Is atriopeptin a physiological or pathophysiological substance? Studies in the autoimmune rat.

The current studies were designed to investigate the functional significance of elevated endogenous atrial natriuretic factor (ANF) in acute congestive heart failure (CHF). Integrated cardiorenal and endocrine function were measured in three models of acute low-output congestive heart failure with comparably reduced cardiac output (CO) and mean arterial pressure (MAP). Acute CHF was produced by rapid right ventricular pacing (group I, n = 5) which decreases CO and increases atrial pressures and plasma ANF. In group II, n = 5, thoracic inferior vena caval constriction (TIVCC) was produced to decrease venous return and CO but without increases in atrial pressure or plasma ANF. In group III, n = 5, TIVCC was performed and exogenous ANF infused to achieve plasma concentrations observed in acute CHF. In acute CHF with increases in endogenous ANF, sodium excretion (UNaY), renal blood flow (RBF), plasma renin activity (PRA), and plasma aldosterone (PA) were maintained despite decreases in CO and MAP. In contrast, TIVCC with similar reductions in CO and MAP but without increases in ANF resulted in decreases in UN2V and RBF and increases in PRA and PA. Exogenous administration of ANF in TIVCC to mimic levels in acute CHF prevented sodium retention, renal vasoconstriction, and activation of renin and aldosterone. These studies demonstrate that endogenous ANF serves as an important physiologic volume regulator in acute CHF to maintain sodium excretion and possibly participate in the suppression of activation of the reninangiotensin-aldosterone system despite the stimulus of arterial hypotension.

Section: Methods Ofmeasurementsupporting

confidence: 91%

Role of endogenous atrial natriuretic factor in acute congestive heart failure.

Me¹,

Miller²,

Edwards³

et al. 1989

“…After the submission of our manuscript, Needleman's group reported the effect of autoimmunization with ANP in SHR on the development of hypertension (50). They failed to detect any alteration in the increase of blood pressure of autoimmune SHR sensitized against ANP, compared with nonimmune SHR.…”

Section: Discussionmentioning

confidence: 92%

Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Itoh¹,

Nakao²,

Mukoyama³

et al. 1989

“…Attempts to confirm a participatory role of ANF in the mineralocorticoid escape phenomenon using passive immunization with anti-ANF antiserum have produced conflicting results (22,33). However, recently, Morishita et al (34) isolated the natriuretic peptide receptor antagonist HS-142-1 (HS) from a culture broth of Aureobasidium pullulans melangimum var.…”

Section: Introductionmentioning

confidence: 99%

Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway.

Yokota

Bruneau²,

Bold³

et al. 1994

The mechanism underlying the mineralocorticoid escape phenomenon remains unknown. To assess the possible contribution of natriuretic peptides to mineralocorticoid escape, rats were injected with 5 mg deoxycorticosterone acetate for 3 d. Plasma atrial natriuretic factor (ANF) rose to twice basal levels and atrial ANF content decreased significantly by 24 h of treatment. This coincided with renal escape and with a significant increase in urinary cGMP excretion. Plasma ANF remained elevated and atrial ANF content continued to decline by 48 and 72 h while atrial ANF mRNA levels increased significantly only at 72 h. Plasma brain natriuretic peptide did not increase during escape although atrial brain natriuretic peptide mRNA levels increased significantly. Chronically administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled natriuretic peptide receptors, significantly and dose-dependently impaired the escape phenomenon. The highest dose of HS completely suppressed the increase in urinary cGMP. Despite the continued suppression, partial escape was observed by the end of the observation period. HS alone influenced neither plasma nor tissue or urine parameters. These findings show that despite activation of atrial ANF, blockade of the guanylate cyclase-coupled natriuretic peptide receptors impairs the ability of the kidney to escape the Na+ retaining effect of excess mineralocorticoid in a dose-dependent fashion. Later-acting, unknown mechanisms eventually come into play to mediate the escape phenomenon through a guanylate cyclase-independent pathway. Therefore, ANF of cardiac origin appears to be a major factor initiating mineralocorticoid escape through a guanylate cyclase-dependent pathway. (J.