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)

This paper summarizes the results of our recent studies in a group of healthy subjects on the endocrine effects of the new potent opioid peptide, dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), originally isolated from amphibian skin. Intravenous infusion (5.5 microgram/kg/min for 30 min) of dermorphin (D) significantly increased plasma levels of prolactin (PRL), growth hormone (GH), thyrotropin (TSH) and renin activity (PRA), but decreased plasma levels of cortisol. D produced a small decrease in ACTH, and a small increase in plasma aldosterone. Pretreatment with the opioid receptor antagonist naloxone (N) suppressed the PRL and TSH response to D, blunted the D-induced GH and PRA increase, and completely prevented the D-induced plasma cortisol decrease, but enhanced plasma cortisol and ACTH levels. These data indicate that the action of D is mediated through opioid receptors, and are consistent with the conclusion that: (1) D, a new opioid peptide, can stimulate PRL, GH and TSH release in humans; (2) D increases PRA levels, perhaps via activation of the sympathetic nervous system, providing evidence that opioid peptides may exert an influence on renin secretion; (3) D suppresses plasma cortisol levels, by affecting ACTH secretion, corroborating previous observations that opioid peptides might affect the function of the pituitary-adrenocortical axis.
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PMID:The effects of dermorphin on the endocrine system in man. 300 18

This study was designed to investigate the effect of dermorphin (D), a new synthetic potent opiate-like peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on PRA, plasma aldosterone (PA), plasma cortisol (PC), and plasma ACTH levels in normal men. D infusion (5.5 micrograms/kg X min for 30 min) significantly increased PRA (P less than 0.01) and decreased PC levels (P less than 0.02). D produced a small decrease in ACTH and a small increase in PA. Pretreatment with the opioid receptor antagonist naloxone (N) blunted the D-induced PRA increase and completely prevented the D-induced PC decrease, but enhanced PC and ACTH levels. These data indicate that the action of D is mediated through opioid receptors, and are consistent with the conclusion that 1) D, a new opioid peptide, increases PRA levels, perhaps via activation of the sympathetic nervous system, providing evidence that opioid peptides may exert an influence on renin secretion; and 2) D suppresses PC levels, perhaps by affecting ACTH secretion, corroborating previous observations that opioid peptides might affect the function of the pituitary-adrenocortical axis.
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PMID:Responses of plasma renin activity, aldosterone, adrenocorticotropin, and cortisol to dermorphin, a new synthetic potent opiate-like peptide, in man. 631 31

Haemolytic-uremic syndrome (HUS) is the leading cause of acute renal failure in the childhood. It is characterised by microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure and injury of the renal microvascular endothelium. In HUS the condition of proteolytic kallikrein-kinin system is unknown. The renal KKS seems to participate in the regulation of blood pressure, control of sodium and water excretion, renal vascular resistance and renin release. In this study the role kallikrein in the developing HUS was studied. The general activity of kallikrein in plasma and urine was determined by trypsin-like peptidohydrolase activity (TP), which was measured using substrate Z-D-Ala-Leu-Arg-pNa. Chymotrypsin-like protease activity (ChP) was measured using substrate Glp-Ala-Ala-Leu-pNa. Clinical data were analysed on 60 pediatric patients with HUS, 29 girls and 31 boys, ranging in the age from 3 months to 11 years. TP and ChP levels were determined in different periods of HUS (anuria, diuresis beginning, polyuria, recovery) in serum and urine. In acute phase TP and ChP activities increased significantly. In diuresis recovery serum TP activity was higher, but urine TP level became normal. In dynamic serum and urine ChP levels had tendency to decrease. The present work showed that TP and ChP levels demonstrated activity of pathological renal process and condition of glomerules.
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PMID:[Serine proteinase activity in children with hemolytic-uremic syndrome]. 970 32

The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1-7) to angiotensin-(1-5) and can lead to elevation of angiotensin-(1-7) levels in plasma and tissue. In animal models, angiotensin-(1-7) itself causes or enhances vasodilation and inhibits vascular contractions to angiotensin II. The function of angiotensin-(1-5) is unknown. We investigated whether angiotensin-(1-7) and angiotensin-(1-5) inhibit ACE or antagonize angiotensin-induced vasoconstrictions in humans. ACE activity in plasma and atrial tissue was inhibited by angiotensin-(1-7) up to 100%, with an IC(50) of 3.0 and 4.0 micromol/L, respectively. In human internal mammary arteries, contractions induced by angiotensin I and II and the non-ACE-specific substrate [Pro(11),D-Ala(12)]-angiotensin I were antagonized by angiotensin-(1-7) (10(-5) mol/L) in a noncompetitive way, with a 60% inhibition of the maximal response to angiotensin II. Contractions to ACE-specific substrate [Pro(10)]-angiotensin I were also inhibited, an effect only partly accounted for by antagonism of angiotensin II. Angiotensin-(1-5) inhibited plasma ACE activity with a potency equal to that of angiotensin I but had no effect on arterial contractions. In conclusion, angiotensin-(1-7) blocks angiotensin II-induced vasoconstriction and inhibits ACE in human cardiovascular tissues. Angiotensin-(1-5) only inhibits ACE. These results show that angiotensin-(1-7) may be an important modulator of the human renin-angiotensin system.
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PMID:Angiotensin-(1-7) is a modulator of the human renin-angiotensin system. 1045 57

The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin system. The present study was designed to characterize the role of endothelium in relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine middle cerebral arteries were suspended in organ chambers for isometric force recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP, 3x10(-6) to 10(-5) mol/l), angiotensin-(1-7) (10(-9) to 3x10(-5) mol/l) caused concentration-dependent relaxations in arteries with endothelium, but not in endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation of cGMP. Nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 3x10(-4) mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-[1,2, 4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ, 3x10(-6) mol/l), abolished angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan (10(-5) mol/l), PD 123319 (10(-5) mol/l), [Sar(1),Thr(8)]-angiotensin II (10(-5) mol/l) [Sar(1),Val(5), Ala(8)]-angiotensin II (10(-5) mol/l) or [7-D-Ala]-angiotensin 1-7 (10(-6) mol/l) did not affect these relaxations. However, angiotensin-converting enzyme inhibitor, captopril (10(-5) mol/l) augmented relaxations to angiotensin-(1-7). Finally, bradykinin B(2) receptor antagonist, [D-Arg(0),Hyp(3),Thi(5),D-Tic(7), Oic(8)]-bradykinin (HOE 140, 5x10(-8) mol/l) significantly reduced the effect of angiotensin-(1-7), while bradykinin B(1) receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin (6x10(-9) mol/l) did not influence the vascular response to the heptapeptide. These findings indicate that (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by the release of nitric oxide from endothelial cells, (2) angiotensin receptors do not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this effect appears to be dependent on activation of local production of kinins. Our studies support the concept that angiotensin-(1-7), as a natural vasodilator hormone, may counterbalance the hemodynamic actions of angiotensin II.
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PMID:Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery. 1091 12

We exposed 63 adult spontaneously hypertensive rats (SHR) and 10 (mRen-2)27 transgenic hypertensive rats to a 12-day regimen of either a normal diet (0.5%) or a low-salt diet (0.05%) to evaluate the hypothesis that the vasodepressor heptapeptide, angiotensin-(1-7) [Ang-(1-7)], buffers the pressor effects of angiotensin II during endogenous stimulation of the renin-angiotensin system. Catheters were inserted into a carotid artery and jugular vein under light anesthesia the day before the experiment. Separate groups of conscious instrumented SHR were given short-term infusions of an affinity-purified monoclonal Ang-(1-7) antibody or the neprilysin inhibitor SCH 39370. In addition, SHR and (mRen-2)27 rats were given the Ang-(1-7) receptor antagonist [D-Ala(7)]Ang-(1-7). Exposure to the low-salt diet increased plasma renin activity and elevated plasma levels of angiotensin I and angiotensin II in SHR by 81% and 68%, respectively, above values determined in SHR fed a normal salt diet. Concentrations of angiotensin I and angiotensin II were also higher in the kidney of salt-depleted SHR, whereas plasma and renal tissue levels of Ang-(1-7) were unchanged. Infusion of the Ang-(1-7) antibody produced dose-dependent pressor and tachycardic responses in salt-depleted SHR but no effect in SHR maintained on a normal-salt diet. A comparable cardiovascular response was produced in salt-depleted SHR given either SCH 39370 or [D-Ala(7)]Ang-(1-7). These agents had negligible effects on SHR fed a normal-salt diet. Blockade of Ang-(1-7) receptors produced a similar cardiovascular response in (mRen-2)27 transgenic hypertensive rats fed a low-salt diet. Injections of the heat-inactivated antibody or the subsequent infusion of the antibody to rats given [D-Ala(7)]Ang-(1-7) produced no additional effects. The data support the hypothesis that the hemodynamic effects of neurohormonal activation after salt restriction stimulate a tonic depressor action of Ang-(1-7).
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PMID:Contribution of angiotensin-(1-7) to blood pressure regulation in salt-depleted hypertensive rats. 1098 75

In the adult animal, ANG-(1-7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1-7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers (n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1-7), and ANG II were 86 +/- 21, 13 +/- 2, and 14 +/- 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 +/- 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1-7) (2.9 +/- 0.6 fmol/ml), whereas ANG II concentrations were not different (10 +/- 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 +/- 1.1 pmol ANG I x ml(-1) x h(-1)) than in the ewe (0.9 +/- 0.2 pmol x ml(-1) x h(-1), P < 0.05). Infusion of ANG-(1-7) (approximately 9 microg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1-7) reaching a maximum of 448 +/- 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days (n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1-7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT(1) receptor, and AT(2) receptor were elevated in kidneys of fetuses that received infusions of ANG-(1-7). Infusion of an ANG-(1-7) antagonist ([D-Ala(7)]-ANG-(1-7), 20 microg/h) for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1-7) may play a role in the fetal kidney.
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PMID:Angiotensin-(1--7) in the ovine fetus. 1120 68

Angiotensin-(1-7) [ANG-(1-7)], an endogenous bioactive peptide constituent of the renin-angiotensin system, acts as an inhibitory growth factor in vitro and in vivo. In this study, we evaluated whether the antiangiogenic effect of ANG-(1-7) in the mouse sponge model of angiogenesis might be receptor mediated and involved in the release of nitric oxide (NO). The hemoglobin content (microg/mg wet tissue) of 7-day-old sponge implants was used as an index of the vascularization and showed that daily injections of ANG-(1-7) (20 ng) inhibited significantly the angiogenesis in the implants relative to the saline-treated group. The specific receptor antagonist D-Ala(7)-ANG-(1-7); A-779 prevented ANG-(1-7)-induced inhibition of angiogenesis. The antiangiogenic effect was also abolished by pretreatment with NO synthase inhibitors aminoguanidine (1 mg/ml) or N(G)-nitro-L-arginine methyl ester (0.3 mg/ml). Selective AT1 and AT2 angiotensin-receptor antagonists and an angiotensin-converting enzyme inhibitor, in combination with ANG-(1-7) or alone, did not alter angiogenesis in the implants. These results establish that the regulation of the vascular tissue growth by ANG-(1-7) is associated with NO release by activation of an angiotensin receptor distinct from AT1 and AT2.
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PMID:Mechanisms of angiotensin-(1-7)-induced inhibition of angiogenesis. 1124 19

To determine the effects of physiological alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity (RSNA) and its arterial baroreflex regulation, angiotensin II type 1 receptor antagonists were microinjected into the rostral ventrolateral medulla of anesthetized rats consuming a low, normal, or high sodium diet that were instrumented for simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was increased in rats fed a low sodium diet and decreased in those fed a high sodium diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not mean arterial pressure) dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a high sodium diet. Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and RSNA dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin-(1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower level of arterial pressure, and in rats with congestive heart failure, candesartan increased the arterial baroreflex gain of RSNA. Physiological alterations in the endogenous activity of the renin-angiotensin system influence the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors but not to angiotensin-(1-7) receptors.
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PMID:Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla. 1130 12

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system with vasodilator and anti-proliferative properties. Human adenocarcinoma SK-LU-1 and A549 cells as well as non-small lung cancer SK-MES-1 cells were treated with serum in the presence and absence of Ang-(1-7), to determine whether Ang-(1-7) inhibits the growth of lung cancer cells. Ang-(1-7) caused a significant reduction in serum-stimulated growth in all three lung cancer cell lines. Treatment with Ang-(1-7) resulted in both a dose- and time-dependent reduction in serum-stimulated DNA synthesis in all three cell lines, with IC(50)'s in the sub-nanomolar range. The Ang-(1-7) receptor antagonist [D-Ala(7)]-Ang-(1-7) blocked the attenuation of the serum-stimulated DNA synthesis of SK-LU-1 cells by Ang-(1-7), while neither AT(1) nor AT(2) angiotensin receptor subtype antagonists prevented the response to the heptapeptide. MAS mRNA and protein, a receptor for Ang-(1-7), was detected in the three lung cancer cell lines, suggesting that the anti-proliferative effect of Ang-(1-7) in the cancer cells may be mediated by the non-AT(1), non-AT(2), AT((1-7)) receptor MAS. Other angiotensin peptides [Ang I, Ang II, Ang-(2-8), Ang-(3-8) and Ang-(3-7)] did not attenuate mitogen-stimulated DNA synthesis of SK-LU-1 cells, demonstrating that Ang-(1-7) selectively inhibits SK-LU-1 cancer cell growth. Pre-treatment of SK-LU-1 cells with 10 nM Ang-(1-7) reduced serum-stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2, indicating that the anti-proliferative effects may occur, at least in part, through inhibition of the ERK signal transduction pathway. The results of this study suggest that Ang-(1-7) inhibits lung cancer cell growth through the activation of an angiotensin peptide receptor and may represent a novel chemotherapeutic and chemopreventive treatment for lung cancer.
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PMID:Inhibition of human lung cancer cell growth by angiotensin-(1-7). 1528 77


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