Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.
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PMID:Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. 796 64

Adrenomedullin is a novel hypotensive peptide recently discovered in human pheochromocytoma. In the present study, we measured the plasma immunoreactive adrenomedullin of healthy subjects and patients with various diseases. Immunoreactive adrenomedullin was found to circulate in blood of the healthy subjects at a considerable concentration (3.3 +/- 0.3 fmol/ml). Plasma adrenomedullin was significantly increased in the patients with congestive heart failure (5.4 +/- 0.3 fmol/ml), essential hypertension (5.3 +/- 0.4 fmol/ml) and renal disease (4.9 +/- 0.4 fmol/ml). In healthy volunteers physical exercise significantly increased the plasma adrenomedullin concentration. The increase of adrenomedullin was inversely related to systolic blood pressure. These findings indicate that adrenomedullin participates in the circulation control in both physiological and diseased conditions. Although the exact origin of circulating adrenomedullin is still unknown, it is thought to be released rapidly by acute exercise, thereby regulating the cardiovascular system by its vasodilating activity.
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PMID:Plasma adrenomedullin in various diseases and exercise-induced change in adrenomedullin in healthy subjects. 856 10

We designed the present study to assess any changes in plasma concentrations of the novel vasorelaxant peptide adrenomedullin in patients with essential hypertension. Plasma adrenomedullin concentrations were measured in 45 patients with untreated essential hypertension, 15 patients with borderline hypertension, and 30 normotensive control subjects. After 4 weeks of effective calcium channel blocker-based antihypertensive therapy, adrenomedullin concentrations were measured again. The concentrations were higher in hypertensive patients with increased serum creatinine levels or decreased glomerular filtration rates compared with borderline hypertensive patients and normotensive subjects, although values in normotensive and hypertensive individuals overlapped. Plasma adrenomedullin concentrations were positively correlated with serum creatinine levels and inversely correlated with glomerular filtration rates in the hypertensive patients, whereas adrenomedullin values were not correlated with blood pressure level, left ventricular mass index, or left ventricular ejection fraction. Despite blood pressure control with antihypertensive therapy, plasma adrenomedullin concentrations were not changed. Reversed-phase high-performance liquid chromatographic analysis showed that a major component of immunoreactive adrenomedullin in the plasma of normotensive subjects and hypertensive patients is human adrenomedullin-(1-52). These results indicate that plasma adrenomedullin concentrations are elevated in many hypertensive patients with renal dysfunction and its major component is human adrenomedullin-(1-52).
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PMID:Plasma adrenomedullin concentrations in essential hypertension. 859 70

1. Responses of adrenomedullin to acute and chronic salt loading were examined in normotensive and hypertensive subjects. 2. In the acute salt load study, isotonic saline (50 ml/kg for 1 h) was intravenously infused into nine normotensive subjects and 11 patients with essential hypertension. Plasma adrenomedullin was higher in hypertensive than in normotensive subjects but was unchanged by saline infusion in either the normotensive (before infusion, 2.4 +/- 0.2 fmol/ml; after infusion, 2.4 +/- 0.1 fmol/ml) or hypertensive (before infusion, 3.0 +/- 0.1 fmol/ml; after infusion, 2.9 +/- 0.2 fmol/ml) group, while renin was suppressed and atrial natriuretic peptide was markedly increased. Plasma endothelin was not affected either. 3. In the chronic salt load study, seven normotensive subjects and 23 patients with essential hypertension underwent two 7-day periods of 30 and 260 mmol/day sodium intake. Depending on the blood pressure change, 13 hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive. Salt-sensitive hypertensive subjects had suppressed plasma renin activity even during low salt intake. Plasma adrenomedullin or endothelin were not affected by the salt intake changes in any group; however, the high salt intake increased atrial natriuretic peptide in all groups. 4. These data indicate that the circulating level of adrenomedullin is not changed by either acute or chronic salt loading in normotensive subjects and patients with essential hypertension.
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PMID:Behaviour of adrenomedullin during acute and chronic salt loading in normotensive and hypertensive subjects. 886 11

1. Adrenomedullin is a potent vasodilating peptide first isolated from phaeochromocytoma and adrenal medulla but also found in the heart, lungs and kidneys. It may also be a paracrine factor because endothelial and smooth muscle cells synthesize adrenomedullin as well as express the receptors. Adrenomedullin induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of nitric oxide. 2. We have developed a specific radioimmunoassay and measured the immunoreactivity of human adrenomedullin in the plasma of 58 male subjects: eight with essential hypertension, 12 with heart failure, 10 with ascites due to cirrhosis, 12 with chronic renal failure, four with hypoxia due to chronic obstructive pulmonary disease and 12 control subjects. 3. Plasma levels (mean +/- SEM) in patients with essential hypertension (16.3 +/- 1.9 pmol/l), congestive heart failure (17.5 +/- 2.8 pmol/l) and renal failure (17.7 +/- 2.5 pmol/l) were raised compared with control subjects (7.8 +/- 1.4 pmol/l, P < 0.05), confirming previous reports. 4. In addition, we observed that plasma levels of adrenomedullin were significantly raised in patients with ascites due to liver cirrhosis (15.5 +/- 1.9 pmol/l) and chronic obstructive pulmonary disease with hypoxia (20.0 +/- 1.5 pmol/l). 5. We concluded that the plasma level of adrenomedullin is raised in a variety of diseases.
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PMID:Elevated plasma levels of human adrenomedullin in cardiovascular, respiratory, hepatic and renal disorders. 903 92

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater increments in hypertensive patients than in normotensives. Plasma concentrations of BNP increased only in patients with hypertension and the levels of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography. In contrast, plasma adrenomedullin did not change with exercise in either group. These results suggest that secretion patterns of these peptides are regulated by different mechanisms and that the amount and kind of peptides mobilized by exercise may depend on the underlying diseases or pathophysiologic condition.
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PMID:Different secretion patterns of adrenomedullin, brain natriuretic peptide, and atrial natriuretic peptide during exercise in hypertensive and normotensive subjects. 914 Jul 11

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.
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PMID:Plasma adrenomedullin concentrations and cardiac and arterial hypertrophy in hypertension. 932 16

Vasopeptidase inhibition is a new concept in cardiovascular therapy. It involves simultaneous inhibition with a single molecule of two key enzymes involved in the regulation of cardiovascular function, neutral endopeptidase (EC 24.11; NEP) and angiotensin-converting enzyme (ACE). Simultaneous inhibition of NEP and ACE increases natriuretic and vasodilatory peptides (including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP] of myocardial cell origin, and C-type natriuretic peptide [CNP] of endothelial cell origin) and increases the half-life of other vasodilator peptides including bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide system, vasopeptidase inhibitors (VPIs) reduce vasoconstriction and enhance vasodilation, thereby decreasing vascular tone and lowering blood pressure. Omapatrilat, a heterocyclic dipeptide mimetic, is a novel vasopeptidase inhibitor and a single molecule that simultaneously inhibits NEP and ACE with similar inhibition constants. Unlike ACE inhibitors, omapatrilat demonstrates antihypertensive efficacy in low-, normal-, and high-renin animal models. Unlike NEP inhibitors, omapatrilat provides a potent and sustained antihypertensive effect in spontaneously hypertensive rats (SHR), a model of human essential hypertension. In animal models of heart failure, omapatrilat is more effective than ACE inhibition in improving cardiac performance and ventricular remodeling and prolonging survival. Omapatrilat effectively reduces blood pressure, provides target-organ protection, and reduces morbidity and mortality from cardiovascular events in animal models. Omapatrilat is the first VPI to enter advanced USA clinical trials. Omapatrilat appears to be a safe, well-tolerated and effective antihypertensive in humans. Vasopeptidase inhibition is a novel and efficacious strategy for treating cardiovascular disorders, including hypertension and heart failure, that may offer advantages over currently available therapies.
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PMID:Vasopeptidase inhibition: a new concept in blood pressure management. 1034 Aug 42

The novel hypotensive peptide, proadrenomedullin N-terminal 20 peptide (PAMP), is processed from the adrenomedullin precursor. Recently, we identified PAMP-12 [PAMP(9-20)] from the porcine adrenal medulla as a major endogenous and biologically active peptide. Using a new, sensitive radioimmunoassay which recognizes the C-terminal region of PAMP-20 [PAMP(1-20)], we investigated the role of PAMP in patients with essential hypertension who had normal renal function, and whether PAMP-12 is present in humans. The mean PAMP plasma concentration, like that of adrenomedullin, was significantly higher in hypertensive [1.51 fmol/mL, standard error of the mean (SEM) 0.09 fmol/mL] than normotensive participants (1.08 fmol/mL, SEM 0.05). The increase in plasma PAMP concentration in patients with organ damage accompanied by hypertension was significantly higher than that in patients without organ damage. The PAMP concentration had a significant positive correlation with mean blood pressure and adrenomedullin concentration. The immunoreactive PAMP in human tissue and plasma was characterized by reverse-phase high-performance liquid chromatography. PAMP-12, as well as PAMP-20, was abundant in the phaeochromocytoma tissue. These findings suggest that PAMP plays some pathophysiological role against the development of essential hypertension.
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PMID:Increased plasma proadrenomedullin N-terminal 20 peptide in patients with essential hypertension. 1050 13

We examined the effects of the vasodilator peptide adrenomedullin (AM) infused intravenously into subjects with essential hypertension. Eight men 39 to 58 years old with uncomplicated hypertension (147/96+/-5/3 mm Hg at baseline) were studied in a placebo-controlled, crossover design. Each subject received intravenous AM in a low and a high dose (2.9 and 5.8 pmol. kg(-1). min(-1) for 2 hours each) or vehicle-control (Hemaccel) infusion in a random order on day 4 of a controlled metabolic diet (80 mmol/d Na(+), 100 mmol/d K(+)). Plasma AM reached pathophysiological levels during infusion (18+/-4 pmol/L in low dose, 34+/-9 pmol/L in high dose) with a concurrent rise in plasma cAMP (+8.4+/-1.2 pmol/L, P:<0. 05 compared with control). Compared with control, high-dose AM increased peak heart rate (+17.8+/-2.3 bpm, P<0.01), lowered systolic (-24.6+/-0.9 mm Hg; P<0.01) and diastolic (-21.9+/-1.4 mm Hg; P<0.01) blood pressure, and increased cardiac output (+1.0+/-0. 1 L/min in low dose, +2.9+/-0.2 L/min in high dose; P<0.01 for both). Despite a rise in plasma renin activity during high dose (P<0.05), aldosterone levels did not alter. Plasma norepinephrine levels increased 1295+/-222 pmol/L (P<0.001) and epinephrine increased 74+/-15 pmol/L (P<0.05) with high-dose AM compared with control. AM had no significant effect on urine volume and sodium excretion. In subjects with essential hypertension, the intravenous infusion of AM to achieve pathophysiological levels produced significant falls in arterial pressure, increased heart rate and cardiac output, and stimulated the sympathetic system and renin release without concurrent increase in aldosterone. Urinary parameters were unaltered. Although AM has potent hemodynamic and neurohumoral effects in subjects with essential hypertension, the threshold for urinary actions is set higher.
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PMID:Hemodynamic, hormone, and urinary effects of adrenomedullin infusion in essential hypertension. 1104 Feb 40


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