Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels.
BACKGROUND
Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison.


METHODS
Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied.


RESULTS
Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC50 values.


CONCLUSIONS
The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.
Medina
P
P
Department of Physiology, University of Valencia, Spain.
Segarra
G
G
Martínez-León
J B
JB
Vila
J M
JM
Aldasoro
M
M
Otero
E
E
Lluch
S
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011688:Purinones / Q000494:pharmacology*; D017534:Radial Artery / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011688:Purinones; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast