Renal hemodynamic and natriuretic effects of manganese and interactions with atrial natriuretic peptide.
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.
Lafferty
H M
HM
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Gunning
M
M
Brady
H R
HR
Brenner
B M
BM
Anderson
S
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000098:blood supply; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*
D015636:Magnesium Chloride; D008345:Manganese; D009320:Atrial Natriuretic Factor; D002122:Calcium Chloride