in vivo augmentation of the natriuretic effect of ANP by MnCl2 is
related to GC activation and cGMP production.
