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Cardiovascular Pharmacology Concepts

Richard E. Klabunde, PhD

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Click here for information on Normal and Abnormal Blood Pressure, a textbook published by Richard E. Klabunde (2013)

 



Natriuretic Peptides

Natriuretic peptides are peptide hormones that are synthesized by the heart, brain and other organs. Atrial natriuretic peptide (ANP) is a 28 amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (beta-adrenoceptor mediated). Therefore, elevated levels of ANP are found during hypervolemic states (elevated blood volume) and congestive heart failure. Brain-type natriuretic peptide (BNP; 32 amino acids), although first identified in the brain, is primarily produced by ventricular tissue in the heart, and like ANP, there is enhanced synthesis and release of BNP during heart failure. Neutral endopeptidase (NEP) is a circulating enzyme that degrades natriuretic peptides. Therefore, inhibition of this enzyme increases circulating levels of natriuretic peptide and potentiates their effects.
 

Cardiovascular and Renal
Actions of Natriuretic Peptides

 

  • Natriuresis
  • Diuresis
  • Improve glomerular filtration rate
    & filtration fraction
  • Inhibit renin release
    - ↓ circulating angiotensin II
    - ↓ circulating aldosterone
  • Systemic vasodilation
  • Arterial hypotension
  • Reduced venous pressure
  • Reduced pulmonary capillary
    wedge pressure

Cardiovascular and renal effects

Natriuretic peptides are involved in the long-term regulation of sodium and water balance, blood volume and arterial pressure. These peptide hormones decrease aldosterone release by the adrenal cortex, increase glomerular filtration rate (GFR) and filtration fraction, produce natriuresis and diuresis (potassium sparing), and decrease renin release, thereby decreasing circulating levels of angiotensin II. These actions contribute to a reduction in blood volume and therefore central venous pressure (CVP), pulmonary capillary wedge pressure, cardiac output, and arterial blood pressure. Chronic elevations of ANP appear to decrease arterial blood pressure primarily by decreasing systemic vascular resistance. The mechanism of systemic vasodilation involve ANP receptor-mediated elevations in vascular smooth muscle cGMP as well as by attenuating sympathetic vascular tone.  This latter mechanism may involve ANP acting upon sites within the central nervous system as well as through inhibition of norepinephrine release by sympathetic nerve terminals. To summarize, natriuretic peptides serve as a counter-regulatory system for the renin-angiotensin-aldosterone system.

Therapeutic Uses

Heart failure

Heart failure leads to activation of the renin-angiotensin-aldosterone system, which causes increased sodium and water retention by the kidneys. This in turn increases blood volume and contributes to the elevated venous pressures associated with heart failure, which can lead to pulmonary and systemic edema. Increased angiotensin II also causes systemic vasoconstriction, which increases the afterload on the left ventricle.

The primary use for a natriuretic in heart failure is to reduce pulmonary and/or systemic congestion and edema, and associated clinical symptoms (e.g., shortness of breath - dyspnea). Natriuretics may also reduce the afterload on the heart by promoting systemic vasodilation, which can lead to improved ventricular ejection.

Specific Drugs

Recombinant human BNP, or nesiritide, is approved for use in the acute treatment of decompensated congestive heart failure caused by systolic dysfunction. As a peptide, nesiritide has poor bioavailability and therefore is only available for intravenous administration. With a short half-life of less than 20 minutes, it is administered as a continuous infusion following a bolus injection. This drug is very effective in reducing pulmonary capillary wedge pressure and improving dyspnea in this population of patients.

Adverse Side Effects and Contraindications

The most prevalent side effect of nesiritide is hypotension, which can be long-lasted. Therefore, it is important to monitor arterial pressure during drug administration. Azotemia (an elevated blood level of urea or other nitrogen containing compounds) can occur in patients with renal disease in which kidney function depends on the activated renin-angiotensin-aldosterone system. This drug should not be used in patients having cardiogenic shock or having systolic pressures less than 90 mmHg.

Revised 03/15/07

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.