Endothelium-dependent and -independent cGMP production is greater in arterial than venous graft tissue

SACC Qol. 17. No. 2 February 1991:59A

rbert of I30

desensitization, or

contracted with note were then rapidly recontracted with a variety of agents and reexwsed to NTG. Re-exrwsure to NTG resulted in development of tolkance with a 130-fold rightward shift in the NTG dose-response curve (E&I 1.2 x 10-S vs 9.0 x 1O-s However, &se NTG-tolerant rings relaxed in response to at&l natriuretic peptide, indicating preservation of particulate guanylate cyclase. Treatment of recontracted rings with the SH-donor N-acetvlcvsteine (IO I.&!) did not restore smooth muscle relaxation in responk ia BJTG (EC-& 2.0 x 10.5 M, n = 8), suggesting that SH denletion may not be the basis of NTG tolerance in these exbriments. ITo examine the role of soluble guanylate cyclase, narallel sets of vascular rims were recontracted with endothelin-1 in=!S)orthe onomethyl arginine (Li n = 8) after NTG ta restore sensi th endothelin-1 and L-N cle relaxation in resuonse to NTG was 8.2 x 10-g M, completelyY preserved rtSDWtiVdV.

D = I1S COHID

at deve vessels to desensitization of soluble guanylate cyclase.

exposure).

In

tolerance is related