atrial-natriuretic-factor and Hypertension--Malignant

Adrenomedullin (AM), a potent vasodilator and natriuretic peptide, is found in human blood. To investigate the pathophysiological role of AM in essential and malignant hypertension (EHT and MHT), we measured the plasma concentrations of AM in patients with EHT of WHO stage I or II (n = 42) and in those with MHT (n = 9) by a specific radioimmunoassay, and compared these concentrations with those in normotensive controls (n = 46). The plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) in these subjects were also measured by immunoradiometric assays, and their relations to plasma AM were examined. The plasma AM level in the EHT patients (7.15+/-0.21 pmol/l, mean+/-SEM) was significantly (p < 0.01) higher than that in the normotensive controls (6.14+/-0.25 pmol/l), and a further elevation was observed in the MHT patients (14.1+/-3.8 pmol/l). Similar elevations of plasma ANP and BNP were seen in the two patient groups. The plasma AM level significantly (p < 0.01) correlated with not only the systolic (r = 0.44) and diastolic (r = 0.46) blood pressures, but also with the plasma levels of ANP (r = 0.43) and BNP (r = 0.43). The elevated plasma concentration of AM in the MHT patients decreased significantly (p < 0.05) after antihypertensive treatment, and the plasma ANP and BNP levels similarly declined. These results suggest that AM may participate, along with ANP and BNP, in mechanisms counteracting a further elevation of blood pressure in patients with EHT and MHT.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Calcitonin Gene-Related Peptide; Creatinine; Female; Humans; Hypertension; Hypertension, Malignant; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Radioimmunoassay; Renin

ANP-receptors affinities (KD) and capacities (Bmax) were assayed in cryosections of glomeruli from 'malignant' hypertensive rats (2K-1C) and spontaneously hypertensive rats (PHR). Plasma ANP concentration was twofold higher in 2K-1C (P < 0.05) and PHR (P < 0.02) than in the respective controls, KD and Bmax for rANP99-126 and ANP103-123 did not differ. ANP mediated cGAMP release in 2K-1C rats was also unaffected. ANP-C glomerular receptors (i.e. displacement of tracer binding with ANP103-123) were not down-regulated and had unchanged peptide binding affinity in either kidney of rats with 'malignant' hypertension and in PHR. The difference between Bmax for rANP99-126 and Bmax for rANP103-123 (ANP-A receptor binding) indicates moderate up-regulation of ANP-A receptors in the clipped, and down-regulation in the contralateral kidney of 2K-1C (2K-1C, right vs. left, P < 0.05). Since [ANP]pl, and also Bmax and KD for ANP were similar in both hypertension models investigated, changes of the [ANP]pl/ANP-receptor system can not completely explain the marked natriuresis of rats with 'malignant' hypertension.

Topics: Animals; Atrial Natriuretic Factor; Down-Regulation; Guanylate Cyclase; Hypertension; Hypertension, Malignant; Hypertension, Renovascular; Kidney Glomerulus; Kinetics; Male; Natriuresis; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

The blood pressure was decreased after chronic treatment with enalapril, MK-954, and hydralazine in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension of spontaneously hypertensive rats (SHR); however, ventricular weight and plasma brain natriuretic peptide (BNP) concentration were decreased after enalapril and MK-954 but not after hydralazine. The BNP secretory rates from the ventricle in enalapril- and MK-954-treated DOCA-salt SHR were decreased to approximately 50% of those in untreated DOCA-salt SHR. The BNP secretory rate from the ventricle was positively correlated with ventricular weight in untreated and treated DOCA-salt SHR. In contrast, acute administration of captopril or MK-954 did not decrease the BNP secretory rate from the heart. Results suggest that the decrease in plasma BNP after enalapril and MK-954 is attributed to a decline in the secretion from the ventricle but not from the atrium. The reduction in ventricular mass appeared to be related to this decline.

Topics: Animals; Atrial Natriuretic Factor; Biphenyl Compounds; Blood Pressure; Blood Urea Nitrogen; Cardiomegaly; Chromatography, High Pressure Liquid; Creatinine; Desoxycorticosterone; Enalapril; Heart; Hydralazine; Hypertension, Malignant; Imidazoles; Losartan; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Sodium, Dietary; Tetrazoles

Hyponatremia and malignant hypertension are rare manifestations of Wilms' tumor. Hyponatremia associated with malignant hypertension of any cause is not explained. We present a patient with hyponatremia, malignant hypertension, Wilms' tumor, and an elevated atrial natriuretic factor (ANF). We believe the elevated ANF caused the hyponatremia.

Topics: Atrial Natriuretic Factor; Female; Humans; Hypertension, Malignant; Infant; Renin; Sodium; Syndrome; Wilms Tumor

Plasma concentrations of immunoreactive (ir) atrial (ANP) and brain (BNP) natriuretic peptides 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-(1-28) and rat BNP-45, respectively. Results suggest that both rat ANP-(1-28) 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.

Topics: Aging; Animals; Atrial Natriuretic Factor; Cerebral Ventricles; Chromatography, High Pressure Liquid; Desoxycorticosterone; Hypertension, Malignant; Hypertrophy; In Vitro Techniques; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Osmolar Concentration; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium Chloride

The examination comprised 58 patients with essential hypertension and 17 with nephrogenic arterial hypertension. An analysis of the baseline levels of natural natriuretic factor in patients with essential and nephrogenic hypertension revealed no intergroup differences (55.3 +/- 3.0 and 45.7 +/- 5.2 ng/ml, respectively). The concentration of natural natriuretic factor was significantly higher in even patients with mild arterial hypertension than in healthy persons (28.4 +/- 4.7 and 17.4 +/- 2.9 ng/ml). There was a direct correlation between the level of natural natriuretic factor and blood pressure and left ventricular myocardial hypertrophy. There were higher positive correlations between the levels of natural natriuretic factor and those of hormones of the renin-angiotensin-aldosterone system and catecholamines in patients having a diastolic pressure of greater than 115 mm Hg. A significant increase in natural natriuretic factor levels (92.1 +/- 11.8 ng/ml) was found in the presence of hypertensive crisis.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Humans; Hypertension; Hypertension, Malignant; Hypertension, Renal; Middle Aged; Renin-Angiotensin System; Severity of Illness Index

Topics: Adrenal Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Inappropriate ADH Syndrome