Effects of ethacrynic acid and cystamine on sodium nitroprusside-induced relaxation, cyclic GMP levels and guanylate cyclase activity in rat aorta.
1. Ethacrynic acid, an agent that alkylates sulfhydryl residues, inhibited sodium nitroprusside- and 8-bromo cyclic GMP-induced relaxations. 2. Sodium nitroprusside-induced increased levels of cyclic GMP were unaltered by ethacrynic acid. 3. Concentrations of ethacrynic acid that inhibited sodium nitroprusside-induced relaxation did not affect sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase, while a higher concentration of ethacrynic acid did inhibit the activation. 4. Cystamine, an agent that oxidizes sulfhydryl residues, inhibited sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase. Exposure of intact rat aorta to cystamine inhibited basal guanylate cyclase activity in the particulate fraction but, in general, not in the soluble fraction. 5. These results are consistent with the hypothesis that vascular smooth muscle relaxation requires sulfhydryl groups. The sulfhydryl groups that presumably are alkylated by ethacrynic acid are not contained within guanylate cyclase and are involved at a regulatory step after the formation of cyclic GMP. The sulfhydryl groups altered by cystamine may be located on particulate guanylate cyclase and a role for particulate guanylate cyclase in nitrovasodilator-induced relaxation needs to be examined further.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003538:Cystamine / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005292:Ferricyanides / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005292:Ferricyanides; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011189:Potassium Chloride; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D004976:Ethacrynic Acid; D003538:Cystamine