Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminopeptidase M (EC 3.4.11.2), an enzyme present on the cell surface of vascular endothelium and/or smooth muscle, rapidly hydrolyzes leucyl- and arginyl-2-naphthylamides and a number of vasoactive peptides at physiologic pH. Utilizing both thin-layer chromatography and high pressure liquid chromatography, it was found that vascular aminopeptidase M converted kallidin to bradykinin and inactivated des(Asp1)angiotensin I, angiotensin III, hepta(5-11)substance P and hexa(6-11)substance P. Aminopeptidase M did not, however, hydrolyze bradykinin, angiotensin I, angiotensin II, saralasin, vasopressin, oxytocin or any form of substance P containing a component of the Arg-Pro-Lys-Pro sequence. Both the naphthylamidase and peptidase activities were inhibited similarly by known amino-peptidase M inhibitors including o-phenanthroline, amastatin, bestatin and puromycin. However, inhibitors of angiotensin I converting enzyme (captopril), carboxypeptidase N (MERGETPA), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme and dipeptidyl(amino)peptidase IV (diisopropylphosphofluoridate, DFP) were without effect. These results demonstrate that vascular, cell surface aminopeptidase M can selectively metabolize vasoactive peptides and may play a role in modulating their levels in the circulation and/or within the vessel wall.
 ...
PMID:Vascular, plasma membrane aminopeptidase M. Metabolism of vasoactive peptides. 240 81

Patients with untreated essential hypertension had significantly higher plasma atrial natriuretic factor (ANF) levels (92.9 +/- 12.9 pg/ml, mean +/- SE) than those of age-matched controls (37.8 +/- 6.0 pg/ml; p less than 0.01). Plasma ANF levels in essential hypertensive patients showed a significant positive correlation with mean arterial pressure (MAP; r = 0.46, p less than 0.05) and an inverse correlation with plasma renin activity (PRA; r = -0.43, p less than 0.05). Plasma ANF levels after medication showed significant correlation with the decrease in MAP (r = 0.565, p less than 0.05). Patients with primary aldosteronism had significantly higher plasma ANF levels (122.4 +/- 30.2 pg/ml, n = 8) than those of controls (p less than 0.05). The levels returned to normal after extirpation of adrenal tumors. The response of plasma ANF levels in patients with primary aldosteronism to volume expansion with infusion of 2 L of physiological saline in 2 hours was greater than in controls. Such exaggerated response disappeared after surgical treatment. Infusion of angiotensin II (Ang II; 20 ng/kg/min) or norepinephrine (200 ng/kg/min) for 30 minutes to normal volunteers (n = 5) resulted in a rise in MAP (24.9 +/- 3.3 and 15.8 +/- 4.4 mm Hg, respectively) and a twofold increase in plasma ANF level. Infusion of the Ang II antagonist [Sar1, Ile8]Ang II (600 ng/kg/min) for 30 minutes, resulted in a rise in MAP (18.8 +/- 2.1 mm Hg) and more than a twofold increase in plasma ANF level in patients with essential hypertension (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Atrial natriuretic factor in essential hypertension and adrenal disorders. 296 1

Intracellular signaling pathways regulating vascular smooth muscle (VSM) cell growth and hypertrophy can be initiated by activation of receptor tyrosine kinases and/or protein kinase C (PKC). Mitogen-activated protein kinases (MAP kinases) are cytosolic serine/threonine kinases, proposed to act as a point of convergence for diverse growth factors utilizing these signaling pathways. The goals of this study were (1) to determine whether MAP kinase is expressed in cultured rat aortic VSM, (2) to assess the activation of MAP kinase by known proliferative and hypertrophic stimuli, and (3) to determine if stimulation of a PKC-dependent signaling pathway in these cells results in MAP kinase activation. MAP kinase activity was measured in cytosolic extracts of aortic VSM by quantifying myelin basic protein phosphorylation. Three peaks of activity were resolved chromatographically and identified as MAP kinase isoforms (MW 42, 44, and 46 kDa) by immunoblotting with antipeptide antibodies specific for MAP kinase. MAP kinase activity in quiescent growth-arrested cells (157 +/- 19 pmole 32P/min/mg) was markedly stimulated within 15 min by known mitogens (10% serum, 731 +/- 40 pmole 32P/min/mg; 40 ng/ml PDGF, 670 +/- 105 pmole 32P/min/mg; P < 0.01) and partially sustained for at least 90 min (serum, 606 +/- 34 pmole 32P/min/mg; PDGF, 323 +/- 59 pmole 32P/min/mg P < 0.05). Angiotensin II (AII, 0.1 microM) and a pharmacological PKC activator, phorbol 12,13-dibutyrate (PDB, 0.1 microM), are reported to be nonmitogenic hypertrophic stimuli in these cells. These stimuli transiently increased MAP kinase activity with a peak at 5 min (AII, 328 +/- 15 pmole 32P/min/mg; PDB, 592 +/- 41 pmole 32P/min/mg; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of MAP kinase activity by growth stimuli in vascular smooth muscle. 804 Nov 41

Pressor doses of angiotensin II induced haemodilution in goats despite renal fluid losses. This study was undertaken to determine if this response is dose-dependent and correlated to the vasoconstrictor action of angiotensin II. Angiotensin II at the doses 0.025, 0.05 and 0.1 micrograms min-1 was given intravenously to five goats. Mean arterial blood pressure increased by 3, 10 and 20 mmHg, respectively, and the renal Na excretion rose. The haematocrit decreased by 7, 10, and 9% (percentage of control values) and the plasma protein concentration by 1% (n.s.), 4.5, and 3.5%, respectively. Infusions of phenylephrine (40 micrograms min-1; n = 6) caused an equivalent increase of blood pressure and renal Na excretion as angiotensin II (0.1 micrograms min-1), but the haematocrit increased by 16% and the plasma protein concentration by 6.5%. Infusions of atrial natriuretic peptide (1 microgram min-1) alone or together with angiotensin II (0.1 microgram min-1), or phenylephrine were also given (n = 6). Infusions of atrial natriuretic peptide alone did not change blood pressure, but renal Na excretion increased. The haematocrit rose by 10.5% and the plasma protein concentration by 7.6%. Adding atrial natriuretic peptide to the angiotensin II solution attenuated the rise of MAP and counteracted the haemodilution, but did not decrease the natriuresis. Infusions of phenylephrine plus atrial natriuretic peptide caused similar elevations of blood pressure and renal Na excretion as phenylephrine alone. The haematocrit rose by 24% and the plasma protein concentration by 13%. These results show that in the intact conscious goat rapid and marked changes in haematocrit and plasma protein concentration can be provoked by intravenous infusions of vasoactive agents and that these effects are not correlated to changes in arterial blood pressure or renal Na excretion.
 ...
PMID:Discrepant effects of angiotensin II and phenylephrine on plasma volume in conscious goats. 804 38

1. The feedback control of arterial blood pressure by the kidney in the range of hours was investigated in resting, conscious foxhounds. 2. A servo-control device (connected to an aortic occlusive cuff implanted above both renal arteries) was used to maintain a constant pressure difference of 20 mmHg between aortic pressure measured proximal (mean arterial blood pressure: MAP) and distal (renal artery pressure: RAP) to the aortic cuff. 3. Protocol 1 (n = 6) served as a 4 h time control without intervention, protocol 2 (n = 6) consisted of three periods: after a control of 20 min duration, the servo-control device was activated for 180 min; this was followed by a recovery period of 40 min. Protocol 3 (n = 6) was as protocol 2, but during converting-enzyme inhibition. 4. Servo-control increased plasma renin activity (PRA) transiently from 0.5 ng angiotensin I (AI) ml-1 h-1 to a peak value of 2.4 ng AI ml-1 h-1, subsequently both RAP and MAP rose to reach a new steady state. During this increase in RAP, PRA declined to 1.4 ng AI ml-1 h-1. 5. On average, the compensation of the pressure decrease sensed by the kidney amounted to 63% of the error signal (closed-loop gain of 0.63 +/- 0.1). 6. Converting-enzyme inhibition reduced this closed-loop gain significantly (protocol 2 vs. protocol 3, 0.63 +/- 0.1 vs. 0.15 +/- 0.1; P < 0.05). 7. It is concluded, that the kidney plays an important role in medium-term blood pressure regulation, most probably via the renin-angiotensin system.
 ...
PMID:The role of the kidney in canine blood pressure control: direct assessment of the closed-loop gain. 822 94

Angiotensin(1-7) had a compound effect on blood pressure of pithed Sprague-Dawley rats. The initial phase of the response consisted of an increase in MAP of short duration and independent of injected dose, followed by a decline of arterial pressure to values below baseline. Both the magnitude (range: -4 +/- 1 to -13 +/- 1 mmHg) and the duration (range: 83 +/- 13 to 255 +/- 17 s) of the depressor response correlated with the dose of peptide. Indomethacin (5 mg/kg) eliminated the depressor component. Only [Sar1,Thr8]Ang II inhibited the effect of Ang(1-7) completely. We conclude that angiotensin(1-7) possesses myotonic actions that are in part related to release of vasodilator prostaglandins through an angiotensin receptor other than AT1 or AT2.
 ...
PMID:Cardiovascular actions of angiotensin(1-7). 823 10

The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.
 ...
PMID:Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs. 834 91

The effect of 24-hour unilateral ureteral obstruction (UUO) on the expression and regulation of the renin-angiotensin system (RAS) in rats and of pretreatment with lisinopril (5 mg/kg/day) or the AT1-R inhibitor, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lowered MAP, and normalized eicosanoid excretion by the POK. Cortex and medulla POK:CK ratio of relative density R mRNA was approximately 3.5 for both. Sham, POK, and CK showed renin immunoreactivity and R mRNA exclusively in juxtaglomerular position. In addition, in POK renin was expressed in mesangial cells, along greater lengths of afferent arterioles and in dilated distal tubules and loops of Henle. In situ hybridization revealed that approximately 20% more glomeruli in POK than CK overexpressed R mRNA. Blood vessels of POK consistently showed greater ACE and Ao mRNA expression than CK. Overexpression of the genes coding for members of the RAS is possibly responsible for local Ang II production which, in view of the response to CEI and AT1-R inhibitors, is at least partly responsible for the severe hemodynamic changes in UUO.
 ...
PMID:Regulation of renin-angiotensin system in unilateral ureteral obstruction. 839 17

Angiotensin II (Ang II) has growth promoting effects in a number of cells and tissues in vitro. The purpose of this study was to examine the in vivo effect of Ang II on the renal expression of the early growth response genes c-fos, Egr-1 and c-jun. Adult male rats underwent two basal 30 minute clearance periods during which the normal saline vehicle was infused into the left renal artery. Normal saline, Ang II (50 ng/kg/min), or Ang II plus the Ang II antagonist Sar1 Gly8-angiotensin II (10 micrograms/kg/min) were then selectively infused into the left renal artery for two additional 30 minute periods. MAP was similar during basal and Ang II infusion. Hemodynamic effects (decrease in GFR and RPF and increase in renal vascular resistance) were observed only in the Ang II-infused left kidney allowing the right kidney to serve as a paired control for the effects of anesthesia and surgery. Significant increases in the expression of the early growth response genes Egr-1 and c-fos, but not c-jun, were found in the Ang II-infused left kidney compared to the control right kidney. The simultaneous infusion of Ang II (50 ng/kg/min) and the Ang II antagonist Sar1 Gly8-angiotensin II (10 micrograms/kg/min) blocked the increase in Egr-1 and c-fos expression, demonstrating the specificity of the response to Ang II. To compare the effect of another renal vasoconstrictor on the expression of early growth response genes, norepinephrine (40 ng/kg/min) was infused into the left renal artery.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of angiotensin II and norepinephrine on early growth response genes in the rat kidney. 845 58

Although many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in development of cardiac hypertrophy, the mechanism by which Ang II increases protein synthesis in cardiac myocytes remains unclear. It has been reported that the phosphorylation of S6 protein in 40 S ribosome is correlated to the efficiency of protein synthesis. In the present study, we have examined whether Ang II activates p70 S6 kinase (p70S6K), which has been reported to phosphorylate S6 protein. Ang II activated p70S6K through AT1 receptor. An immunosuppressant agent, rapamycin, inhibited Ang II-induced p70S6K activation but not the activation of MAP kinases or the induction of c-fos gene expression. Rapamycin also abolished Ang II-induced increase in protein synthesis. These results suggest that Ang II induces cardiac hypertrophy by activating p70S6K.
 ...
PMID:Activation of p70 S6 protein kinase is necessary for angiotensin II-induced hypertrophy in neonatal rat cardiac myocytes. 860 1


1 2 3 4 5 6 Next >>