Natriuretic peptides increase a K+ conductance in rat mesangial cells

Mesangial cells (MC) are a main target of natriuretic peptides in the kidney and are thought to play a role in regulating glomerular filtration rate. We examined the influence of cGMP-generating (i.e. guanosine 3',5'-cyclicmonophosphate) peptides on membrane voltages (V-m) of rat MC by using the fast whole-cell patch-clamp technique. The cGMP-generating peptides were tested at maximal concentrations ranging from 140 to 300 nmol/l. Whereas human CNP (C natriuretic peptide), rat guanylin and human uroguanylin had no significant effect on V-m of these cells, human BNP (brain natriuretic peptide), rat CDD/ANP-99-126 (cardiodilatin/atrial natriuretic peptide) and rat CDD/ ANP-95-126 (urodilatin) hyperpolarized V-m significantly by 1.6 +/- 0.4 mV (BNP, n = 8), 3.7 +/- 0.3 mV (CDD/ANP-99-126, n = 25) and 2.8 +/- 0.4 mV (urodilatin, n = 9), respectively. The half-maximally effective concentration (EC(50)) for the latter two was around 400 pmol/l each. This hyperpolarization could be mimicked with 0.5 mmol/l 8-bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and was blocked by 5 mmol/l Ba2+ The K+ channel blocker 293 B (100 mu mol/l) depolarized basal V-m by 4.3 +/- 0.4 mV (n = 8), but failed to inhibit the hyperpolarization induced by CDD/ANP-99-126 (160 nmol/l) (n = 8). The K+ channel opener cromakalim (10 mu mol/l) neither influenced basal V-m nor altered the hyperpolarization induced by 160 nmol/l CDD/ANP-99-126 (n = 8). Adenosine (100 mu mol/l) hyperpolarized V-m by 13.4 +/- 1.3 mV (n = 16). At 100 mu mol/l, 293 B did not inhibit the adenosine-induced hyperpolarization (n = 6). At 160 nmol/l, CDD/ANP-99-126 enhanced the adenosine-induced hyperpolarization significantly by 1.5 +/- 0.6 mV (n = 10). CDD/ANP-99-126 (160 nmol/l) failed to modulate the value to which V-m depolarized in the presence of 1 nmol/l angiotensin II (n = 10), but accelerated the repolarization to basal V-m by 49 +/- 20% (n = 8). These results indicate that the natriuretic peptides CDD/ANP-99-126, CDD/ANP-95-126 and BNP hyperpolarize rat MC probably due to an increase of a K+ conductance. This effect modulates the voltage response induced by angiotensin II. The natriuretic-peptide-activated conductance can be blocked by Ba2+, but not by 293 B and cannot be activated by cromakalim. This increase in the K+ conductance seems to be additive to that inducable by adenosine, indicating that different K+ channels are activated by these hormones.