RELATIVE POTENCY AND ARTERIOVENOUS SELECTIVITY OF NITROVASODILATORS ON HUMAN BLOOD-VESSELS - AN INSIGHT INTO THE TARGETING OF NITRIC-OXIDE DELIVERY

The arteriovenous potency of sodium nitroprusside (SNP), linsidomine ( SIN-1) and S-nitrosoglutathione (GSNO) was determined in human capacit ance (veins) and resistance (arterioles) vessels in vitro and in vivo and compared with the venoselective nitrovasodilator nitroglycerin (GT N). Concentration-response curves were constructed to GTN, SNP, GSNO a nd SIN-1 (0.001-10 mu M) in preconstricted human saphenous vein and to GTN, GSNO and SIN-1 (0.001-10 mu M) in omental resistance vessels. In vivo the dilator responses of the dorsal hand vein and the forearm re sistance bed were recorded during local infusions of GTN, SNP, GSNO an d SIN-1 (1 pmol/min to 160 nmol/min). SNP and SIN-1 had similar arteri ovenous profiles to that of GTN. SNP was equipotent with GTN in arteri oles and veins but SIN-1 was 10-fold less potent than GTN in vitro and 100-fold less potent in vivo; the potency of SIN-1 was increased afte r incubation of saphenous vein with superoxide dismutase. GSNO was equ ipotent with GTN in arterioles but 10-fold less potent in veins in vit ro and in vivo. These results demonstrate that most nitrovasodilators are venoselective irrespective of their mechanism of biotransformation to nitric oxide (NO) and suggests that NO itself might be venoselecti ve in vivo. Endogenous carrier molecules, including glutathione, could alter the vascular profile of NO with physiological and therapeutic i mplications.