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)

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

Circulating angiotensin II (ANG II) has several physiological effects that result from interaction of the peptide with AT1 receptors in the brain. Our purpose was to determine if selective pharmacological blockade of brain AT1 receptors would reverse chronic low-dose ANG II-induced hypertension. Male Sprague-Dawley rats were instrumented with chronic indwelling arterial and venous catheters and a lateral intracerebroventricular (i.c.v.) cannula. All rats received ANG II i.v. for 15 days at a dose of 4 ng.min-1. On days 2, 7 and 12 of the ANG II infusion a bolus of an AT1 receptor antagonist, the active metabolite of losartan, EXP 3174 (1 microgram in 2 microliters of saline, i.c.v.; n = 5) or vehicle (2 microliters of saline; n = 2) was administered into the cerebrospinal fluid. Mean arterial pressure and heart rate were measured at numerous time points after this injection. Although the dose of EXP 3174 used in preliminary experiments was shown to block the responses to i.c.v. ANG II this treatment did not lower MAP in chronic ANG II-hypertension. These results suggested that either ANG II-hypertension does not involve brain AT1 receptors, or that i.c.v. EXP 3174 may not gain access to brain sites at which circulating ANG II acts to produce hypertension. To test this latter possibility ANG II was microinjected into the area postrema of anesthetized rats. The area postrema is one of several circumventricular organs at which circulating ANG II may act to influence arterial pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cerebroventricular injection of angiotensin II antagonist: effects on blood pressure responses to central and systemic angiotensin II. 775 62

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 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

The function of the recently discovered angiotensin II type 2 (AT2) receptor remains elusive. This receptor is expressed abundantly in fetus, but scantily in adult tissues except brain, adrenal medulla, and atretic ovary. In this study, we demonstrated that this receptor mediates programmed cell death (apoptosis). We observed this effect in PC12W cells (rat pheochromocytoma cell line) and R3T3 cells (mouse fibroblast cell line), which express abundant AT2 receptor but not AT1 receptor. The cellular mechanism appears to involve the dephosphorylation of mitogen-activated protein kinase (MAP kinase). Vanadate, a protein-tyrosine-phosphatase inhibitor, attenuated the dephosphorylation of MAP kinases by the AT2 receptor and restored the apoptotic changes. Antisense oligonucleotide to MAP kinase phosphatase 1 inhibited the AT2 receptor-mediated MAP kinase dephosphorylation and blocked the AT2 receptor-mediated apoptosis. These results suggest that protein-tyrosine-phosphatase, including MAP kinase phosphatase 1 activated by the AT2 receptor, is involved in apoptosis. We hypothesize that this apoptotic function of the AT2 receptor may play an important role in developmental biology and pathophysiology.
 ...
PMID:Angiotensin II type 2 receptor mediates programmed cell death. 855 95

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

KT3-671, a nonpeptide AT1 receptor antagonist, was administered to 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) daily for 3 weeks. Its effects on systolic, mean, and diastolic arterial blood pressure (SAP, MAP, DAP), heart rate and locomotor activity were investigated with radiotelemetry. A clear diurnal variation in blood pressure, heart rate, and locomotor activity was observed in synchrony with the light cycle. KT3-671 at a daily dose of 10 mg/kg orally (p.o), produced a significant and consistent reduction in blood pressure, preventing the development of hypertension. KT3-671 reduced SAP more than DAP, suggesting that it may affect both vascular tone and cardiac output. Although KT3-671 did not affect diurnal rhythms in heart rate and locomotor activity, it did cause a slight but significant reduction in heart rate. The MAP determined 23 h after the administration of KT3-671 showed a significant reduction from the day 2 of therapy to the day 3 after discontinuation of therapy, suggesting a long duration of antihypertensive action. There was no rebound increase in blood pressure after discontinuation of KT3-671 therapy. These results suggest that KT3-671 may be potentially useful in the therapy of hypertension.
 ...
PMID:Effect of repeated administration of KT3-671, a nonpeptide AT1 receptor antagonist, on diurnal variation in blood pressure, heart rate, and locomotor activity in stroke-prone spontaneously hypertensive rats as determined by radiotelemetry. 890 3

YM358 2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[ 1,5-b][1,2,4]-triazole potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated by using radiotelemetry. A clear diurnal variation in blood pressure, heart rate and locomotor activity was observed in synchrony with the light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood pressure in a dose-dependent manner. Although a mild attenuation of the antihypertensive effect of YM358 was observed during the early stage of therapy, YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr MAP and DAP, and it prevented the further development of hypertension. YM358 did not affect either heart rate or locomotor activity or their diurnal variations. After the discontinuation of therapy with YM358, the blood pressure recovered promptly to the control level while there was no sign of a rebound increase in blood pressure. These results suggest that YM358 may be potentially useful for the treatment of hypertension.
 ...
PMID:Antihypertensive effect of repeatedly administered YM358, an angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats. 903 37

Low sodium intake has been demonstrated to upregulate the gene expression of the predominant renal type 1 angiotensin II (Ang II) receptor (AT1), the AT1A subtype. The study presented here tests the hypothesis that the upregulation of renal AT1 mRNA induced by sodium depletion occurs conjointly with an elevation of the AT1 receptor that modulates renal growth. Seven-week-old male Wistar rats were divided into four groups and treated for 2 wk with normal sodium diet, normal sodium diet plus 3 mg/kg/day losartan, low sodium diet, or low sodium diet plus losartan. Body weight and MAP were not significantly different among the four groups. Plasma renin activity was significantly elevated by losartan treatment, low salt intake, or a combination of the two, compared with the plasma renin activity of the controls. Northern blot analysis indicated that renal AT1 mRNA levels were significantly increased-183% by losartan, 212% by low salt intake, and 227% by the combination of the two-compared with their levels in controls. Radioligand binding assays revealed that AT1 receptors were significantly increased by low salt intake but were significantly decreased by losartan treatment. Renal AT1 receptor binding in the rats subjected to sodium depletion plus losartan did not differ from that in control rats. Kidney weight, kidney weight/body weight ratio, and renal DNA and protein content were not altered by sodium depletion but were significantly lowered by losartan treatment with both normal and low sodium intake, compared with those of controls. The protein/DNA ratio was not significantly different among the four groups. Blockade of renal AT1 receptors with losartan was found to retard normal renal growth, indicating that Ang II is required for normal renal development. Low sodium intake was found to increase mRNA and expression of the renal AT1 receptor but to have no effect on renal growth, suggesting that an increase in renal mass above a normal level requires the activation of multiple factors. Blockade of the AT1 receptor by losartan was found to upregulate AT1 mRNA but to down-regulate the AT1 receptor, suggesting that AT1 receptor-mediated intracellular events are necessary to sustain functional AT1 receptor expression in the kidney.
 ...
PMID:Regulation of angiotensin type 1 receptor and its gene expression: role in renal growth. 904 37

In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.
 ...
PMID:Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats. 909 57


1 2 3 4 Next >>