The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension

Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53±10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9±2.5 and 10.6±2.1 pmol/l respectively; AM-Gly, 14.0±2.1 and 9.8±1.9 pmol/l respectively; AM-m, 1.9±0.6 and 1.1±0.3 pmol/l respectively; each P < 0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1±2.7 and 14.0±2.4 pmol/l respectively; AM-m, 2.0±0.6 and 0.7±0.2 pmol/l respectively; each P < 0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1±2.3 and 13.5±2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r = 0.67; AM-Gly, r = 0.63; AM-m, r = 0.59; each P < 0.001) and total pulmonary vascular resistance (AM-T, r = 0.77; AM-Gly, r = 0.70; AM-m, r = 0.75; each P < 0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.

Download Full-text

Effect of unilateral pulmonary artery occlusion on pulmonary circulation in patients with pulmonary hypertension in mitral stenosis.

Heart ◽

10.1136/hrt.31.2.172 ◽

1969 ◽

Vol 31 (2) ◽

pp. 172-177 ◽

Cited By ~ 4

Author(s):

J Widimsky ◽

J Hurych ◽

V Stanek ◽

J Kasalicky

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Pulmonary Circulation ◽

Mitral Stenosis ◽

Artery Occlusion ◽

Unilateral Pulmonary Artery Occlusion

Download Full-text

The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension

Clinical Science ◽

10.1042/cs20000119 ◽

2001 ◽

Vol 100 (1) ◽

pp. 61 ◽

Cited By ~ 10

Author(s):

Toshio NISHIKIMI ◽

Seiki NAGATA ◽

Tatsuya SASAKI ◽

Fumiki YOSHIHARA ◽

Noritoshi NAGAYA ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Circulation ◽

Mitral Stenosis ◽

Molecular Form

Download Full-text

Response of pulmonary circulation of resting, unanesthetized dogs to acute hypoxia

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.206.4.867 ◽

1964 ◽

Vol 206 (4) ◽

pp. 867-874 ◽

Cited By ~ 14

Author(s):

Otto G. Thilenius ◽

Paul B. Hoffer ◽

Robert S. Fitzgerald ◽

John F. Perkins

Keyword(s):

Cardiac Output ◽

Pulmonary Artery ◽

Left Atrium ◽

Pulmonary Circulation ◽

Normal Values ◽

Acute Hypoxia ◽

Time Sequence ◽

Low Oxygen ◽

Marked Rise ◽

Vascular Bed

By means of chronically implanted vinyl catheters, pressures in aorta, pulmonary artery (PAP), left atrium (LAP), and intrapleural space (by capsule) were recorded simultaneously and continuously, together with cardiac output (Q) by dye-dilution technic every 2 min, in unanesthetized, unsedated trained dogs for 1 hr during breathing of air and low oxygen mixtures (6–15%) via a chronic tracheostomy. In nearly all of 54 experiments on 5 animals there were striking responses to hypoxia, consisting of a marked rise in PAP (up to 120%), in Q (up to 75%), in pulmonary vascular resistance (PVR) (up to 200%), and of a significant fall in LAP. In some animals these changes were not maintained throughout hypoxia. The PVR usually returned toward normal first, followed by the PAP, while Q remained elevated. The time sequence of these events varied in different animals. Effects of the same magnitude as in hypoxia accompanied restlessness caused by stress, but fluctuated markedly, were of shorter duration, and could largely be climinated by providing quiet surroundings and by avoiding prolonged experiments. It was concluded that active vasoconstriction occurs in the pulmonary vascular bed during acute hypoxia (breathing of 6–15% O2) in the intact, unanesthetized dog. Furthermore, normal values for PAP, Q, and PVR for the resting, waking dog are reported.

Download Full-text

Quantification of physiologically significant pulmonary hypertension

Kazan medical journal ◽

10.17816/kazmj62285 ◽

1985 ◽

Vol 66 (6) ◽

pp. 470-470

Author(s):

R. A. Zaripov

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Pulmonary Circulation ◽

Systematic Approach ◽

The State ◽

Aortic Artery

On the basis of a systematic approach to the analysis of the state of the pulmonary circulation, it is proposed to assess the degree of pulmonary hypertension not by absolute figures of pressure, but in relative values, representing the ratio of pressure in the pulmonary artery to aortic artery, correlated with the proper value.

Download Full-text

The Prevalence of Pulmonary Hypertension Among Maintenance Dialysis Patients With ESRD and Its Associated Factors: A Retrospective Study

Frontiers in Medicine ◽

10.3389/fmed.2020.570874 ◽

2020 ◽

Vol 7 ◽

Author(s):

Ying Zhang ◽

Xiao-Han Ding ◽

Rongsheng Rao ◽

Yiqin Wang ◽

Fang Pang ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Left Ventricle ◽

Pulmonary Artery ◽

Left Atrium ◽

Right Atrium ◽

Associated Factors ◽

Interventricular Septum ◽

Left Ventricular ◽

Maintenance Dialysis ◽

Esrd Patients

Aim: To determine the prevalence of pulmonary hypertension (PH) and its associated factors among end-stage renal disease (ESRD) patients who underwent maintenance dialysis.Methods: A total of 491 patients received echocardiography examinations and underwent pulmonary artery systolic pressure (PASP) assessments. A subgroup of 283 patients were subjected to plasma creatinine (Cr) and blood urea nitrogen concentration (BUN) tests, routine blood examinations and electrolyte analysis. First, we compared the differences in echocardiographic, Cr and BUN, blood routine and electrolyte parameters between PH and non-PH groups. The correlations between PASP and the parameters mentioned above were also analyzed. Furthermore, univariate and adjusted logistic regression analyses were performed to identify the independent associated factors.Results: The incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6%. Most of the echocardiographic parameters, including end-diastolic internal diameters of the left atrium, left ventricle, right atrium, and pulmonary artery, as well as interventricular septum mobility, left ventricular posterior wall mobility, fractional shortening, stroke volume and left ventricle ejection fraction (LVEF), were associated with PH. Furthermore, Mg2+ (p = 0.037) and Cl− (p = 0.043) were significantly associated with PASP. However, after adjustments were made in the regression analysis, only internal diameters of the left atrium, right atrium, and LVEF were independently associated with PH.Conclusion: PH is prevalent, with a relatively high incidence among ESRD patients who undergo maintenance dialysis. The sizes of the left and right atria as well as LVEF were independently associated with PH, but further cohort and basic mechanistic studies are needed to confirm this finding.

Download Full-text

Expression and characterization of the active molecular forms of choline/ethanolamine kinase-α and -β in mouse tissues, including carbon tetrachloride-induced liver

Biochemical Journal ◽

10.1042/bj3630777 ◽

2002 ◽

Vol 363 (3) ◽

pp. 777-784 ◽

Cited By ~ 25

Author(s):

Chieko AOYAMA ◽

Akiko OHTANI ◽

Kozo ISHIDATE

Keyword(s):

Carbon Tetrachloride ◽

Mammalian Cells ◽

Molecular Form ◽

Polyclonal Antibodies ◽

Active Form ◽

Peptide Sequence ◽

Molecular Forms ◽

Native Form ◽

Ethanolamine Kinase ◽

Mouse Tissues

Choline/ethanolamine kinase (ChoK/EtnK) exists as at least three isoforms (α1, α2 and β) in mammalian cells. The physiological significance for the existence of more than one form of the enzyme, however, remains to be determined. In the present study, we examined the expression and distribution of the isoforms in mouse tissues using isoform-specific cDNA probes and polyclonal antibodies raised against each N-terminal peptide sequence. Both Northern- and Western-blot analyses indicated that either the α (α1 plus α2) or the β isoform appeared to be the ubiquitously expressed enzyme. The mRNA abundance for the α isoform was highest in testis, whereas that for the β isoform was relatively high in heart and liver. While the native form of each isoform was reported to consist of either homodimers or homotetramers, our immunotitration studies clearly indicated that a considerable part of the active form of the enzyme consists of α/β hetero-oligomers, with relatively small parts of activity expressed by α/α and β/β homo-oligomers. This is the first experimental evidence for the presence of heteromeric ChoK/EtnK in any source. Thus our results strongly suggested that the activity of ChoK/EtnK in the cell is controlled not only by the level of each isoform but also by their combination to form the active oligomer complex. Carbon tetrachloride (CCl4) was shown to induce ChoK activity 2–4-fold in murine liver. Our analysis for the mechanism involved in this induction revealed that the responsible isoform for CCl4 was α, not β. The level of α mRNA was strongly induced in mouse liver, which resulted in a sustained increase in the amount of the α isoform. Consequently, the composition of α/α homo-oligomers came to represent up to 80% of the total active molecular form of ChoK in CCl4-induced liver, whereas it was less than 20% in normal uninduced liver.

Download Full-text

Pulmonary Hypertension in Mitral Valve Disease -- Rheumatic Mitral Stenosis Versus Organic Mitral Regurgitation: The Doppler-Echocardiographic Study Revisited

10.21203/rs.3.rs-605150/v1 ◽

2021 ◽

Author(s):

Nithima Ratanasit ◽

Khemajira Karaketklang ◽

Prayuth Rasmeehirun ◽

Roongthip Chanwanitkulchai

Keyword(s):

Pulmonary Hypertension ◽

Mitral Valve ◽

Mitral Regurgitation ◽

Pulmonary Artery ◽

Mitral Valve Disease ◽

Mitral Stenosis ◽

Severe Disease ◽

Pulmonary Regurgitation ◽

Valve Disease ◽

Volume Index

Abstract Purpose: The aims of the study were to determine the factors associated with PH among patients with mitral valve disease, and the similarities and differences in the subgroups of mitral stenosis (MS) and mitral regurgitation (MR). Methods: Patients with isolated moderate to severe organic mitral valve disease were prospectively enrolled. Pulmonary hypertension (PH) was defined echocardiographically as pulmonary artery systolic pressure > 50 mmHg. Patients with MS who had mitral valve area > 1.5 cm2 and patients with MR who had effective regurgitant orifice area < 20 mm2 were excluded. Results: There were 318 patients (mean age 54.3 ± 15.5 years, 57.6% female, 66.7% MR). PH was present in 119 (37.4%) patients (48.1% and 31.8% in MS and MR, respectively). Severe mitral valve disease was reported in 245 (77.0%) patients. Left atrial (LA) diameter and pulmonary artery pressure were significantly higher in patients with MS. Dyspnea, LA volume index, significant tricuspid and pulmonary regurgitation, severe mitral valve disease and the presence of MS were independently associated with PH. Among patients with MS, LA volume index and severe disease were independently associated with PH. Significant tricuspid and pulmonary regurgitation, LA volume index and severe disease were independently associated with PH in patients with MR. Conclusions: PH is common in patients with mitral valve disease. LA volume index and severe disease were, in common, independently associated with PH in patients with mitral valve disease and in the subgroups of MS and MR.

Download Full-text