Routine measurement of natriuretic peptide to guide the diagnosis and management of chronic heart failure.
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Biomarkers↗
Biomedical subjects
Toshio Nishikimi
Publications and source records attributed to Toshio Nishikimi.
Association of plasma atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, and brain natriuretic peptide levels with coronary artery stenosis in patients with normal left ventricular systolic function.
PURPOSE: To examine whether coronary artery stenosis affects plasma levels of atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (proANP), and brain natriuretic peptide (BNP) in patients with normal left ventricular systolic function. METHODS: We studied 104 consecutive patients with normal left ventricular function and suspected coronary artery stenosis. Plasma natriuretic peptide levels were measured by immunoradiometric assays. RESULTS: Plasma levels of ANP, N-terminal proANP, and BNP were higher in patients with (n = 65) than in those without (n = 39) coronary artery stenosis, whereas hemodynamic variables were similar. Patients who had coronary artery stenosis with only distal lesions (n = 36) had higher levels of all three natriuretic peptides than did patients with no coronary artery stenosis. N-terminal proANP levels were significantly higher in patients who had coronary artery stenosis with proximal lesions (n = 29) than in patients who had coronary artery stenosis with only distal lesions and those with no coronary artery stenosis. Multiple logistic regression analysis revealed that N-terminal proANP, but not ANP or BNP, was independently associated with coronary artery stenosis after adjusting for clinical and demographic variables (odds ratio per 100 fmol/mL increase = 1.9; 95% confidence interval: 1.9 to 2.6; P = 0.01). However, the sensitivity, specificity, and positive and negative predictive values of each peptide were not sufficiently high to be used for prediction. CONCLUSION: N-terminal proANP may be associated with clinically important coronary artery stenosis in patients with normal left ventricular systolic function, but its clinical usefulness may be limited.
Atrial Natriuretic Factor↗
Different secretion patterns of two molecular forms of cardiac adrenomedullin in pressure- and volume-overloaded human heart failure.
BACKGROUND: In the final step of production of adrenomedullin (AM), an inactive intermediate form of glycine-extended AM (AM-glycine) is converted to the active mature form of adrenomedullin (AM-mature) by enzymatic amidation. Recent studies have revealed that AM-mature and AM-glycine circulate in human plasma. In this study, we investigated the differences of the concentrations of cardiac AM between pressure-overloaded (PO) heart failure (HF) and volume-overloaded (VO)-HF in humans. METHODS AND RESULTS: We measured AM-mature and AM-glycine by immunoradiometric assays in pericardial fluid and plasma in 38 patients who underwent valve replacement surgery (PO-HF: aortic stenosis, n=14; VO-HF: aortic or mitral regurgitation, n=24). Stable coronary artery disease with normal left ventricular function served as the control (n=24). Plasma AM-mature (VO-HF: +59%, PO-HF: +65%, P<.05) and AM-glycine (VO-HF: +43%, PO-HF: +50%, P<0.05) were similarly higher in the 2 HF groups than in the control group. Interestingly, pericardial fluid AM-mature was markedly higher than that in plasma (control: +789%, VO-HF: +1050%, PO-HF: +1745%, all P<.001). Pericardial fluid AM-mature was higher in VO-HF (+106%, P<.01) than in controls and they were further increased in PO-HF (+243%, P<.05). Pericardial fluid molecular forms of AM correlated with left ventricular systolic pressure, but not with left ventricular end-diastolic volume index in PO-HF. In contrast, they correlated with left ventricular end-diastolic volume index, but not with left ventricular systolic pressure in VO-HF. CONCLUSION: These results suggest that cardiac AM is differently regulated from plasma AM and that cardiac AM production is upregulated in both types of HF in response to each different stimulus.
Adrenomedullin↗
Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats.
OBJECTIVE: The present study was designed to clarify whether the Rho-Rho-kinase pathway is involved in the process of hypertensive glomerulosclerosis and to assess the therapeutic effect of fasudil, a specific Rho-kinase inhibitor. METHOD AND RESULTS: Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) were fed a high-salt diet at 6 weeks of age. Fasudil (30 mg/kg per day) was administered for 7 weeks to DS starting at the age of 11 weeks. After 7 weeks, untreated DS were characterized by decreased kidney function, increased proteinuria, abnormal morphological findings, increased adrenomedullin and atrial natriuretic peptide (ANP) levels, and increased renal messenger RNA expression of RhoB, Rho-kinasealpha, Rho-kinasebeta, collagen I and collagen III, and transforming growth factor-beta (TGF-beta) in the renal cortex compared with DR. Chronic fasudil treatment significantly improved renal function (serum creatinine, -26%; blood urea nitrogen, -41%; creatinine clearance, +42%), proteinuria (-24%) and histological findings (glomerular injury score, -49%; afferent arteriolar injury score, -17%) without changing blood pressure compared with untreated DS. Interestingly, long-term fasudil treatment decreased the plasma adrenomedullin (-25%) and ANP (-49%), but did not change the plasma renin or aldosterone. Furthermore, fasudil significantly decreased the messenger RNA expression of TGF-beta (-20%), collagen I (-23%), and collagen III (-24%) in the renal cortex. However, there were still significant differences in the aforementioned parameters between DR and fasudil-treated DS. CONCLUSION: These results suggest that the Rho-Rho-kinase pathway may be partly responsible for the pathogenesis of hypertensive glomerulosclerosis independently of blood pressure in DS, and that chronic inhibition of the Rho-Rho-kinase pathway may be a new strategy for treating hypertensive nephrosclerosis.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
[Adrenomedullin in essential hypertension].
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Adrenomedullin↗
[Urotensin II and cardiac disease].
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Amino Acid Sequence↗
Chronic administration of adrenomedullin attenuates transition from left ventricular hypertrophy to heart failure in rats.
Acute administration of adrenomedullin (AM) exerts beneficial hemodynamic, renal, and neurohormonal effects in heart failure (HF). However, chronic effects of AM administration on HF remain unknown. This study sought to examine the effect of chronic infusion of AM on progression of HF in rat. Human recombinant AM was administered by osmotic minipump for 7 weeks in the HF model of Dahl salt-sensitive rats. The effect was compared with vehicle and diuretic treatment group. Chronic AM infusion significantly decreased left ventricular end-diastolic pressure, right ventricular systolic pressure, right atrial pressure, and left ventricular weight/body weight (P<0.01 for all). AM significantly attenuated the increase in circulating renin-aldosterone, endogenous rat AM, and atrial natriuretic peptide levels (P<0.01 for all). AM also inhibited the myocardial tissue levels of angiotensin II and atrial and brain natriuretic peptide (P<0.01 for all). These changes were associated with the improvement of cardiac output and systemic vascular resistance (both P<0.05). Furthermore, AM improved left ventricular end-systolic elastance (P<0.01). These improvements were greater in the AM than in the diuretic group, although both drugs similarly decreased systolic blood pressure and increased urinary sodium excretion. Kaplan-Meier survival analysis showed that AM significantly prolonged survival time compared with diuretic (P<0.05) and vehicle (P<0.01) treatment groups. These results suggest that endogenous AM plays a compensatory role in HF and that chronic AM infusion attenuates progression of left ventricular dysfunction and improves survival, at least in part, through inhibition of circulating and myocardial neurohormonal activation.
Adrenomedullin↗
Increased atherosclerosis and smooth muscle cell hypertrophy in natriuretic peptide receptor A-/-apolipoprotein E-/- mice.
OBJECTIVE: Natriuretic peptide signaling is important in the regulation of blood pressure as well as in the growth of multiple cell types. To examine the role of natriuretic peptide signaling in atherosclerosis, we crossbred mice that lack natriuretic peptide receptor A (NPRA; Npr1-/-) with atherosclerosis-prone mice that lack apolipoprotein E (apoE; Apoe-/-). METHODS AND RESULTS: Doubly deficient Npr1-/-Apoe-/- mice have increased blood pressure relative to Npr1+/+Apoe-/- mice (118+/-4 mm Hg compared with 108+/-2 mm Hg, P<0.05) that is coincident with a 64% greater atherosclerotic lesion size (P<0.005) and more advanced plaque morphology. Additionally, aortic medial thickness is increased by 52% in Npr1-/-Apoe-/- mice relative to Npr1+/+Apoe-/- mice (P<0.0001). Npr1-/-Apoe-/- mice also have significantly greater cardiac mass (9.0+/-0.3 mg/g body weight) than either Npr1+/+Apoe-/- mice (5.8+/-0.2 mg/g) or Npr1-/-Apoe+/+ mice (7.1+/-0.2 mg/g), suggesting that the lack of both NPRA and apoE synergistically enhances cardiac hypertrophy. CONCLUSIONS: These data provide evidence that NPR1 is an atherosclerosis susceptibility locus and represents a potential link between atherosclerosis and cardiac hypertrophy. Our results also suggest roles for Npr1 as well as Apoe in regulation of hypertrophic cell growth.
Animals↗
Altered gene expression of adrenomedullin and its receptor system and molecular forms of tissue adrenomedullin in left ventricular hypertrophy induced by malignant hypertension.
To investigate the pathophysiological role of adrenomedullin (AM) in left ventricular hypertrophy (LVH) in hypertension, we measured the plasma level, left ventricle (LV) tissue level, and mRNA abundance of AM and the mRNA abundance of the AM receptor system in the LV. We also analyzed the molecular forms of AM in the plasma and LV tissue and investigated the relationships between AM and the degree of LVH. We studied the following three groups: control Wistar Kyoto rats (WKY), control spontaneously hypertensive rats (SHR), and deoxycorticosterone acetate (DOCA)-salt SHR (D-SHR). We measured AM-mature, active form, and AM-total (active form+inactive form) in plasma and the LV by a newly developed immunoradiometric assay. Gene expression of AM was measured by Northern blot analysis and gene expression of AM receptor system components, such as calcitonin receptor-like receptor (CRLR), receptor activity modifying protein 2 (RAMP2), and RAMP3 was measured by the reverse transcription polymerase chain reaction method. After 3 weeks of DOCA treatment, D-SHR was characterized by higher blood pressure, LV weight, and plasma atrial natriuretic peptide levels compared with those in the other two groups. Plasma AM-mature and AM-total levels were significantly higher in D-SHR than in the other two groups, whereas there were no significant differences in the AM-mature/AM-total ratio among the three groups. On the other hand, LV tissue AM-mature and AM-total levels were also significantly higher in D-SHR than in the other two groups, and the AM-mature/AM-total ratio was significantly higher in LV tissues than in plasma. Furthermore, the LV tissue AM-mature/AM-total ratio was significantly higher in D-SHR compared with the other two groups. The LV tissue AM-mature/AM-total ratio was significantly correlated with LV weight/body weight (r=0.92, p<0.001). The gene expression levels of AM, CRLR, RAMP2, and RAMP3 in the LV were significantly higher in D-SHR than in the other two groups. These results suggest that the AM amidating enzyme activity, ligand, and receptor system are all upregulated in the LV hypertrophy in this malignant hypertensive rat model. Considering that AM serves as a local antihypertrophic autocrine and/or paracrine factor, the induction of AM system observed here may modulate the pathophysiology of LV hypertrophy in certain forms of malignant hypertension.
Adrenomedullin↗
Decreased mature adrenomedullin levels in feto-maternal tissues of pregnant women with histologic chorioamnionitis.
Adrenomedullin (AM) gains its bioactivity by amidation at its C-terminal, forming "mature AM." The mature AM and the expression of AM receptor component mRNAs, receptor activity-modifying protein 2 and calcitonin receptor-like receptor, from feto-maternal tissues of normal pregnant women and women with histologic chorioamnionitis were examined to clarify the pathophysiological features of this intrauterine infection. Samples of the placenta and fetal membranes were obtained from 10 normal pregnant women and eight women with histologic chorioamnionitis under informed consent. Mature AM in the fetal membranes was significantly lower in patients with chorioamnionitis than in normal pregnant women. On the other hand, there were no differences in mature AM levels in the placenta between the two groups. The total AM levels as a sum of mature and immature AM were not significantly different between the two groups in either area. The ratio of mature AM/total AM was significantly decreased in the fetal membranes of the patients with chorioamnionitis compared with normal pregnancies, but not in the placenta. Also, levels of mature AM were negatively correlated with C-reactive protein concentrations. The present results thus suggested that mature AM may have some role in chorioamnionitis.
Adrenomedullin↗
Ventricular adrenomedullin system in the transition from LVH to heart failure in rats.
We investigated whether adrenomedullin (AM) participates in the pathophysiology during the transition from left ventricular hypertrophy (LVH) to heart failure (HF). We used the Dahl salt-sensitive (DS) rat model, in which systemic hypertension causes LVH at the age of 11 weeks, followed by HF at the age of 18 weeks. Two molecular forms of AM levels in the plasma and myocardium at the LVH stage were significantly elevated compared with those in controls, and they were further increased at the HF stage. Interestingly, the LV tissue AM-mature/AM-total ratio was higher only in the HF group than in controls and LVH. The LV tissue AM-mature/AM-total ratio, AM-mature, and AM-total concentrations had close relations with the LV weight/body weight (r=0.72, r=0.79, and r=0.70, respectively; all P<0.001). AM gene expression was significantly increased at the LVH stage and was further increased at the HF stage. Furthermore, gene expression of AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 2 (RAMP2), and RAMP3 were significantly increased at the stage of LVH and HF. Regarding other neurohumoral factors, plasma renin and aldosterone levels were not increased at the LVH stage but were increased at the HF stage, whereas atrial natriuretic peptide was increased in both the plasma and myocardium at the LVH stage and was further increased at the HF stage. These results suggest that induction of the cardiac AM system, including the ligand, receptor, and amidating activity, may modulate pathophysiology during the transition from LVH to HF in this model.
Adrenomedullin↗
Upregulation of ligand, receptor system, and amidating activity of adrenomedullin in left ventricular hypertrophy of severely hypertensive rats: effects of angiotensin-converting enzyme inhibitors and diuretic.
OBJECT: We investigated the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand, receptor and amidating activity in the hypertrophied heart in severe hypertension. METHOD: We studied the following four groups: control Wistar-Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor is converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly is converted to active mature AM (AM-m) by enzymatic amidation. We measured AM-m, AM-total (AM-T; AM-T = AM-m + AM-Gly), and atrial natriuretic peptide (ANP) in the plasma and left ventricle (LV) by immunoradiometric assay. We also measured gene expression of AM and ANP was and gene expression and protein levels of AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor-activity modifying protein (RAMP) 2 and RAMP3. RESULTS: At 7 weeks old, SHR-SP had higher blood pressure and ANP mRNA levels and lower plasma AM-T compared with WKY, however, there were no differences in other indices between the two groups. At 17 weeks old, SHR-SP had increased blood pressure, LV weight, plasma and LV ANP levels and mRNA levels of ANP compared with WKY. AM-m and AM-T levels in plasma (AM-m: + 31%; AM-T: + 56%) and the LV (AM-m: + 84%; AM-T: + 31%) were significantly higher in SHR-SP than in WKY. The LV tissue AM-m/AM-T ratio was significantly higher in SHR-SP (93.2%) than in WKY. The mRNA levels of AM, CRLR, and RAMP2 in the LV were significantly higher in SHR-SP than in WKY. Captopril and trichlormethiazide similarly decreased blood pressure and LV hypertrophy with the reduction of the LV AM-m and AM-T levels and mRNA abundance of AM and its receptor component. CONCLUSION: These results suggest that cardiac AM system is upregulated in the hypertrophied heart in this hypertension model. Considering that AM acts as an anti-remodeling autocrine and/or paracrine factor, upregulation of the AM system may modulate the pathophysiology in LV hypertrophy.
Adrenomedullin↗
Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts.
C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-beta1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.
Age Factors↗
Multiple left ventricular diverticula detected by second harmonic imaging: a case report.
A 51-year-old Japanese man was admitted to hospital for evaluation of anterior chest pain at rest. He had a past history of cerebellar infarction when he was 47 years old. A conventional 2-dimensional echocardiogram revealed normal left ventricular function, and no abnormal findings. However, second harmonic imaging demonstrated 2 noncontractile diverticula at the submitral annular portion of the posterior wall of the left ventricle. Second harmonic imaging revealed another contractile diverticulum at the anterior wall of left ventricle in the short-axis view. These findings were confirmed by left ventriculography. After confirming the diagnosis of multiple left ventricular diverticula, a rare type of congenital anomaly, anticoagulant therapy was started and he is well to date. Left ventricular diverticula are clinically very important because they are often associated with serious complications such as systemic thromboembolism. Enhancement of the left ventricular endocardial borders by second harmonic imaging is useful for the diagnosis of left ventricular diverticula.
Anticoagulants↗
Cardioprotective effect of adrenomedullin in heart failure.
Many neurohumoral factors participate in the pathophysiology of heart failure, and adrenomedullin (AM) may be involved in their derangement. This work reviews the accumulating evidence in support of a compensatory role of AM in heart failure, and describes the possible mechanisms of this role. It has been established that plasma AM levels are increased in patients with heart failure in proportion to the severity of the disease. Furthermore, recent studies suggest that plasma AM level is an independent prognostic indicator of heart failure. Thus, AM may be not only a biochemical marker for evaluating the severity of heart failure, but also a prognostic indicator of this syndrome. In patients with heart failure, AM production is increased not only in the plasma, but also in the heart. AM secretion from the failing human heart is also increased, but this increase is small and responds slowly to the stimulus. This phenomenon may be explained by the fact that AM is secreted via a constitutive pathway and that AM is an autocrine and/or a paracrine factor in the heart. An experiment using cultured myocytes suggested that cytokines and mechanical stress are important stimuli for AM production in the heart. Regarding the action of AM in the heart, recent studies have suggested that AM exerts an inotropic action both in vitro and in vivo. AM also attenuates cardiac hypertrophy in myocytes and inhibits proliferation and collagen production in cardiac fibroblasts. These results suggest that AM may be an antifibrotic, antihypertrophic, and positive inotropic factor in the failing and hypertrophied heart. Because AM has many cardiorenal actions, AM administration may be useful for the treatment of heart failure. Indeed, acute administration of AM has been shown to improve the hemodynamics, renal function, and hormonal parameters in patients with heart failure. Moreover, recent studies have shown that AM gene therapy or long-term AM infusion significantly improved cardiac hypertrophy and fibrosis, and prolonged the survival time in an animal model of hypertension and heart failure. In conclusion, these findings suggest that AM plays a compensatory role in the pathophysiology of heart failure and that administration of AM may be a new and promising approach for the treatment of patients with this syndrome.
Adrenomedullin↗
Pulmonary vasodilator response to adrenomedullin in patients with pulmonary hypertension.
This study sought to investigate pulmonary vasodilator responses to intrapulmonary and intravenous infusion of adrenomedullin (AM) in patients with pulmonary hypertension. In 10 patients with pulmonary hypertension, blood flow velocity in a segmental pulmonary artery was measured using a Doppler flow wire during intrapulmonary infusion of AM, acetylcholine (ACh), and adenosine triphosphate (ATP). The hemodynamic effects of intravenously administered AM (0.05 microg/kg/min) were examined in another 5 patients with primary pulmonary hypertension. Intrapulmonary infusion of AM, ACh or ATP caused a significant dose-dependent increase in blood flow velocity in a segmental pulmonary artery, respectively. The increase in flow velocity with AM at 10(-8) mol/l (41 +/- 6% of the baseline value) was comparable to that with ACh at 10(-4) mol/l (39 +/- 11%) and that with ATP at 10(-5) mol/l (36 +/- 14%), suggesting a strong pulmonary vasodilator activity of AM. Intravenous infusion of AM produced a 41% increase in cardiac index (p < 0.05) and a 30% decrease in pulmonary vascular resistance (p < 0.05) with a 3% reduction in mean pulmonary arterial pressure (p = NS). These results suggest that, on a molar basis, AM may have much more potent pulmonary vasodilator activity than ACh and ATP, and thus may have beneficial hemodynamic effects in patients with pulmonary hypertension.
Acetylcholine↗
The effect of pituitary adenylate cyclase activating polypeptide on cultured rat cardiocytes as a cardioprotective factor.
In the cardiovascular system, pituitary adenylate cyclase activating polypeptide (PACAP) exhibits not only vasodilation but also positive inotropic action by increasing cardiac output. Then the effect of PACAP in cultured cardiovascular cells was examined. In neonatal rat myocytes, PACAP evoked concentration-dependent increase in intracellular cyclic AMP content more potently than vasoactive intestinal polypeptide (VIP). However, in neonatal rat nonmyocytes, PACAP and VIP showed equal potency. The characterization of the subtype of PACAP/VIP receptors by RT-PCR analysis revealed that PAC1 receptor mRNA is dominantly present in the myocytes, but VPAC2 receptor mRNA is abundant in the nonmyocytes. In the myocytes, PACAP did not change the protein synthesis stimulated by endothelin or by itself. However, PACAP moderately stimulated the secretion of atrial natriuretic polypeptide (ANP). On the other hand, PACAP inhibited the protein synthesis and DNA synthesis of the nonmyocytes. These indicate that PACAP might be involved in the regulation of cardiac hypertrophy and fibrosis as a cardioprotective factor.
Animals↗
Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, inhibits cardiac myocyte hypertrophy induced by endothelin.
We investigated the direct effects of cerivastatin on hypertrophy of cultured rat neonatal myocytes induced by endothelin and the mechanism by which cerivastatin exerts its effects. Endothelin significantly increased [14C]phenylalanine ([14C]Phe) incorporation, atrial natriuretic peptide (ANP) release, ANP mRNA expression and cell size. Cerivastatin significantly reduced the increase in [14C]phenylalanine incorporation, ANP peptide release, ANP mRNA expression and cell size induced by endothelin, but pravastatin did not. Exogenous mevalonate completely prevented the inhibitory effect of cerivastatin on [14C]phenylalanine incorporation, ANP release and cell size. Cotreatment with geranylgeranyl pyrophosphate also attenuated the effect of cerivastatin on [14C]phenylalanine incorporation, but cotreatment with farnesyl pyrophosphate or squalene did not. Furthermore, both Rho inhibitor C3 exoenzyme and Rho-dependent kinase inhibitor, (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide.2HCl (Y27632) significantly decreased [14C]phenylalanine incorporation, ANP secretion, ANP mRNA expression and cell size. Cerivastatin decreased endothelin-induced Rho protein expression, and mevalonate and geranylgeranyl pyrophosphate reversed this effect. These results suggest that cerivastatin directly attenuates cardiac hypertrophy induced by endothelin in cultured rat myocytes partly by inhibition of the Rho pathway.
ADP Ribose Transferases↗