Natriuretic Peptides

     Natriuretic peptides are secreted from atrial and ventricular myocardium in patients with heart failure. Among their beneficial physiologic effects, these peptides promote vasodilation and result in sodium and water excretion. The pharmacologic agent nesiritide (human recombinant B-type natriuretic peptide) replicates these effects and is available for intravenous administration to hospitalized
patients with decompensated heart failure. It results in vasodilation, augmented cardiac output, and reduction of the undesired activation of the renin–angiotensin and sympathetic nervous systems that are typical in heart failure. In some patients, it promotes diuresis.
     Nesiritide binds to G protein–coupled receptors in multiple tissues, including the blood vessels (resulting in vasodilation), kidneys, and adrenals. In the kidney, natriuresis is a consequence of several effects of the drug. An augmented GFR results from dilation of the afferent renal arterioles and constriction of the efferent renal arterioles, thereby increasing the filtered load of sodium. In the proximal tubule, AII-mediated sodium uptake is inhibited. Because the proximal tubule is where the vast majority of sodium is reabsorbed, this interruption in uptake results in sodium excretion. In the distal tubule, natriuretic peptides appear to further reduce sodium reabsorption through epithelial sodium channels. In the adrenal zona glomerulosa, the drug inhibits aldosterone synthesis, which leads to enhanced sodium excretion in the distal nephron.
     Despite these benefi ts, the clinical role of nesiritide is still being defi ned, because its use has not been shown to improve survival in heart failure patients and in one study was actually associated with increased mortality.

Phosphodiesterase-5 Inhibitor—Sildenafil
     Sildenafil, a phosphodiesterase type 5 inhibitor used to treat erectile dysfunction, has been shown to decrease pulmonary vascular resistance in patients with primary pulmonary hypertension (PPH). It inhibits the breakdown of cGMP in the pulmonary vasculature, which enhances vasodilation and oxygenation. Other phosphodiesterase inhibitors have not been shown to be effective in PPH. When combined with nitrates, sildenafi l can cause severe hypotension; therefore, these groups of drugs
should not be prescribed concurrently.