Sulfhydryl group donors potentiate the hypotensive effect of acetylcholine in rats

Nitric oxide mediates the vasodilator and hypotensive responses of acetylcholine infusion. It has been reported that nitric oxide could be protected from free radical destruction by forming an S-nitrosothiol compound. Furthermore, sulfhydryl donors such as N-acetylcysteine or thiosalicylic acid enhance nitric oxide production from nitroglycerin. Consequently, the hypotensive effect of intravenous acetylcholine infusion might be potentiated during the simultaneous administration of sulfhydryl donors. The objective of the present study was to test in Okamoto spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (1) whether the hypotensive effect of acetylcholine (10 μg/kg per minute) was affected by the simultaneous administration of N-acetylcysteine (10 μg/kg per minute) or thiosalicylic acid (10 μg/kg per minute), and (2) whether N^G-nitro-L-arginine-methyl ester (100 μg/kg per minute) administration was able to reverse the changes induced by acetylcholine plus N-acetylcysteine or acetylcholine plus thiosalicylic acid. The administration of acetylcholine reduced (P<.05) mean arterial pressure in WKY rats (13±2%) and SHR (14±2%) without affecting urine flow rate, urinary sodium excretion, and glomerular nitration rate. In the presence of N-acetylcysteine, the acetylcholine-induced reduction in mean arterial pressure was potentiated (P<.05) in WKY rats (24±4%) and SHR (20±2%). These changes in mean arterial pressure were accompanied by significant reductions in urine flow rate and urinary sodium excretion in WKY rats, as well as in glomerular filtration rate in SHR. During the administration of thiosalicylic acid, the acetylcholine-induced hypotensive response was potentiated (P<.05) in both WKY rats (31±4%) and SHR (22±3%). These effects were also accompanied by significant reductions in urine flow rate, urinary sodium excretion, and glomerular filtration rate. The administration of N^G-nitro-L-arginine-methyl ester reversed (P<.05) the changes induced by acetylcholine plus N-acetyl-cysteine and acetylcholine plus thiosalicylic acid in mean arterial pressure, glomerular filtration rate, urine flow rate, and urinary sodium excretion in both rat strains. Under these conditions, urine flow rate and urinary sodium excretion levels were significantly higher than those found during the infusions of N-acetylcysteine and thiosalicylic acid, respectively. The administration of N-acetylcysteine or thiosalicylic acid, at the doses indicated, did not modify any of the measured arterial pressure or renal responses when compared with saline infusion. These results suggest that sulfhydryl donors effectively potentiated the hypotensive action of acetylcholine through a nitric oxide-dependent mechanism.