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R N Re

Publications and source records attributed to R N Re.

At least 37 records · Page 2Linked to original sources
PubMed1993

Endothelin modulates angiotensin II-induced mitogenesis of human mesangial cells.

Angiotensin II (ANG II) elicits either a hypertrophic or hyperplastic response depending on culture conditions. Human mesangial cell (HMC)-generated endothelin (ET) plays a role in mediating the hyperplastic effects of arginine vasopressin. The interaction between ANG II and ET is not described in HMC. The present study evaluates the possible effect of ANG II on HMC production of ET, its relationship to mitogenesis, and the effect of insulin. ANG II (10(-8) M) increased [3H]thymidine incorporation in proliferative HMC at 48 h (13 +/- 1 vs. 24 +/- 1 x 10(3) counts.min-1.well-1, for control vs. ANG II; P < 0.05). Cell counts showed parallel increases [12 +/- 1 (control) vs. 18 +/- 1 x 10(3) counts/well; P < 0.05]. This mitogenic effect was attenuated by a monoclonal antibody to ET-1 or the ANG II-receptor antagonist, DuP 753. Insulin potentiated the mitogenic response of ANG II through increases in HMC ET production (69 +/- 7 vs. 189 +/- 13 pg/ml, for insulin alone vs. insulin+ANG II; P < 0.05). This study supports the concept that ANG II may act as a mitogen under certain culture conditions and its effect is, in part, mediated through ET.

Angiotensin II↗
PubMed1993

Myocardial hypertrophy, angiotensin, and ACE inhibitors.

The renin-angiotensin system has long been known as a potent determinant of cardiovascular homeostasis and a powerful regulator of vascular hemodynamics. Over the last twenty years, it has become clear that components of the renin-angiotensin system are present in and, in many instances, synthesized in local tissues. The role of some of these local renin systems is now becoming clear, but the role, if any, of local production of angiotensin II in the heart and vasculature remains unknown. Recent evidence indicates that angiotensin II can serve as a growth factor for a variety of cell types including those in the cardiovascular system, and it thus appears possible that systemically or locally produced angiotensin II could subserve important functions in the determination of heart and vasculature structure. Clinical studies tend to corroborate this possibility. The potent effects of converting enzyme inhibition on the regression of left ventricular hypertrophy, the demonstration that the administration of these agents following myocardial infarction reduces detrimental cardiac remodeling, and the finding that converting enzyme inhibition prolongs survival in congestive heart failure patients all point to an important role of angiotensin II on cardiovascular function and raise the distinct possibility that angiotensin II growth effects are involved in these beneficial responses. Additionally, recent data demonstrate conclusively that under certain circumstances and in certain cell types locally produced angiotensin II can serve as an autocrine growth regulatory factor, further adding support to the idea that local renin systems may play an important role in the determination of cardiovascular structure.

Angiotensin II↗
PubMed1992

Development of innovative therapies in the large multispecialty clinic setting.

Innovation is intrinsic to medicine and to medical progress. As American medicine enters the twenty-first century, it is confronted with enormous opportunities to innovate both in the science and practice of medicine. Indeed, medicine is challenged to do so by society. Cellular and molecular medicine, along with new insights derived from health care research, offer the opportunity to improve the health of the American people without unduly taxing the economy. Research and innovation in these areas are within the grasp of many clinics, and it would seem important that, because they are major providers of health care, as many clinics as possible aggressively enter these fields in preparation for delivering health care in the next century.

Academic Medical Centers↗
PubMed1992

The use of antisense oligonucleotides to establish autocrine angiotensin growth effects in human neuroblastoma and mesangial cells.

Local renin-angiotensin systems (RAS) exist in many cell types, and angiotensin II (AII) has growth regulatory effects in some tissues. We demonstrated the presence of angiotensinogen (ANG) mRNA in cultured human mesangial cells (MC) and SHSY-5Y human neuroblastoma cells using reverse transcription and the polymerase chain reaction (RT/PCR) followed by hybridization to a human ANG-specific oligonucleotide probe. We speculated, therefore, that AII might act in an autocrine or paracrine fashion to regulate the growth of mesangial cells and neuroblastoma cells. Sense and antisense oligonucleotides were next synthesized complementary to the ANG transcription start site. Antisense but not sense oligonucleotides decreased [3H]thymidine incorporation into DNA by both MC and neuroblastoma cells. Growth of antisense oligonucleotide-treated cells was restored to control levels by the addition of AII but not by the addition of basic fibroblast growth factor. Neither oligonucleotide affected [3H]thymidine incorporation in mouse L929 cells. These data indicate that locally produced AII can act in an autocrine or paracrine fashion to alter the growth of human mesangial and neuroblastoma cells. Therefore, they suggest a role for local RAS in the pathogenesis of growth abnormalities in the cardiovascular system as well as in some forms of malignancy.

Angiotensin II↗
PubMed1991

Effects of ionic strength on endogenous nuclease activity in chelated and nonchelated chromatin.

Calf thymus chromatin, isolated using a standard (low ionic strength, but nonchelating) isolation protocol, dialyzed against either Tris-PMSF or Tris-EDTA, was reconstituted in a high salt compacting buffer (COM) or a low salt dispersing buffer (DIS) prior to digestion with endogenous nucleases. A greater level of enzyme activity occurred when chromatin was in a condensed state (COM buffer) and not chelated prior to digestion. In contrast, chromatin chelated by dialysis against Tris-EDTA prior to digestion showed higher levels of enzyme activity in the dispersed state (DIS buffer). Nonchelated undigested chromatin contained 0.280 +/- 0.16 ug copper/mg DNA and and 0.305 +/+- 0.09 ug zinc/mg DNA. Chelation removed about 78% of copper per mg DNA and approximately 65% of zinc per mg DNA. In COM buffer after a 20 min digestion, the solubilized fraction was enriched in copper showing about 20 X more metal per mg DNA than nonchelated chromatin. Approximately the same amount of zinc was found in both chelated and nonchelated chromatin while there was less zinc in chelated chromatin solubilized in DIS buffer. Thus, chelation has important effects on the digestibility of chromatin and on the type of ionic environment that provides the most favorable conditions for endogenous nuclease activity.

Animals↗
PubMed1991

Growth factors and cardiovascular structure. Implications for calcium antagonist therapy.

Abnormalities of cellular growth regulation are integral to the development of cardiovascular disorders such as atherogenesis, ventricular hypertrophy, and diabetic glomerulopathy. Moreover, cellular growth is in large measure controlled by peptide and nonpeptide growth factors that mediate their actions, in part, through the transcriptional regulation of normal cellular genes called protooncogenes. Because angiotensin II is one such growth regulatory factor and because changes in intracellular calcium are intimately involved in the action of angiotensin and other growth factors, it is likely that inhibitors of angiotensin action and calcium-channel-blocking agents will be found to have useful growth regulatory properties.

Animals↗
PubMed1991

Angiotensin-converting enzyme inhibition reduces neuroblastoma cell growth rate.

Because of the known capacity of angiotensin II to serve as a growth factor in multiple tissues, we elected to study the effects of renin-angiotensin system inhibition on the growth of human SH-SY5Y neuroblastoma cells. Cells were treated with captopril (0.05-5 mg/ml), enalapril, or enalaprilat (0.02-5 mg/ml) or saralasin (0.1-0.25 mg/ml). In all cases, statistically significant reductions in cell growth were seen over 5 days of culture. In additional experiments, captopril and enalaprilat significantly decreased thymidine incorporation into DNA in these cells. The administration of angiotensin II in the presence of captopril partially offset these suppressive effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

How to use continuous quality improvement theory and statistical quality control tools in a multispecialty clinic.

The management philosophy of continuous quality improvement (CQI) and the tools of statistical quality control (SQC) have the potential for advancing quality management in medicine as they have in industry. The authors report their favorable experience with the approach and explain how to adapt CQI principles and SQC charts and graphs, citing examples from their participation in a quality improvement effort in a multispecialty clinic serving a large hospital. The coupling of statistical techniques with modern approaches to outcome analysis may provide powerful tools not only for quality assurance and assessment but also for technology evaluation and resource allocation.

Data Collection↗
PubMed1989

The cellular biology of angiotensin: paracrine, autocrine and intracrine actions in cardiovascular tissues.

A growing body of evidence suggests that angiotensin II, the effector protein of the renin-angiotensin system, is intimately involved with cell growth in target tissues. Most recently, evidence has been provided to indicate that angiotensin II is capable of inducing a hypertrophic response in cultured arterial smooth muscle cells. At the same time, considerable evidence has been developed to indicate that local analogs of the systemic renin-angiotensin system exist in multiple tissues and, in particular, in the vascular wall and the heart. Finally, data have accumulated to indicate that local growth regulatory factors, in many instances operating through regulation of proto-oncogene transcription, are involved in the hypertrophic and hyperplastic sequelae of hypertension. Included amongst these growth factors is angiotensin II. Thus, accumulating data indicate that angiotensin II is a growth factor with potential implications for the development of the sequelae of hypertension. In addition, studies from this laboratory and others suggest that angiotensin acts at least partially through what we have called an "intracrine" mechanism to produce its effects. In these multiple actions, angiotensin may provide a paradigm for other peptide growth factors and hormones.

Angiotensin II↗
PubMed1988

Emerging issues in the cellular biology of the cardiovascular system.

Current theory suggests that life began in a prebiologic era, progressed to a ribonucleic-deoxyribonucleic cellular era, and finally entered an era characterized by multicellular organisms. If this progression is correct, it is not surprising that, as medicine studies living organisms with increasing sophistication, factors that are initially discovered to have systemic effects are, in many instances, later determined to have paracrine, autocrine or even intracellular ("intracrine") effects. This schema is potentially of value in analyzing the pathogenesis of cardiovascular disease and, in particular, the development of the sequelae of hypertension. A case is made for the idea that the actions of common peptide and nonpeptide factors at local tissue levels can play an important role in the development of atherosclerosis and left ventricular hypertrophy. In making this case, the potential roles of insulin, angiotensin II and other vasoactive factors are considered. In addition, it is argued that some peptide and nonpeptide factors with cardiovascular impact may operate in the intracellular environment, thus broadening prospects for study and intervention. Finally, genomic alterations either spontaneously occurring or resulting from chronic stimulation or viral infection are considered and their potential role is discussed.

Angiotensin II↗
PubMed1988

Does the renin-angiotensin-aldosterone system modify cardiac structure and function in essential hypertension?

To determine the impact of the renin-angiotensin-aldosterone system on left ventricular function and structure, 36 untreated patients with essential hypertension (WHO class I and II) were examined. Posterior wall thickness, relative wall thickness, and left ventricular mass were determined by M-mode echocardiography. Plasma renin activity, aldosterone, angiotensin I, and angiotensin II levels were measured by radioimmunoassay. Plasma renin activity was related to 24-hour urinary sodium excretion. Of all the endocrine parameters, only the angiotensin II level correlated with posterior wall thickness (r = 0.50, p less than 0.05) and relative wall thickness (r = 0.46, p less than 0.05). This relationship was confirmed by stepwise multiple regression analysis taking arterial pressure, obesity, and sodium excretion into account (p less than 0.05). Plasma renin activity but not the angiotensin II level correlated positively with the ejection fraction (r = 0.42, p less than 0.05) and velocity of circumferential fiber shortening (r = 0.57, p less than 0.01). Thus, angiotensin II emerged as a determinant of left ventricular structural adaptation in essential hypertension.

Aldosterone↗
PubMed1987

Cellular mechanisms of growth in cardiovascular tissue.

Left ventricular hypertrophy is a complex cellular response to a variety of pathologic states. In recent years it has become clear that a variety of hormones are present in the heart and may participate in the genesis of left ventricular hypertrophy. Our group has demonstrated the synthesis of renin by cultured canine arterial smooth muscle cells and has recently demonstrated the presence of renin and angiotensin II in myocardial cell preparations. Angiotensin II concentration was (+/- standard error of the mean) 4.19 +/- 1.52 pg/10(6) cells. Evidence has been developed to suggest that these components of the renin-angiotensin system are modulatable. These data, taken together with studies from our laboratory and others, raise the distinct possibility that components of the renin-angiotensin system together with catecholamines play a role in the genesis of left ventricular hypertrophy. Recent evidence suggests that the myc proto-oncogene is activated in cells undergoing catecholamine-induced hypertrophy and our laboratory has detected activation of the sis proto-oncogene in at least 1 model of left ventricular hypertrophy. These findings raise the possibility that similar pathogenetic cellular mechanisms operate to produce myocardial hypertrophy, vascular hyperplasia and hypertrophy, and some forms of benign neoplasia. The possible significance of these findings and their relation to peptide hormones and growth factors are discussed.

Animals↗
PubMed1987

The renin-angiotensin systems.

The renin-angiotensin systems are important regulators of cardiovascular homeostasis and participate in a variety of pathological conditions. Recent advances have not only clarified the functioning of the systemic renin cascade but have also indicated the importance of the generation of angiotensin in tissues.

Homeostasis↗
PubMed1987

Evidence for the existence of renin in the heart.

Renin and other components of the renin-angiotensin system have been reported to be present in many extrarenal tissues. We have detected reninlike activities in mouse and rat hearts. Cardiac renin has a pH optimum similar to that of renal renin and its activity is inhibited by antirenin antibody. This enzyme is synthesized in the heart, based on the following evidence: renin messenger RNA was detected in mouse heart by Northern blot hybridization and renin activity was found in isolated cardiac myocytes. Nifedipine lowered the intracellular renin activity of isolated cardiac myocytes in vitro. These results demonstrate the existence of a cardiac renin system that may play a local regulatory role on cardiac function.

Animals↗
PubMed1985

Recognition of peptide orientation: studies with angiotensin II in the guinea-pig.

Antipeptide sera of defined subspecificities were obtained when angiotensin II was unidirectionally conjugated to its carrier protein. Antisera with predominantly amino terminal specificity were produced when guinea-pigs were immunized with angiotensin II conjugated via its carboxy terminus to thyroglobulin. When angiotensin II was coupled via its amino terminus, carboxy terminal-specific antisera were obtained. The same conjugates failed to provide antisera with the corresponding specificities when rabbits were used instead of guinea-pigs. This work demonstrates that the peptide-protein coupling strategy may affect the specificity of the resulting antiserum.

Angiotensin II↗