Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to examine the alterations in vascular relaxation responsiveness to endothelium-dependent or -independent vasodilators, including atrial natriuretic peptide (ANP) and acetylcholine, in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits during the progression of the atherosclerotic plaque. WHHL rabbits were divided into two groups according to age: group 1, 6-11 months, and group 2, 12-18 months. The isolated thoracic aortas obtained from both normal (control) and WHHL rabbits were suspended in a bath containing oxygenated Krebs' buffer for recording of isometric force. The endothelium-dependent relaxation evoked by acetylcholine was reduced in group 1 WHHL rabbits and decreased progressively in proportion to the degree of atherosclerosis progression when compared with age-matched control rabbits. ANP-induced relaxation was not significantly decreased in group 1 WHHL rabbits. However, ANP-induced relaxation was markedly impaired in group 2 WHHL rabbits. Thoracic aortas with severe atherosclerosis were less sensitive to ANP, with a significant increase in the median effective dose, although maximum relaxation induced by ANP was not reduced. Accumulation of cyclic GMP induced by ANP and acetylcholine was markedly reduced in atherosclerotic arteries obtained from group 2 WHHL rabbits compared with control rabbits. Vascular relaxation elicited by nitroglycerin or isoproterenol was not significantly impaired in atherosclerotic arteries from either group 1 or group 2 WHHL rabbits. From these results, we suggest that ANP-induced cyclic GMP formation and vascular relaxation via particulate guanylate cyclase in vascular smooth muscle cells are impaired in severely atherosclerotic arteries.
 ...
PMID:Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression. 131 25

A diet containing 0.3% cholesterol was given to male New Zealand rabbits for 16 weeks; this produced atherosclerotic lesions (fatty streaks) on 80% of the intimal surface of the thoracic aorta and on 45% of the intimal surface of the abdominal aorta. The endothelium-dependent relaxations induced by acetylcholine, substance P and ionophore A23187 were inhibited in the atherosclerotic aortas. Besides the endothelium-independent relaxations induced by nitroglycerine, the relaxations induced by atrial natriuretic peptide (ANF) were also significantly reduced in the more atherosclerotic thoracic aorta. In bioassay experiments it was found that acetylcholine and substance P caused a smaller release of endothelium-derived relaxing factor (EDRF) from atherosclerotic thoracic aortas than from control thoracic aortas: the EDRF released by the vasodilators evoked less relaxation in atherosclerotic detector abdominal aortas than in control detector abdominal aortas. Nitric oxide evoked significantly less transient relaxation in the atherosclerotic thoracic and abdominal aortas than in the respective control tissues. The data indicate that as experimental atherosclerosis in the rabbit progresses, both vascular activity and EDRF release become affected; this leads to a complete loss of endothelium-dependent relaxation in the more atherosclerotic blood vessels.
 ...
PMID:Release and vascular activity of endothelium-derived relaxing factor in atherosclerotic rabbit aorta. 170 15

In cultured rabbit aortic smooth muscle cells (SMCs), sodium nitroprusside (SNP) (10(-7) to 10(-4) M), atrial natriuretic peptide (ANP) (10(-9) to 10(-6) M) and 8-bromo-cyclic GMP (10(-6) to 10(-3) M) inhibited the whole blood serum (WBS)-induced DNA synthesis by about 30%. The doses of SNP and ANP necessary for the inhibition of the WBS-induced DNA synthesis were similar to those necessary for the formation of cellular cyclic GMP (cGMP). These agents were effective even when added 6 h after stimulation of the cells with WBS. These results suggest that cGMP inhibits the proliferation of rabbit aortic SMCs by inhibiting the progression from the G1 into S phase of the cell cycle and raise the possibility that cGMP-elevating vasodilators may suppress the atherogenic process by inhibiting vascular SMC proliferation.
Atherosclerosis 1989 Dec
PMID:Antiproliferative action of cyclic GMP-elevating vasodilators in cultured rabbit aortic smooth muscle cells. 255 61

Cirrhosis is associated with several circulatory abnormalities. A hyperkinetic circulation characterized by increased cardiac output and decreased arterial pressure and peripheral resistance is typical. Despite this hyperkinetic circulation, some patients with alcoholic cirrhosis have subclinical cardiomyopathy with evidence of abnormal ventricular function unmasked by physiologic or pharmacologic stress. Florid congestive alcoholic cardiomyopathy develops in a small percentage, but the concurrent presence of cirrhosis seems to retard the occurrence of overt heart failure. Even nonalcoholic cirrhosis may be associated with latent cardiomyopathy, although overt heart failure is not observed. Tense ascites is associated with some cardiac compromise, and removing or mobilizing ascitic fluid by paracentesis or peritoneovenous shunting results in short-term increases in cardiac output. Cirrhosis also appears to be associated with a decreased risk of major coronary atherosclerosis and an increased risk of bacterial endocarditis. Small hemodynamically insignificant pericardial effusions may be seen in ascitic patients. The release of atrial natriuretic peptide appears to be unimpaired in cirrhosis, although the kidney may be hyporesponsive to its natriuretic effects.
 ...
PMID:Cardiac abnormalities in liver cirrhosis. 269 Apr 63

The effect of endothelin-1 (ET-1) on proliferation of aortic vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive (SHRs) and normotensive Wistar-Kyoto (WKY) rats was assessed by the measurement of [3H]-thymidine incorporation into DNA. ET-1 stimulated DNA synthesis in a concentration-dependent manner. Half-maximal stimulation occurred at a concentration of 7 x 10(-11) M. Three separate administrations of ET-1 to the cell cultures resulted in a half-maximal stimulation at 3 x 10(-12) M in of VSCMs from SHRs. VSMCs from SHRs responded to a far greater extent compared with WKY rats. The stimulatory effect of ET-1 was significantly attenuated by atrial natriuretic peptide (ANP). Repeated administration of ANP led to exacerbation of the inhibitory effect. Serum-stimulated DNA synthesis was not influenced by ANP. The proliferative action of ET-1 and the inhibition by ANP are discussed with respect to the development of vascular disease in atherosclerosis and hypertension.
 ...
PMID:Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth-muscle cells. 750 59

Vascular endothelial cell migration is proposed to be an important process in the initiation and progression of atherosclerosis. We designed the present study to examine the effects of atrial and brain natriuretic peptides on fetal calf serum-stimulated migration of cultured rat aortic endothelial cells using Boyden's chamber method. Fetal calf serum clearly stimulated migration in a concentration- and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain natriuretic peptide-45, which are the major circulating forms of atrial and brain natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP, significantly inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide-(5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat brain natriuretic peptide-45 with respect to inhibiting migration and increasing cGMP levels. These results indicate that atrial and brain natriuretic peptides inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably through a cGMP-dependent process.
 ...
PMID:Inhibition by cardiac natriuretic peptides of rat vascular endothelial cell migration. 764 73

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells (ECs) and acts as an endothelium-derived relaxing peptide. We further demonstrated the detection of the gene transcripts of CNP and atrial natriuretic peptide (ANP) B receptor, a specific receptor for CNP, in human blood vessels. We thus propose the existence of a vascular natriuretic peptide system (NPS). CNP secretion was also demonstrated to be stimulated by various growth factors and cytokines. To clarify the significance of vascular NPS in proliferative vascular complications associated with diabetes, hypertension, or atherosclerosis, in the present study we examined the effect of insulin on CNP secretion from cultured ECs. Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC. IGF-I had no significant effect on CNP secretion. Insulin, therefore, can be a potent inhibitor of CNP secretion through the activation of insulin receptor. Since CNP has been shown to be a potent inhibitor of vascular smooth muscle cell proliferation, the present study suggests the possibility that attenuated activity of vascular NPS is associated with hyperinsulinemia, which might result in proliferative vascular lesions.
 ...
PMID:Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide. 867 95

Growth arrest-specific homeobox (Gax) gene was isolated from rat aorta cDNA library and its expression was largely confined to the cardiovascular tissues. Gax gene was rapidly downregulated by platelet-derived growth factor in vascular smooth muscle cells (VSMCs) and overexpressed Gax was reported to reduce the neointimal thickening after balloon injury in vivo. We have demonstrated that angiotensin II (Ang II) stimulates vascular growth. In contrast, we also reported that C-type natriuretic peptide (CNP) is secreted from vascular endothelial cells to act as a novel endothelium-derived relaxing peptide and inhibits vascular growth via cGMP cascade. In the present study, we examined the effects of Ang II and CNP on Gax gene expression in VSMCs. In quiescent rat aortic VSMCs. Gax mRNA (2 3 kb) level became negligible 6 hours after the addition of Ang II (10(-6) mol/L). The inhibitory action of Ang II on Gax mRNA expression (ED50: 10(-11) mol/L) was almost completely blocked by an AT1R antagonist, CV11974. In contrast, CNP 10(-6) mol/L augmented Gax mRNA expression to exhibit 1.8-fold increase of the control 12 hours after the stimulation. This effect of CNP was mimicked by the addition of 8-bromoadenosine 3'-5'-cyclic monophosphate. The addition of C-ANF[4-23], an atrial natriuretic peptide-C receptor-specific agonist and devoid of stimulating cGMP production, exhibited no effect on Gax mRNA expression. Simultaneous administration of Ang II and CNP revealed that CNP (10(-6) mol/L) significantly attenuated the inhibitory action of Ang II (10(-10) mol/L) on Gax mRNA expression. These results suggest that Gax is a common transcription factor involved in the signaling pathway of vascular growth for Ang II and CNP and regulates the cell cycle and/or phenotype of VSMCs for vascular remodeling in hypertension and atherosclerosis.
 ...
PMID:Opposite regulation of Gax homeobox expression by angiotensin II and C-type natriuretic peptide. 903 31

Mammalian cell-surface peptidases participate in the postsecretory processing and metabolism of neuropeptides and peptide hormones. Neutral endopeptidase-24.11 (NEP) is the prototype of a family of zinc metallopeptidases that also includes the endothelin-converting enzymes (ECE) and which are structurally related to the bacterial enzymes thermolysin and lactococcal endopeptidase. Two other mammalian gene products exhibit strong homology with NEP: the erythrocyte cell-surface antigen, KELL; and the putative product of the PEX gene, which has been associated with X-linked hypophosphatemic rickets. No enzymic activity has yet been attributed to KELL and PEX proteins, and they remain peptidases in search of a substrate. A wide range of biologically active peptide substrates has been described for NEP, of which the enkephalins and the atrial natriuretic peptide family have assumed greatest significance. Endothelin-converting enzyme catalyses the final step in the biosynthesis of the vasoconstrictor peptide, endothelin (ET). Like NEP, it is a type II integral membrane protein, but is expressed predominantly in endothelial cells. Isoforms of ECE (ECE-1alpha, ECE-1beta, and ECE-2) exist that differ in a number of characteristics. In particular, ECE-1, through the paracrine effects of ET-1, may contribute to the proliferation of smooth muscle after angioplasty and to the development of human atherosclerosis. Inhibitors of ECE and NEP may have important therapeutic applications in cardiovascular and renal medicine.
 ...
PMID:Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. 914 2

Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.
 ...
PMID:[Natriuretic peptide system]. 928 3


1 2 3 4 Next >>