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 micrograms/kg per minute) was affected by the simultaneous administration of N-acetylcysteine (10 micrograms/kg per minute) or thiosalicylic acid (10 micrograms/kg per minute), and (2) whether NG-nitro-L-arginine-methyl ester (100 micrograms/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 filtration 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.2
Lahera
V
V
Department of Physiology and Biophysics, Mayo Medical School, Rochester, Minn. 55905.
Khraibi
A A
AA
Romero
J C
JC
D000109:Acetylcholine / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013849:Thimerosal
D000959:Antihypertensive Agents; D001565:Benzoates; D013438:Sulfhydryl Compounds; C026196:2-thiosalicylic acid; D013849:Thimerosal; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine