Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The object of this review is to describe the role of the renin-angiotensin system in control of aldosterone secretion. The review focuses on the roles of the circulating renin-angiotensin (RAS) system, the activity of which is determined predominantly by control of renin secretion from the kidney and on the role of the intra-adrenal RAS. Angiotensin can bind to two types of G protein coupled receptors, the AT1 and AT2 receptors. Both receptors are found on cells from the zona glomerulosa, the site of aldosterone synthesis. Angiotensin II acting via the AT1 receptor stimulates the synthesis of aldosterone at early and late steps in the pathway. Its effect on aldosterone is influenced by a number of other factors such as plasma potassium levels, sodium status, other peptides such as ANP and adrenomedullin and proadrenomedullin N-terminal peptide. All components of the RAS are found in the adrenal gland. The activity of this intra-adrenal RAS is unmasked and amplified in nephrectomised animals. Aldosterone controls sodium transport across epithelial cells, but recently novel effects on the heart have been described.
 ...
PMID:Angiotensin and aldosterone. 1042 51

The gene for adrenomedullin (AM), a multifunctional peptide hormone, is expressed in mammalian renal tissue and has been shown to stimulate renin release. The exact cell source of this peptide and its gene-related partner, proadrenomedullin N-terminal 20 peptide (PAMP), in kidney is still uncertain. In the present study we have identified PAMP-immunoreactive cells in the kidney of different mammalian species, including man, by light microscopy. In addition, these cells have been further studied in mouse kidney by both light and electron microscopic techniques. At the light microscopic level, PAMP immunolabeling is preferentially located in the subendothelial cells of the enlarged glomerular afferent arterioles, that is, in the juxtaglomerular cells. However, these cells do not show immunolabeling for AM. At the electron microscopic level, the immunostaining appears inside the renin-containing secretory granules of the juxtaglomerular cells. These results confirm the direct link between renin and the AM peptide family and provide a morphological basis for studying the potential modulatory function of AM and PAMP in the control of renin activity. In contrast, neither AM nor PAMP immunoreactivities were detected in the kidney of nonmammalian vertebrates, other than in blood vessels of particular species, providing a new phylogenetic difference in the juxtaglomerular apparatus between mammalian and nonmammalian vertebrates.
 ...
PMID:Proadrenomedullin N-terminal 20 peptide (PAMP) immunoreactivity in vertebrate juxtaglomerular granular cells identified by both light and electron microscopy. 1056 49

The aim of this study was to evaluate the effect of orthostasis on the time course of plasma adrenomedullin concentration. On 5 different days, normotensive subjects were randomized to undergo for 30 minutes either 12 degrees, 30 degrees, 53 degrees, or 70 degrees passive head-up tilt or to remain supine. Venous blood was collected from each subject in the supine position before tilting, at 3 and 27 minutes during tilting, and at 2 and 50 minutes after orthostasis. Plasma adrenomedullin increased significantly with tilt of >/=30 degrees in a stimulus-dependent manner. Approximately half of the increase seen at 27 minutes occurred during the first 2 minutes of upright positioning; the maximum effect with 70 degrees tilt was +70%. Elevations in norepinephrine, epinephrine, aldosterone, plasma renin activity, vasopressin, heart rate, and mean arterial pressure were also significant. Hematocrit, blood density, plasma density, and plasma volume loss rose (P<0.05) at 53 degrees and 70 degrees tilt. Our results indicate that adrenomedullin may play an important role in stabilization of hemodynamics during passive orthostasis. In conclusion, plasma adrenomedullin rapidly increases with orthostatic challenge in a stimulus-dependent manner and also swiftly returns to baseline levels after the subject resumes the supine position.
 ...
PMID:Orthostatic stimuli rapidly change plasma adrenomedullin in humans. 1056 97

The actions of adrenomedullin (ADM), a 52-amino acid peptide, are not well defined in man. We, therefore, studied eight normal volunteers aged 1832 yr in a placebo-controlled crossover study. On the 2 study days, subjects received, in random order, ADM in "low" and "high" dose (2.9 pmol/kg x min and 5.8 pmol/kg x min for 2 h each) or vehicle (hemaccel) infusion on day 4 of a metabolic diet (Na+ 80 mmol/day, K+ 100 mmol/day). Achieved plasma ADM levels were in the pathophysiological range, and plasma cAMP values rose 5 pmol/L during the higher dose. Compared with time-matched vehicle infusion, high-dose ADM increased peak heart rate by 10 beats per minute (P < 0.05) and lowered diastolic (by 5 mm Hg, P < 0.01) blood pressure. Cardiac output increased in both phases of ADM (low dose, 7.6 L/min; high dose, 10.2 L/min; vehicle, 6 L/min; P < 0.05 for both). Despite a 2-fold rise in PRA during high-dose ADM (P < 0.01), aldosterone levels were unaltered. Norepinephrine levels increased by 50% during high-dose ADM (P < 0.001), but epinephrine levels were unchanged. Plasma PRL levels increased during high-dose ADM (P = 0.014). ADM had no significant effect on urine volume and sodium excretion. Infusion of ADM to achieve pathophysiological plasma levels produced significant hemodynamic effects, stimulated renin but inhibited the aldosterone response to endogenous angiotensin II, and activated the sympathetic system and PRL without altering urine sodium excretion in normal subjects.
 ...
PMID:Hemodynamic, hormonal, and renal effects of short-term adrenomedullin infusion in healthy volunteers. 1072 32

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.
 ...
PMID:Hemodynamic, hormone, and urinary effects of adrenomedullin infusion in essential hypertension. 1104 Feb 40

The cardiovascular effects of low-dose adrenomedullin (ADM, 1, 2 and 3 pmol kg-1 min-1 for 30 min each) were evaluated in six healthy subjects in a placebo controlled, cross-over study by determining cardiac volumes, systolic and diastolic function (echocardiography) and systemic haemodynamics before, during and after ADM or placebo. High-resolution ultrasound was used to evaluate changes in carotid artery distension. ADM caused a +85% increment in its plasma levels and significantly increased plasma cyclic adenyl monophosphate (cAMP). Compared with placebo, ADM induced significant decrements in left ventricular (LV) systolic diameter and systemic vascular resistance, and increments in LV posterior wall thickening, ejection fraction and cardiac index. Right and left atrial emptying fraction and carotid artery distention increased. LV diastolic function, heart rate, and plasma renin activity did not change, whereas packed cell volume increased. These results indicate that ADM influences cardiovascular function and systemic haemodynamics at physiological plasma levels in man mainly because of its vasodilating activity, leading to reduced afterload.
 ...
PMID:Effects of low-dose adrenomedullin on cardiac function and systemic haemodynamics in man. 1110 Mar 93

Hypertension is a frequent finding in uremic patients. The pathogenesis of this complication in uremia is complex and not fully elucidated. An imbalance between the vasoconstrictor and vasodilator systems may be involved in its pathogenesis. In this study we have evaluated the state of nitric oxide (NO) and adrenomedullin (ADM) in hemodialyzed patients, especially those with hypertension. We included a group of hypertensive hemodialyzed patients (n = 9) and a group of normotensive control patients (n = 10). We measured plasma renin activity, as well as plasma catecholamines, ADM, and nitrite/nitrate levels in basal conditions before starting the hemodialysis session. Plasma volume, as well as left ventricular ejection fraction were also measured. Hemodialysis patients showed plasma levels of nitrite/nitrates and ADM higher than the reference values in the normal population. We observed no differences in the plasma levels of nitrite/nitrates, but ADM levels were higher in hypertensive (278.2 +/- 15.5 pg/ml) patients than in normotensive patients (225 +/- 9.9 pg/ml) (p < 0.05). When considering all patients together, mean arterial pressure positively correlated with plasma ADM (r = 0.468, p < 0.05). Plasma volume and left ventricular ejection fraction were similar in the two groups of patients. In summary, plasma levels of nitrite/nitrates and ADM are increased in hemodialyzed patients, although only ADM levels were further increased in hypertensive patients. Our results do not suggest that a decreased production in the vasodilator factors evaluated is involved in the pathogenesis of hypertension in uremic patients.
 ...
PMID:[Increased adrenomedullin levels in hypertensive patients on maintenance hemodialysis]. 1110 Jun 63

Plasma levels of adrenomedullin are increased in chronic renal failure. The significance of this finding is uncertain, because the biological effects of adrenomedullin in renal impairment are unknown. Therefore, we studied the effects of adrenomedullin infusion in subjects with chronic renal impairment. Eight males with IgA nephropathy and plasma creatinine of 0.19+/-0.03 mmol/L (mean+/-SEM) were studied in a vehicle-controlled crossover design. Each subject was studied twice; subjects were administered either adrenomedullin at a low dose and then a high dose (2.9 and 5.8 pmol/kg per minute, respectively, for 2 hours each) or a 4-hour vehicle control (Hemaccel), in random order, on day 4 of controlled metabolic diets. Adrenomedullin infusion achieved plasma adrenomedullin concentrations in the pathophysiological range after the low (31.2+/-5.1 pmol/L) and high (47.4+/-4.3 pmol/L) dose, and plasma cAMP was increased. Compared with vehicle control, high-dose adrenomedullin increased peak heart rate (+21.7+/-3.3 bpm, P<0.01) and cardiac output (+2.9+/-0.2 L/min, P<0.01) and lowered both systolic and diastolic blood pressures by >10 mm Hg (P<0.05). Plasma renin activity, angiotensin II, and norepinephrine increased by up to 50% above baseline levels (P<0.05 for all), whereas aldosterone and epinephrine were unchanged. Urinary volume and sodium excretion increased significantly (P<0.05) with low-dose adrenomedullin, whereas creatinine clearance was stable, and proteinuria tended to decrease. In subjects with chronic renal impairment due to IgA nephropathy, adrenomedullin infusion lowered blood pressure, stimulated sympathetic activity and renin release, and caused diuresis and natriuresis. Adrenomedullin may have a role in modulating blood pressure and kidney function in renal disease.
 ...
PMID:Hypotensive and natriuretic actions of adrenomedullin in subjects with chronic renal impairment. 1135 41

Pathogenic mechanisms of chronic systolic heart failure are constantly of great interest. In recent years the neurohumoral theory of heart failure has gained attraction. According to this theory, neurohumoral mechanisms play the main role in the pathogenesis of heart failure, especially in its progression. These mechanisms can be divided into 2 categories: vasoconstrictive, mitogenic and antinatriuretic on the one hand and vasodilative, antimitogenic and natriuretic on the other one. The former consists of sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, endothelin, cytokines. The latter comprises natriuretic peptides, prostaglandins and nitric oxide. Undoubtedly unfavourable roles of sympathetic system and renin-angiotensin-aldosteron have been shown in the progression of heart failure. Data are being also gathered confirming harmful effects of endothelin and cytokines and possibly of neuropeptide Y and vasopressine. Extensive data exist that demonstrate beneficial influence of natriuretic peptide on heart failure. The roles of nitric oxide as well as recently discovered adrenomedullin and medullipin are far from clear.
 ...
PMID:[Neurohumoral mechanisms in pathophysiology of chronic heart failure]. 1139 2

Experimental data indicate that adrenomedullin (AM) interacts at various levels with the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis, but data from humans are scant. We examined the effects of intermediate-dose, short-term AM infusion on angiotensin II- and adrenocorticotrophic hormone (ACTH)-mediated hormone and haemodynamic responses in healthy subjects. Seven normal volunteers (age 18-25 years) completed a placebo-controlled crossover study. Each subject was studied on day 4 of two periods of a low-salt diet (40 mmol of sodium and 80 mmol of potassium daily), receiving incremental infusions of angiotensin II in the morning and ACTH in the afternoon of each study day, on a background infusion of AM (4 pmol.min(-1).kg(-1)) or vehicle (hemaccel). Achieved plasma AM levels (23+/-6 pmol/l) and peak angiotensin II levels (160 pmol/l) were similar on the two experimental days. While the pressor action of angiotensin II was attenuated by AM (P<0.01) and noradrenaline levels rose (P<0.05), the aldosterone response was unaltered. During ACTH infusion, AM increased heart rate (P<0.01), plasma adrenaline (P<0.01) and plasma noradrenaline (P<0.05), and augmented the cortisol response (P<0.01), but was without effect on aldosterone levels and blood pressure. We conclude that the threshold for the effects of AM on aldosterone secretion in humans is set higher than for other biological responses to this hormone, namely blood pressure, heart rate, sympathetic activity and cortisol secretion, under these experimental conditions.
 ...
PMID:Differing thresholds for modulatory effects of adrenomedullin infusion on haemodynamic and hormone responses to angiotensin II and adrenocorticotrophic hormone in healthy volunteers. 1141 Jan 22


<< Previous 1 2 3 4 5 6 7 8 9 Next >>