Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure

Yingjie Chen, Jay H. Traverse, Mingxiao Hou, Yunfang Li, Ruisheng Du, Robert J Bache

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition with sildenafil in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/dtmax) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 ± 1.4 to 23 ± 1.4 mmHg. Sildenafil (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure (P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/dtmax. Sildenafil caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals, sildenafil did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF.

Original languageEnglish (US)
Pages (from-to)H1513-H1520
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number5 53-5
DOIs
StatePublished - May 1 2003

Keywords

  • Blood flow
  • Guanosine 3′,5′-cyclic monophosphate
  • Myocardial O consumption
  • Phosphodiesterase

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