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 capacitance (veins) and resistance (arterioles) vessels in vitro and in vivo and compared with the venoselective nitrovasodilator nitroglycerin (GTN). Concentration-response curves were constructed to GTN, SNP, GSNO and SIN-1 (0.001-10 microM) in preconstricted human saphenous vein and to GTN, GSNO and SIN-1 (0.001-10 microM) in omental resistance vessels. In vivo the dilator responses of the dorsal hand vein and the forearm resistance bed were recorded during local infusions of GTN, SNP, GSNO and SIN-1 (1 pmol/min to 160 nmol/min). SNP and SIN-1 had similar arteriovenous profiles to that of GTN. SNP was equipotent with GTN in arterioles 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 after incubation of saphenous vein with superoxide dismutase. GSNO was equipotent with GTN in arterioles but 10-fold less potent in veins in vitro 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 venoselective in vivo. Endogenous carrier molecules, including glutathione, could alter the vascular profile of NO with physiological and therapeutic implications.
MacAllister
R J
RJ
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
Calver
A L
AL
Riezebos
J
J
Collier
J
J
Vallance
P
P
D001158:Arteries / Q000187:drug effects / Q000502:physiology; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D026422:S-Nitrosoglutathione; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin; D005978:Glutathione