Me. Murphy et Je. Brayden, NITRIC-OXIDE HYPERPOLARIZES RABBIT MESENTERIC-ARTERIES VIA ATP-SENSITIVE POTASSIUM CHANNELS, Journal of physiology, 486(1), 1995, pp. 47-58
1. Nitric oxide (NO) relaxes vascular smooth muscle (VSM) by mechanism
s which are not fully understood. One possibility is that NO hyperpola
rizes membranes, thereby diminishing Ca2+ entry through voltage-depend
ent Ca2+ channels. In the current study, the effects of NO on membrane
potential of rabbit mesenteric arteries were recorded using intracell
ular microelectrodes. 2. NO, released by 3-morpholinosydnonimine (SIN-
1, 3 mu M), reversibly hyperpolarized arteries by -9.5 +/- 4.0 mV (mea
ns +/- S.D., n = 97) from a resting membrane potential of -53.1 +/- 5.
7 mV. The hyperpolarization was blocked by oxyhaemoglobin (20 mu M), a
nd only occurred in arteries pre-treated with N-omega-nitro-L-arginine
(100 mu M) or denuded of endothelium. 3. The effect of SIN-1 was conc
entration dependent (EC(50) approximate to 0.4 mu M), and its dose res
ponse was shifted to the left by zaprinast (100 mu M), an inhibitor of
cGMP-specific phosphodiesterases. 4. The hyperpolarization due to SIN
-1 was modified by changes in extracellular K+ concentration, but not
by changes in Ca2+, Na+ or Cl-. The hyperpolarization was blocked by g
libenclamide (IC50 approximate to 0.15 mu M), but not by apamin (3-300
nM), barium (5-150 mu M), tetraethylammonium (0.1-10 mM), or 4-aminop
yridine (5-500 mu M). The hyperpolarization due to lemakalim (0.03-3 m
u M), an activator of ATP-sensitive potassium channels (K-ATP), displa
yed the same sensitivities to these K+ channel blocking agents, wherea
s the endothelium-derived hyperpolarizing factor, triggered by the add
ition of acetylcholine (3 mu M), caused a hyperpolarization (-15.3 +/-
6.2 mV) that was blocked by apamin, but not by any other agent. 5. Th
ese results suggest that NO hyperpolarizes VSM in rabbit mesenteric ar
teries by activating K-ATP channels, with the accumulation of cGMP as
an intermediate step.