Ca/CaM-Stimulated and cGMP-Specific Phosphodiesterases in Vascular and Non-Vascular Tissues

Ahn, Ho-Sam; Foster, M. A.; Cable, Michael B.; Pitts, Barry J.R.; Sybertz, Edmund J.

doi:10.1007/978-1-4684-6015-5_15

Cited by 77 publications

(47 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The vasodilatory effects of sildenafil were preferentially directed at the pulmonary circulation. This observation is not surprising given the abundant expression of phosphodiesterase-5 in lung tissue [11]. Although the decrease in systemic vascular resistance may have played a role, the increase in cardiac index also serves to emphasize the importance of right ventricular unloading in heart failure patients and its potential favourable impact on diastolic ventricular interaction [12].…”

Section: Discussionmentioning

confidence: 96%

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Al‐Hesayen

Floras

Parker

2006

European J of Heart Fail

View full text Add to dashboard Cite

Background: Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase-5 inhibition on sympathetic activity in this population has not been evaluated. Methods and results: 10 patients with heart failure (ejection fraction 23 T 3%) were studied. Generalized and cardiac sympathetic activity responses to an intravenous infusion of sildenafil were measured by the norepinephrine spillover method. In response to sildenafil, there was a significant reduction in mean pulmonary artery (À 26 T 5%, P < 0.01) and mean arterial pressures (À 8 T 1%, P < 0.01). These hemodynamic responses were accompanied by a 22 T 5% reduction in cardiac norepinephrine spillover ( P < 0.02) but no change in total body norepinephrine spillover. Conclusions: The acute administration of sildenafil is associated with a modest reduction in systemic arterial blood pressure and a more substantial reduction in pulmonary arterial pressure. These hemodynamic changes are observed in the absence of systemic sympathetic activation and are associated with a reduction in cardiac norepinephrine spillover in patients with chronic heart failure. These observations are relevant given the high prevalence of erectile dysfunction in this patient population.

show abstract

Section: Discussionmentioning

confidence: 96%

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Al‐Hesayen

Floras

Parker

2006

European J of Heart Fail

View full text Add to dashboard Cite

show abstract

“…The effects of intracellular cGMP are short lived, however, due to the rapid degradation of cGMP by phosphodiesterases. 53,54 Phosphodiesterases are a family of enzymes that hydrolyze the cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cGMP, and limit their intracellular signaling properties by generating inactive products (5Ј-adenosine monophosphate and 5Ј-guanosine monophosphate, respectively). Whereas inhibition of cAMPspecific phosphodiesterases (type 3) has played a major role in the treatment of asthma (eg, theophylline) and myocardial dysfunction (eg, milronone and amrinone), drugs that specifically inhibit cAMP-specific phosphodiesterases have relatively weak effects on the pulmonary circulation.…”

Section: Rationalementioning

confidence: 99%

Medical Therapy For Pulmonary Arterial Hypertension

Badesch

Abman

Ahearn

et al. 2004

Chest

545

View full text Add to dashboard Cite

“…1 Levels of cGMP in vascular smooth muscle are tightly regulated by several cyclic nucleotide phosphodiesterase enzymes (PDEs) that catalyze cGMP degradation and terminate this second messenger signal. 2 Sildenafil (Viagra, Pfizer) is a highly selective inhibitor of PDE5 that recently has been approved for treatment of erectile dysfunction. 3 Sildenafil potentiates the activity of cGMP in the corpus cavernosum, thereby augmenting vasodilator activity of neuronally mediated NO production.…”

mentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

Traverse

Chen

et al. 2000

Circulation

View full text Add to dashboard Cite

Background-Nitric oxide (NO) causes vasodilation by stimulation of guanylate cyclase in vascular smooth muscle to produce cGMP. The resultant vasodilator effect is regulated by a family of cGMP phosphodiesterases (PDEs). Sildenafil, a selective inhibitor of PDE5 used for treatment of erectile dysfunction, has been found to cause relaxation of isolated epicardial coronary artery segments. The present study examined the effects of sildenafil on coronary blood flow and hemodynamics during exercise in normal and ischemic heart. Methods and Results-In chronically instrumented normal dogs, sildenafil 2 mg/kg PO caused a slight but significant increase in left anterior descending (LAD) coronary blood flow during resting conditions, with a nonsignificant trend toward increased coronary flow during treadmill exercise. Exercise in the presence of LAD stenosis that decreased distal coronary pressure to 57Ϯ2 mm Hg reduced LAD flow during exercise from 69Ϯ8 to 41Ϯ7 mL/min (PϽ0.05), with hypoperfusion most severe in the subendocardium. At the same distal coronary pressure, sildenafil increased LAD flow in the ischemic region to 50Ϯ11 mL/min (PϽ0.05). Increase in ischemic region blood flow produced by sildenafil was uniform across the LV wall, given that no change occurred in the transmural distribution of perfusion. Conclusions-Inhibition of PDE5 with sildenafil caused vasodilation of coronary resistance vessels with an increase of blood flow into an ischemic myocardial region during exercise in the presence of coronary artery stenosis. (Circulation.

show abstract

Ca/CaM-Stimulated and cGMP-Specific Phosphodiesterases in Vascular and Non-Vascular Tissues

Cited by 77 publications

References 7 publications

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Medical Therapy For Pulmonary Arterial Hypertension

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

Contact Info

Product

Resources

About