Nitroprusside Increases Cyclic Guanylate Monophosphate Concentrations during Relaxation of Rabbit Aortic Strips and Both Effects Are Antagonized by Cyanide

Abstract

CN- partially reverses the vasodilator effects of sodium nitroprusside (SNP) on vascular smooth muscle. As tested on rabbit aortic strips contracted by norepinephrine (NE), the final tension is independent of the order of addition of reagents. In the same concentration, CN- alone had no effect on tension. The ED50 values for relaxation of aortic strips for a series of directly acting agonists (nitric oxide vasodilators) were: sodium azide (N3-) 2.1 .times. 10-7 M; SNP 2.7 .times. 10-7 M; hydroxylamine (H2NOH) hydrochloride 2.5 .times. 10-6 M; human nitric oxide Hb (HbNO) 3.5 .times. 10-6 M; and sodium nitrite (NO2-) 1.2 .times. 10-4 M. In addition to SNP, CN- antagonized the vasodilator effects of N3- and H2NOH, but it failed to reverse relaxation by HbNO, NO gas, NO2-, glyceryl trinitrate, adenosine or papaverine. The only change noted in cAMP concentrations in aortic strips exposed to NE, NE + NO2- or SNP, or NE + NO2- or SNP + CN- was an increase due to NE. The only statistically significant change noted in cGMP concentrations exposed to NE, NE + NO2- or NE + NO2- + CN- was also an increase due to NE. SNP resulted in further increases in cGMP after NE, and when CN- was added, a significant decrease in cGMP followed. These results are only partially consistent with a role for cGMP in relaxation of vascular smooth muscle, but CN- may become a useful tool for the study of mechanisms of action of the nitric oxide vasodilators.