UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocardial cells, like endothelial cells, release nitric oxide (NO) and may play a role in modulating the contractility of cardiac muscle. We have studied the effects of NG-nitro-L-arginine methyl ester (L-NAME), a selective NO synthase inhibitor, on basal and volume expansion-induced secretion of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in vivo. In conscious chronically cannulated rats, bolus injection of L-NAME at doses of 1, 3, and 10 mg/kg, iv, caused a dose-dependent increase in mean arterial pressure and sustained bradycardia, whereas right atrial pressure remained unchanged. The hemodynamic effects of L-NAME were reversed by simultaneous administration of L-arginine, a precursor of NO. Administration of 3 and 10 mg/kg L-NAME alone increased plasma levels of immunoreactive ANP (IR-ANP) from 30 +/- 5 to 52 +/- 9 pmol/liter and from 38 +/- 6 to 91 +/- 16 pmol/liter (P < 0.01), respectively, but had no effect on plasma levels of immunoreactive BNP (IR-BNP). The increase in plasma IR-ANP concentration in response to L-NAME infusions showed a positive linear correlation (P < 0.01) with the increase in mean arterial pressure and a negative correlation (P < 0.01) with the changes in heart rate. Acute volume expansion with 0.9% saline in conscious animals resulted in a 3.2-fold increase in plasma IR-ANP levels (from 35 +/- 7 to 113 +/- 15 pmol/liter; P < 0.01), but plasma IR-BNP levels did not change. In the rats pretreated with L-NAME, the relation between the changes from control in plasma IR-ANP and right atrial pressure shifted to the left; the absolute increases corresponding to the 3 mm Hg increase in right atrial pressure were 66 +/- 13, 76 +/- 15, 135 +/- 33, and 148 +/- 24 pmol/liter in the control and 1 mg/kg L-NAME, 3 mg/kg L-NAME-, and 10 mg/kg L-NAME-treated groups, respectively. The combined infusion of L-NAME and L-arginine attenuated the L-NAME-induced increase in ANP release. Our results show that L-NAME increases basal plasma IR-ANP levels and enhances stretch-induced ANP release, suggesting that secretion of ANP in response to volume load may be modulated by the locally released nitric oxide from the endothelium. Further, acute regulation of BNP secretion in response to inhibition of nitric oxide synthase and volume load differs from that of ANP.
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PMID:Role of nitric oxide on cardiac hormone secretion: effect of NG-nitro-L-arginine methyl ester on atrial natriuretic peptide and brain natriuretic peptide release. 786 78

Under physiological conditions, the endocrine heart contributes to the maintenance of cardiovascular homeostasis through the polypeptide hormones ANF and BNP, which are members of the natriuretic peptide (NP) family. Given that NPs are of interest from the basic and clinical points of view, the genetic expression and secretion of ANF and BNP as well as the nature of the interaction of these hormones with their receptors has been the subject of extensive studies since the discovery of ANF in 1980. Following hemodynamic overload, increased secretion of NPs by the heart can be seen. This change may occur without an increase in gene expression as observed for atrial NPs following acute volume expansion, or it can occur with an increase in both ANF and BNP gene expression in atria only as seen in mineralocorticoid escape during which it is obvious that a critical decrease in hormone stores must be reached before transcriptional activation occurs. Chronic hemodynamic pressure or volume overload results in increased expression of NPs in atria and ventricles. Under these circumstances, the increased production of BNP by hypertrophic ventricles changes the normal plasma concentration ratio of ANF to BNP, a fact that has clinical diagnostic and prognostic implications. There are exceptions to this rule: chronic, severe L-NAME hypertension, which may occur without left ventricular hypertrophy, does not cause this effect and increased ventricular NP gene expression can occur in mineralocorticoid hypertension before detectable ventricular hypertrophy. Atrial and ventricular NP gene expression appears to be under different transcriptional control because pharmacological treatments such as chronic ACE inhibition or ET(A) receptor blockade can reverse the increased ventricular NP expression but has no detectable effect on atrial NP gene expression. This is not unlike the myosin heavy chain switch that is observed in certain pathologies, and can be pharmacologically reversed in a manner similar to NPs in the ventricles but it does not occur in atrial muscle. These observations made in vivo or using isolated adult atria often differ strikingly from results obtained using the mixed phenotype afforded by cardiocytes in culture, indicating that the kinds of questions addressed by each approach must be judiciously chosen. G-protein coupled receptor-mediated actions of neurohumors such as endothelin and phenylephrine are normally used to stimulate NP gene expression and release in different in vitro models. The main physiological stimulus for increased ANF release, atrial muscle stretch, also appears to rely on G-protein-coupled mechanisms. Alternative agonists and receptor types at play are suggested by the finding that circulating levels of BNP are selectively increased before and during overt cardiac allograft rejection episodes in human patients. The data suggest that enhanced BNP plasma levels could form a basis for a noninvasive test for cardiac allograft rejection. However, the molecular mechanism by which expression of NPs are regulated in the transplanted heart is not well understood. Conditioned medium from mixed lymphocyte reaction cultures, considered an in vitro model of transplantation immunity, induces specific upregulation of BNP as do individual pro-inflammatory cytokines. Findings such as these suggest that the study of NPs will continue to produce a wealth of information relevant to basic and clinical scientists.
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PMID:The physiological and pathophysiological modulation of the endocrine function of the heart. 1155 79

1. The aim of the present study was to determine whether the regulation of vascular natriuretic peptide receptors (NPR) is related to the local renin-angiotensin system (RAS). 2. Male Sprague-Dawley rats were made two-kidney, one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive to activate and inhibit the RAS, respectively. Another model of hypertension was induced by treatment with an inhibitor of nitric oxide synthesis, namely NG-nitro-L-arginine methyl ester (L-NAME). 3. The mRNA expression of NPR-A, NPR-C, angiotensin- converting enzyme (ACE) and angiotensin AT1 receptors was determined in the thoracic aorta by semiquantitative reverse transcription-polymerase chain reaction. The particulate guanylyl cyclase activity stimulated by atrial natriuretic peptide (ANP) was also determined in the membrane fraction of the thoracic aorta. 4. The plasma concentrations of ANP were increased significantly in the three models of hypertension. Plasma renin activity was increased in 2K1C hypertension, decreased in DOCA-salt hypertension and not significantly altered in L-NAME hypertension. 5. The mRNA expression of NPR-A and NPR-C was decreased, whereas that of ACE and AT1 receptors was increased in 2K1C and L-NAME hypertension. The mRNA expression of NPR-A and NPR-C was increased, whereas that of ACE and AT1 receptors was decreased in DOCA-salt hypertension. 6. The particulate guanylyl cyclase activity was decreased in 2K1C and L-NAME hypertension and increased in DOCA-salt hypertension. 7. The vascular expression of NPR may be reciprocally regulated by local RAS activity.
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PMID:Altered expression of vascular natriuretic peptide receptors in experimental hypertensive rats. 1198 39

This study examined the role of angiotensin II in the increase of blood pressure, activation of cardiac natriuretic peptide gene expression, left ventricular hypertrophy, and vascular changes in nitric oxide-deficient hypertension. N(G)-nitro->L-arginine methyl ester (>L-NAME, 20 mg/kg/d), angiotensin II type 1 receptor (AT ) antagonist losartan (20 mg/kg/d), or their combination were administered orally for 8 weeks in Wistar rats. >L-NAME elevated systolic blood pressure, which reached its maximum within 4 weeks (200 +/- 4 mm Hg). Despite hypertension, >L-NAME administration for 8 weeks did not induce left ventricular hypertrophy. Losartan treatment significantly decreased the development of hypertension induced by >L-NAME and decreased left ventricular hypertrophy in untreated rats. In contrast, losartan did not prevent the hypertrophic remodeling of the mesenteric resistance arteries induced by >L-NAME. >L-NAME treatment increased ventricular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels and immunoreactive BNP levels significantly. Losartan therapy decreased the >l-NAME-induced ventricular ANP gene expression by 69% (p < 0.05) and also reduced ventricular BNP mRNA levels so that it did not differ from control. Losartan treatment alone decreased ventricular immunoreactive ANP and BNP levels by 30% (p < 0.05). These results show that ventricular ANP and BNP gene expression are dissociated from the increased ventricular mass in nitric oxide deficiency-induced hypertension. Results suggest that >l-NAME-induced hypertension and the associated activation of ventricular ANP and BNP gene expression are, at least in part, mediated by angiotensin II, whereas the resistance vessel hypertrophy following nitric oxide synthase inhibition is angiotensin II independent.
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PMID:N(G)-nitro-L-arginine methyl ester-induced hypertension and natriuretic peptide gene expression: inhibition by angiotensin II type 1 receptor antagonism. 1219 34

Possible mechanisms for nicotine-induced relaxation were investigated in the isolated sheep's sphincter of Oddi. Sheep's sphincter of Oddi rings were mounted in tissue bath with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. Nicotine (1 x 10(-5) to 3 x 10(-3) mol/L) produced concentration-dependent relaxation on sphincter of Oddi precontracted by carbachol (10(-6) mol/L). Nicotine-induced relaxation was 72.8 +/- 4.2% of precontraction with carbachol (10(-6) mol/L) (mean pD2 value, 3.76 +/- 0.05 mol/L). Nicotine-induced relaxation was not affected by N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) mol/L), methylene blue (10(-5) mol/L), indomethacin (10(-5) mol/L), hexamethonium (10(-5) mol/L), glibenclamide (10(-5) mol/L), 4-aminopyridine (10(-3) mol/L), tetraethylammonium (3 x 10(-4) mol/L), clotrimazole (10(-6) mol/L), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (10(-6) mol/L), and anthracene-9-carboxylate (9-AC) (10(-6) mol/L), but potentiated by bupivacain (10(-5) mol/L). A calcium-antagonizing effect of nicotine was not observed. The results suggest that nicotine-induced relaxation of the sheep's sphincter of Oddi is not mediated by the release of prostaglandins, nitric oxide (NO), or a related substance; by the activation of potassium channels or chloride channels; or by the stimulation of nicotinic cholinoceptors. Potentiation of the nicotine-induced relaxation by bupivacain indicates that blockade of sodium channels may play a role in this relaxation.
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PMID:Investigation of the mechanism of nicotine-induced relaxation on the sheep sphincter of Oddi. 1564 32

Adrenomedullin may provide a compensatory mechanism to attenuate left ventricular hypertrophy (LVH). Nitric oxide synthase inhibition, induced by chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats, induces cardiac hypertrophy in some, but not all cases; there are few reports of direct assessment of cardiomyocyte parameters. The objective was to characterize hypertrophic parameters in left (LV) and right ventricular (RV) cardiomyocytes after administration of L-NAME to rats for 8 wk and to determine whether adrenomedullin and its receptor components were upregulated. After treatment with L-NAME (20 and 50 mg x kg(-1) x day(-1)), compared with nontreated animals, 1) systolic blood pressure increased (by 34.2 and 104.9 mmHg), 2) heart weight-to-body wt ratio increased 24.1% at the higher dose (P < 0.05), 3) cardiomyocyte protein mass increased (P = NS), 4) cardiomyocyte protein synthesis ([14C]phenylalanine incorporation) increased (P < 0.05), 5) expression of skeletal alpha-actin, atrial natriuretic peptide, brain natriuretic peptide, and ET-1 mRNAs was enhanced (P < 0.05) in LV but not RV cardiomyocytes at 20 and 50 mg x kg(-1) x day(-1), respectively, and 6) expression of adrenomedullin, receptor activity-modifying protein 3 (RAMP3), and RAMP2 (but not calcitonin receptor-like receptor and RAMP1) mRNAs was increased by L-NAME (20 mg x kg(-1) x day(-1)) in LV. In conclusion, L-NAME enhanced protein synthesis in both LV and RV cardiomyocytes but elicited a hypertrophic phenotype accompanied by altered expression of the counterregulatory peptide adrenomedullin and receptor components (RAMP2, RAMP3) in LV only, indicating that the former is due to impaired nitric oxide synthesis, whereas the phenotypic changes are due to pressure overload.
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PMID:Upregulation of adrenomedullin and its receptor components during cardiomyocyte hypertrophy induced by chronic inhibition of nitric oxide synthesis in rats. 1604 Jul 21

C-type natriuretic peptide (CNP) is the major natriuretic peptide in the brain and its mRNA has been reported in the central nervous system, which supports local synthesis and its role as a neuromodulator. The aim of the present work was to study the effect of centrally applied CNP on pancreatic secretion. Rats were fitted with a lateral cerebroventricular cannula one-week before secretion studies. The central administration of CNP dose-dependently enhanced pancreatic fluid and protein output. CNP response was diminished by atropine and hexamethonium, but it was abolished by vagotomy. Neither adrenergic antagonists nor the administration of (D-p-Cl-Phe(6),Leu(17))-vasoactive intestinal peptide (VIP antagonist) or N(omega) Nitro-L arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) affected CNP response. The effect induced by CNP was mimicked by 8-Br-cGMP but not by c-ANP-(4-23) amide (selective agonist of the natriuretic peptide receptor C). Furthermore, CNP interacted with cholecystokinin (CCK) and secretin in the brain to modify pancreatic secretion. Present findings show that centrally applied CNP enhanced pancreatic secretion through a vagal pathway and suggest that CNP response is mediated by the activation of natriuretic peptide guanylyl cyclase coupled receptors in the brain.
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PMID:C-type natriuretic peptide applied to the brain enhances exocrine pancreatic secretion through a vagal pathway. 1626 10

Rhizoma polygoni cuspidate, used as a traditional Chinese herb, offered the therapeutic potential for cardiovascular diseases. Resveratrol, extracted from root of the rhizoma polygoni cuspidate has sparked increasing interest in therapeutic application. Resveratrol was shown to exert a variety of pharmacological effects including cardioprotective and cancer chemopreventive properties. However, its mechanisms of the action are not completely understood. The aim of this study was to investigate the molecular mechanism of resveratrol on preventing cardiac fibroblasts from proliferative and hypertrophic response induced by angiotensin II. Cell proliferation and cytotoxicity were detected by methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assay, respectively. Hypertrophic response of cardiac fibroblasts was measured by mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Resveratrol (25, 50, 75, and 100 microM) inhibited cardiac fibroblasts proliferation in a dose- and time-dependent manner compared with angiotensin II group (P<0.01), and the inhibitory effects were blocked by pretreatment with N(G)-nitro-l-arginine methyl ester (L-NAME) and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ). Resveratrol increased nitric oxide (NO) and nitric oxide synthase (NOS) levels in culture medium, increased intracellular cyclic GMP (cGMP) level in cardiac fibroblasts, and decreased ANP and BNP levels in culture medium. The mRNA expression of ANP and BNP was suppressed by resveratrol. These results suggested that resveratrol inhibited cardiac fibroblasts proliferation induced by angiotensin II, and the inhibitory effect might be associated with the activation of NO-cGMP signaling pathway.
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PMID:Resveratrol inhibits proliferation of cultured rat cardiac fibroblasts: correlated with NO-cGMP signaling pathway. 1749 37

Natriuretic peptides are regulatory autacoids in the mammalian myocardium whose functions, mediated via particulate guanylyl cyclase/cGMP, may include cytoprotection against ischaemia-reperfusion injury. Previous work has identified that B-type natriuretic peptide (BNP) limits infarct size when administered prior to and during coronary occlusion through a K(ATP) channel-dependent mechanism. The present study examined the hypothesis that the protection afforded by BNP is mediated specifically at reperfusion in a postconditioning-like manner. Langendorff-perfused rat hearts were subjected to 35 min coronary artery occlusion and 120 min reperfusion, and infarct size was determined by tetrazolium staining. Postconditioning was effected by applying six 10-second periods of global ischaemia at the onset of reperfusion.Treatment with either BNP 10 nM or the NO donor S-nitroso-N-acetylpenicillamine (SNAP) 1-10 microM was commenced 5 min prior to reperfusion and continued until 10 min after reperfusion. Control infarct size (% of ischaemic risk zone) was 40.8 +/- 3.7%.BNP at reperfusion induced a significant limitation of infarct size (BNP 22.9 +/- 4.1% P<0.05 vs. control). Co-treatment at reperfusion with BNP and the K(ATP) channel blockers 5-hydroxydecanote (5HD, 100 microM), glibenclamide (Glib; 10 microM) or HMR1098 (10 microM) abolished the infarct-limiting effect of BNP (BNP + 5HD 41.0 +/- 3.9%, BNP + Glib 39.8 +/- 5.6%, BNP + HMR 1098 46.0 +/- 7.1%,P < 0.05 vs. BNP). BNP given together with L-NAME (100 microM) at reperfusion resulted in a marked loss of protection (BNP + L-NAME 53.1 +/- 3.8% P < 0.001 vs. BNP). In a second series of experiments, SNAP (1-10 microM) given at reperfusion was found not to be protective (SNAP 1 microM 30.2 +/- 4.9%, SNAP 2 microM 27.5 +/- 9.5%, SNAP 5 microM 39.2 +/- 5.7%, SNAP 10 microM 33.7 +/- 6.4%, not significant vs. control). In a third series of experiments, postconditioning significantly limited infarct size (14.9 +/- 3.6 % vs. control 34.5 +/- 4.9%, P < 0.01) and this effect of postconditioning was abolished in the presence of isatin (100 microM), a non-specific blocker of particulate guanylyl cyclases (35.1 +/- 6%, P < 0.05 vs. postconditioning). In conclusion, pharmacological activation of pGC by BNP can effectively induce protection against reperfusion injury, by mechanisms involving K(ATP) channel opening and endogenous NO synthase activation. Furthermore, endogenous activation of pGC could play a role in the mechanism of postconditioning.
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PMID:B-type natriuretic peptide at early reperfusion limits infarct size in the rat isolated heart. 1789 17

C-type natriuretic peptide (CNP) has a demonstrated hyperpolarizing effect on vascular smooth muscle cells. However, its autocrine function, including its electrophysiological effect on endothelial cells, is not known. Here, we report the effect of CNP on the membrane potential (E(m)) of pulmonary microvascular endothelial cells and describe its target receptors, second messengers, and ion channels. We measured changes in E(m) using fluorescence imaging and perforated patch-clamping techniques. In imaging experiments, samples were preincubated in the potentiometric dye DiBAC(4)(3), and subsequently exposed to CNP in the presence of selective inhibitors of ion channels or second messengers. CNP exposure induced a dose-dependent decrease in fluorescence, indicating that CNP induces endothelial cell hyperpolarization. CNP-induced hyperpolarization was inhibited by the K(+) channel blockers, tetraethylammonium or iberiotoxin, the nonspecific cation channel blocker, La(3+), or by depletion or repletion of extracellular Ca(2+) or K(+), respectively. CNP-induced hyperpolarization was also blocked by pharmacological inhibition of PKG or by small interfering RNA (siRNA)-mediated knockdown of natriuretic peptide receptor-B (NPR-B). CNP-induced hyperpolarization was mimicked by the PKG agonist, 8-bromo-cGMP, and attenuated by both the endothelial nitric oxide synthase (eNOS) inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME), and the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Presence of iberiotoxin-sensitive, CNP-induced outward current was confirmed by perforated patch-clamping experiments. We conclude that CNP hyperpolarizes pulmonary microvascular endothelial cells by activating large-conductance calcium-activated potassium channels mediated by the activation of NPR-B, PKG, eNOS, and sGC.
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PMID:Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization. 1903 74

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