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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenomedullin (AM), a novel hypotensive peptide, is suggested to be involved in defense mechanisms against hypertension, however, the detail mechanisms have not been clarified. To elucidate whether AM synthesis would be altered in a salt dependent hypertension, we have investigated the AM concentration and AM messenger RNA (mRNA) level in tissues of Dahl salt-sensitive rats on either low- or high-salt intake. The AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low-salt group. Furthermore, the plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the pathophysiology of salt dependent hypertension and plays a role in cardiac hypertrophy.
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PMID:Adrenomedullin: changes in circulating and cardiac tissue concentration in Dahl salt-sensitive rats on a high-salt diet. 888 78

We have discovered a novel hypotensive peptide, designated "adrenomedullin", in human pheochromocytoma extracts. It has potent and long-lasting vasodilatory effects in several vascular systems. In addition to adrenomedullin, another hypotensive peptide, termed PAMP, is also produced from the adrenomedullin precursor. Although initially isolated from human pheochromocytoma and porcine adrenal medullary tissue, adrenomedullin mRNA is highly expressed in several peripheral organs including cardiovascular tissues. Taken together with the presence of adrenomedullin-specific receptors on VSMCs and the significant increase in plasma immunoreactive adrenomedullin levels in patients with hypertension, renal failure and congestive heart failure, adrenomedullin may participate in the pathogenesis of these diseases as a factor regulating blood pressure and circulation.
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PMID:Adrenomedullin: a new modulator of vascular tone. 895 71

Adrenomedullin is a potent vasodilator peptide that exerts major effects on cardiovascular function. Adrenomedullin is biosynthesized in a wide variety of organs and cells, although it was initially isolated from human pheochromocytoma tissue. In addition to adrenomedullin, proadrenomedullin N-terminal 20 peptide was found to be processed from adrenomedullin precursor. Both adrenomedullin and proadrenomedullin N-terminal 20 peptide show hypotensive effects in anesthetized rats, but exhibit different hypotensive mechanisms. Further, adrenomedullin possesses multiple biological effects involved in cardiovascular homeostasis. Plasma adrenomedullin concentration is increased in patients with cardiovascular diseases such as hypertension, congestive heart failure, renal failure and septic shock. The present review summarizes the recent advancement of adrenomedullin research and demonstrates that adrenomedullin is one of the important vasoactive peptides involved in the physiology and pathophysiology of circulatory control and control of body fluid.
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PMID:Adrenomedullin--physiological regulator of the cardiovascular system or biochemical curiosity? 905 59

Adrenomedullin (ADM) was originally discovered in human pheochromocytoma but is now known to be widely distributed in various organs including the kidney. ADM is a potent hypotensive peptide that increases renal blood flow and causes natriuresis and diuresis. While ADM may act in a paracrine manner, circulating levels are increased in hypertension, chronic renal failure and congestive heart failure. Current evidence suggests that ADM may play an important role in cardiorenal homeostasis.
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PMID:Adrenomedullin: a new peptide involved in cardiorenal homeostasis? 905 44

PROPERTIES OF ADRENOMEDULLIN: We have identified a novel hypotensive peptide, adrenomedullin, in human pheochromocytoma extract. It has potent and long-lasting vasodilatory effects in several vascular systems. In addition to adrenomedullin, another hypotensive peptide, proadrenomedullin-derived peptide (PAMP), was also found to be processed from the adrenomedullin precursor. PAMP inhibits neural transmission at peripheral sympathetic nerve endings, although adrenomedullin directly dilates vascular smooth muscle. POSSIBLE INVOLVEMENT IN PATHOGENESIS: Although initially isolated from human pheochromocytoma tissue, adrenomedullin messenger RNA is highly expressed in several peripheral organs, including cardiovascular tissues. Adrenomedullin and PAMP are both synthesized and secreted from vascular smooth muscle and endothelial cells, and they participate in circulation control through different mechanisms. Taken together with the presence of adrenomedullin-specific receptors on vascular smooth muscle cells and the significant increase in plasma immunoreactive adrenomedullin levels in patients with hypertension, renal failure and congestive heart failure, adrenomedullin may be involved in the pathogenesis of these diseases.
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PMID:Adrenomedullin: a new hypotensive peptide. 912 Jun 66

Adrenomedullin (ADM), originally discovered in human pheochromocytoma, is also of renal cell origin and has natriuretic and diuretic actions. The present study was designed to investigate the role of prostaglandins and renal nerves in the renal hemodynamic and natriuretic actions ofADM. ADM was administered intrarenally (1, 5 and 25 ng x kg(-1) x min(-1)) with and without prostaglandin inhibition (meclofenamate, 5 mg/kg intravenous bolus) in anesthetized normal mongrel dogs (n = 5, each). To elucidate the role of renal nerves, ADM was administered intrarenally to the denervated kidney in five dogs. ADM mediated a natriuretic action via increases in glomerular filtration rate and decreases in distal tubular sodium reabsorption, which was attenuated by renal denervation and completely abolished by prostaglandin inhibition. The renal vasodilatation induced by ADM was attenuated by meclofenamate, as well as by renal denervation, although not significantly. Additionally, renal nerves mediated hemodynamic effects of hypertension that were produced by intrarenal infusion of ADM. This study establishes an important mechanistic role for renal prostaglandins as a mediator of ADM-mediated natriuresis at the level of the glomerulus and terminal nephron.
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PMID:Role of prostaglandins and renal nerves in the renal actions of adrenomedullin. 912 5

Shear stress is known to dilate blood vessels and exert antiproliferative effects on vascular walls: these effects have been ascribed to shear stress-induced upregulation of endothelium-derived vasoactive substances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-type natriuretic peptide (CNP) as a novel endothelium-derived relaxing peptide (EDRP) that shares a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that elevates intracellular cAMP as prostacyclin does. To elucidate the possible role of these EDRPs under shear stress, we examined the effect of physiological shear stress on CNP mRNA expression in endothelial cells derived from the human umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increase). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm2, 2.5-fold increase of static; 15 dyne/cm2, 4.5-fold increase). Increased CNP secretion was also confirmed by the specific radioimmunoassay for CNP. Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, 1.2-fold increase of static: 24 hours, threefold increase) and shear stress intensity-dependent manner (15 dyne/cm2, threefold increase compared with that at 5 dyne/cm2). These results suggest that the coordinated augmentation of mRNA expression of these novel EDRPs may constitute shear stress-dependent vasodilator and antiproliferative effects.
Hypertension 1997 Jun
PMID:Shear stress augments expression of C-type natriuretic peptide and adrenomedullin. 918 Jun 32

Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.
Hypertension 1997 Sep
PMID:Pressure natriuresis after adrenomedullin in anesthetized spontaneously hypertensive rats. 932

Rat adrenomedullin is a peptide vasodepressor that may be of importance in the pathogenesis of hypertensive disease. Because of the known link between obesity and hypertension, we hypothesized that decreased responsiveness to adrenomedullin might be seen in an obese rodent model. In this study, the in vivo vasodilator actions of exogenous adrenomedullin were compared in anesthetized lean (n = 7) and obese (fa/fa) Zucker rats (n = 8). Adrenomedullin dose dependently lowered mean arterial pressure in both phenotypes, but the half-maximal dose (ID50) was 2-fold higher in fa/fa rats (1.7 +/- 0.22 vs. 0.83 +/- 0.06 nmol/kg). Moreover, the duration of effect was markedly reduced in the fa/fa rats, to 1-2 min from about 5 min in the lean animals. There was no evidence for an increased rate of degradation of adrenomedullin in the fa/fa rats. Although the rats used in this study were not hypertensive, adrenomedullin had reduced sensitivity and duration of action. The evidence suggests possible defects at the target receptor or altered metabolism of adrenomedullin in obesity.
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PMID:Reduced sensitivity of fa/fa Zucker rats to adrenomedullin. 936 26

Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2+/-0.5 fmol/10(5) cells/48 hours (mean+/-SEM). Angiotensin II (1 micromol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micromol/L significantly reduced the 10(-6) mol/L angiotensin II- and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10(-6) mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10(-6) mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.
Hypertension 1998 Jan
PMID:Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes. 945 53


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