Plasma Adrenomedullin Concentrations and Cardiac and Arterial Hypertrophy in Hypertension

Abstract

It has been reported that plasma concentrations of adrenomedullin (AM), a novel vasodilator peptide, are higher in patients with essential hypertension than those in normotensive subjects. To clarify the clinical significance of increased levels of AM in patients with essential hypertension, in this study we examined the relationship between plasma concentrations of AM and the structure of the left ventricle or carotid artery. Plasma AM concentrations; renin activity; and norepinephrine, epinephrine, and creatinine concentrations in 50 patients with untreated essential hypertension without renal dysfunction and heart failure were measured. We also measured the mean wall thickness of the left ventricle and left ventricular mass index by M-mode echocardiography and intimal-medial thickness and arterial distensibility of the carotid artery by ultrasonography. Hypertensive patients were divided into two groups: hypertensives with and those without left ventricular hypertrophy. Plasma AM concentrations in hypertensive patients with left ventricular hypertrophy were significantly higher than in hypertensive patients without left ventricular hypertrophy (7.87+/-2.70 vs 5.74+/-1.65 fmol/mL, P<.01). In all hypertensive patients, plasma AM concentrations were not correlated with blood pressure, plasma renin activity, plasma norepinephrine, plasma epinephrine, or plasma creatinine concentration. Plasma AM concentrations were positively correlated with left ventricular mass index or mean wall thickness (r=.37, P=.009; r=.40, P=.004, respectively) and inversely correlated with carotid artery distensibility (r=-.33, P=.02), whereas plasma AM concentrations were not correlated with intimal-medial thickness. These results suggest that the observed elevation of plasma AM in patients with essential hypertension with normal renal function may be partly related to cardiac hypertrophy and decreased carotid artery distensibility.

Plasma Adrenomedullin and Natriuretic Peptides in Patients with Essential or Malignant Hypertension.

“…The plasma AM significantly correlated with the systolic and diastolic blood pressures, when analyzed by putting all data from the three groups together, in the present study. In contrast, Kohno et al and Sumitomo et al found no significant relation between the plasma AM level and blood pressure in patients with essential hypertension (12,13). These discrepancies may have resulted from differences in subjects studied or in methods used for statistical analysis of the data.…”

Direct Measurement of Glycine-Extended Adrenomedullin in Plasma and Tissue Using an Ultrasensitive Immune Complex Transfer Enzyme Immunoassay in Rats

“…We used three anti-AM monoclonal antibodies (23,24): one recognized the ring structure (rAdR-2; anti-rat AM [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]), one the C-terminal amide structure (AdC-1; anti-AM[46-52]NH2), and one the middle portion (AdM-2; anti-AM [25][26][27][28][29][30][31][32][33][34][35][36]) of the molecule. These antibodies were gifted from Shionogi & Co., Ltd., Osaka, Japan.…”

“…Monoclonal mouse anti-AM [12][13][14][15][16][17][18][19][20][21][22][23][24][25]Fab was conjugated with 6-maleimidohexanoyl-2,4 DNP-biotinyl-BSA and used as a capture antibody (26,27 (26,27).…”

“…To measure rat AM-m, an aliquot (10 µl) of standard AM-m, plasma sample or tissue extract was mixed with 140 µl of AM buffer containing 0.1% Triton X-100, 50 KIU/ml of aprotinin, 10 fmol of 2,4-DNP-biotinyl-BSA-anti-AM [12][13][14][15][16][17][18][19][20][21][22][23][24][25] Fab conjugate (as a capture antibody) and 3 fmol of anti-AM[46-52]NH2 Fab -β-D-galactosidase conjugate (as an antibody-enzyme) and incubated overnight at 4 ºC without shaking (first incubation; Formation). Thereafter, the mixture was incubated with one streptavidin-coated polystyrene bead for 30 min at room temperature with shaking (210 strokes/min, second incubation; Entrapment).…”

“…1 (25, 27). AM was reacted simultaneously with 2,4-DNP-biotinyl-BSA-anti-AM [12][13][14][15][16][17][18][19][20][21][22][23][24][25] Figure 2 shows a typical calibration curve for rat AM-Gly, AM-m and AM-t. The lower detection limit of AM-Gly was 1 amol/assay; the assay range for plasma was 50 fmol/l (20-µl plasma samples).…”