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) 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/1. Whereas human CNP (C natriuretic peptide), rat guanylin and human uroguanylin had no significant effect on V 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 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) for the latter two was around 400 pmol/l each. This hyperpolarization could be mimicked with 0.5 mmol/1 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-Br-cGMP) and was blocked by 5 mmol/1 Ba. The K channel blocker 293 B (1O)) μmol/l) depolarized basal V by 4.3 ± 0.4 mV ( n = 8), but failed to inhibit the hyperpolarization induced by CDD/ANP-99-126 (160 nmol/1) ( n = 8). The K channel opener cromakalim (10 μmol/1) neither influenced basal V nor altered the hyperpolarization induced by 160 nmol/1 CDD/ANP-99-126 ( n = 8). Adenosine (100 μmol/1) hyperpolarized V by 13.4 ± 1.3 mV (n = 16). At 100 μmol/1, 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/1) failed to modulate the value to which V depolarized in the presence of 1 nmol/l angiotensin II ( n = 10), but accelerated the repolarization to basal V, 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 Ba, 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. [ABSTRACT FROM AUTHOR]