Relaxation and cGMP formation in response to sildenafil and sodium nitroprusside in saphenous veins from normotensive and hypertensive patients

• Published in: American journal of hypertension 2002-09, Vol.15 (9), p.798-802
• Main Authors: Medina, Pascual, Segarra, Gloria, Martínez-León, Juan B, Vila, José M, Otero, Eduardo, Lluch, Salvador
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Aged; Biological and medical sciences; Cardiovascular system; Cyclic GMP - metabolism; Drug Therapy, Combination; Female; Human veins; Humans; hypertension; Hypertension - metabolism; Male; Medical sciences; Middle Aged; nitric oxide; Nitroprusside - pharmacology; noradrenergic; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - pharmacology; Piperazines - pharmacology; Purines; Saphenous Vein - drug effects; Saphenous Vein - metabolism; sildenafil; Sildenafil Citrate; Sulfones; Vasodilator Agents - pharmacology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(02)02977-1

This study was designed to measure cyclic guanosine 3′5′ monophosphate (cGMP) formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside in saphenous veins obtained from normotensive and hypertensive patients. Saphenous vein rings were obtained from 13 hypertensive and nine normotensive patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. The effect of sildenafil on sodium nitroprusside-induced cGMP formation was also assessed. Sildenafil (10 nmol/L to 100 μmol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused concentration-dependent relaxations that were of greater magnitude in veins from normotensive patients. Sildenafil (1 to 10 μmol/L) amplified the relaxation induced by sodium nitroprusside in both groups of veins, but this effect was more pronounced in veins from hypertensive patients. Levels of cGMP in response to sodium nitroprusside were significantly lower in veins from hypertensive subjects. However, in the presence of sildenafil, the increase in cGMP levels in response to sodium nitroprusside was significantly greater in the hypertensive as compared with the normotensive group. Although the relaxant effects of sildenafil are less pronounced in veins from hypertensive patients, the synergistic interaction sildenafil–sodium nitroprusside is more effective in veins from hypertensive patients, mainly due to an increase in cGMP accumulation.