Accelerated secretion of brain natriuretic peptide from the hypertrophied ventricles in experimental malignant hypertension.

Abstract

Plasma concentrations of immunoreactive (ir) atrial (ANP) and brain (BNP) natriuretic peptldes were measured in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in the malignant phase of hypertension caused by deoxycorticosterone acetate (DOCA)-salt in SHR. The secretory rate of ANP and BNP were examined in the perfusion of isolated beating heart before and after atrial removal. Plasma irANP and irBNP in mature SHR were higher than those of control Wistar-Kyoto (WKY) rats, whereas ANP and BNP values in young SHR did not differ from those of control WKY rats. DOCA-salt treatment for 8 weeks markedly increased blood pressure, ventricular weight, and plasma irANP and irBNP in SHR. ANP and BNP values were positively correlated with ventricular weight in DOCA-salt SHR. The secretory rate of ANP and BNP from the perfused whole heart were much higher in DOCA-salt SHR than other rat groups. A large amount of BNP was secreted from the hypertrophied ventricles in DOCA-salt SHR. In contrast, ANP was mainly secreted from the atrium in all rat groups. High-performance liquid chromatography profiles of extract in plasma showed that a major component of irANP and irBNP corresponded to synthetic rat ANP-(l-28) and rat BNP-45, respectively. Results suggest that both rat ANP-(l-28) and rat BNP-45 are markedly increased in plasma in DOCA-salt-induced malignant hypertension of SHR and that the major source of circulating BNP is the hypertrophied ventricles in this model. A trial natriuretic peptide (ANP) is a diuretic, /\ natriuretic, and vasodilatory peptide hor-A. ^ mone originally isolated from the mammalian heart. 1 -2 Brain natriuretic peptide (BNP) was first identified in the porcine brain 3 and later isolated from the porcine heart. 4 Porcine BNP consists of 26 amino acid residues with much homology with the sequence of ANP.3 BNP elicits a spectrum of diuretic, natriuretic, and hypotensive effects similar to that of ANP.3 Later, a low molecular weight form of rat BNP, rat BNP-45, which was identical to the amino acid sequence (51-95) of the rat BNP precursor deduced from the complementary DNA sequence, was found in the rat atrium. Here, to assess any changes in plasma concentrations of ANP and BNP in experimental hypertension, we measured plasma concentrations of immunoreactive (ir) ANP and irBNP in young and mature sponFrom the First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.Address for correspondence: Masakazu Kohno, MD, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.Received September 3, 1991; accepted in revised form October 23, 1991. taneously hypertensive rats (SHR) and in agematched Wistar-Kyoto (WKY) rats. In addition, we measured plasma concentrations of irANP and irBNP in the experimental model of malignant hypertension caused by deoxycorticosterone acetate (DOCA) plus salt in SHR. Furthermore, the secretory rate of irANP and irBNP were examined in the perf...

Molecular cloning of hamster brain and atrial natriuretic peptide cDNAs. Cardiomyopathic hamsters are useful models for brain and atrial natriuretic peptides.

“…7). This observation indicates the accelerated secretion of ANP from atrial storage pool, which is consistent with the previous reports on DOCA-salt rats and cardiomyopathic hamsters (15,25). By contrast, both of the BNP-LI and BNP mRNA concentrations in the atrium were 1.5-fold increased in both cardiomyopathic strains (Fig.…”

“…In the BIO14.6 strain, spotty cellular myolysis in the heart occurs at 6 wk of age. Ventricular hypertrophy ensues in a progressive manner after [14][15][16][17] wk, and becomes most prominent at 30-40 wk of age.…”

“…BNP synthesis and secretion are augmented in diseased ventricles (12)(13)(14)(15)(16)(17)(18)(19). We previously reported that the plasma BNP concentration (0.9 fmol/ml) is only one sixth of the plasma ANP concentration in normal humans, whereas it is elevated several hundredfold (-300 fmol/ml) and exceeds the plasma ANP concentration ( 200 fmol/ml) in patients with severe CHF (12).…”

“…The pathophysiological implication of BNP has so far been studied using spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA)-salt rats, and experimental AMI rats (13,15).2 In these experimental rat models, however, the plasma BNP concentration remains much lower than the elevated plasma ANP concentration simultaneously determined, which is quite different from our observations on human heart diseases ( 12). It is therefore difficult to assess the significance of BNP in human heart diseases using these rat models.…”

“…We previously demonstrated that BNP is present at the highest concentration in the heart rather than in the brain, and also that BNP is synthesized in and secreted from the heart and acts as a cardiac hormone (10, 11). Furthermore, we disclosed that BNP occurs mainly in the ventricle, which contrasts with ANP, a cardiac hormone from the atrium (12, 13).BNP synthesis and secretion are augmented in diseased ventricles (12)(13)(14)(15)(16)(17)(18)(19). We previously reported that the plasma BNP concentration (0.9 fmol/ml) is only one sixth of the plasma ANP concentration in normal humans, whereas it is elevated several hundredfold (-300 fmol/ml) and exceeds the plasma ANP concentration ( 200 fmol/ml) in patients with severe CHF (12).…”