Renal and hormonal effects of phosphodiesterase III inhibition in congestive heart failure.
Evaluation of the impact of therapeutic interventions in congestive heart failure (CHF) with compounds such as the phosphodiesterase (PDE) III inhibitors must include the determination of regional blood flow and functional changes. Thus, whereas PDE III inhibitors produce a significant increase in cardiac output and reduction of systemic vascular resistance, it is necessary to understand their effects on the kidney and neurohormonal parameters. The evaluation of these effects must take into consideration both the baseline renal and neurohormonal abnormalities in CHF, and the cellular actions of PDE III inhibition, which include an increase in cyclic adenosine monophosphate and cytosolic calcium. In a group of 13 patients with CHF, milrinone therapy for 1 month did not increase renal blood flow or glomerular filtration rate, or favorably affect neurohormonal parameters. However, forearm blood flow increased proportionately with cardiac output. Therefore PDE III inhibition produces a preferential increase in skeletal muscle blood flow, which may be a relative shunting of blood from the kidney. Alternatively, PDE III inhibition may activate renal cellular mechanisms that offset the anticipated favorable response to the increase of cardiac output produced by milrinone.
Cody
R J
RJ
Division of Cardiology, Ohio State University Medical School and Hospital, Columbus.
D000450:Aldosterone / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D005542:Forearm / Q000098:blood supply; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020105:Milrinone; D009638:Norepinephrine / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000096:biosynthesis
D006728:Hormones; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D001127:Arginine Vasopressin; D000450:Aldosterone; D012083:Renin; D020105:Milrinone; D009638:Norepinephrine