GENETICS OF ATRIAL NATRIURETIC FACTOR AND HYPERTENSION

心房钠尿因子和高血压的遗传学

• 批准号: 3349725
• 负责人: ROBERT M GRAHAM
• 金额: $ 38.23万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 1991-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349725
• 关键词: Bartter's syndrome; affinity chromatography; atrial natriuretic peptide; blood chemistry; blood flow measurement; body water; complementary DNA; dogs; electrolyte balance; electron microscopy; familial hypertension; genetic manipulation; genetic transcription; genetic translation; heart cell; high performance liquid chromatography; histochemistry /cytochemistry; homeostasis; human subject; hypertension; immunochemistry; immunoprecipitation; laboratory mouse; laboratory rabbit; laboratory rat; linkage mapping; molecular cloning; molecular genetics; monoclonal antibody; nucleic acid probes; peptide chemical synthesis; peptide structure; protein biosynthesis; radioimmunoassay; radiotracer; renal hypertension; saluretic; synthetic peptide; tissue /cell culture

Atrial natriuretic factor (ANF) is a recently discovered peptide stored in specific granules within the atrial myocyte that has potent natriuretic and vasorelaxant properties. Although considerable progress has been made in elucidating its primary structure and in isolating and characterizing its gene, the significance of ANF as a humoral factor in maintaining cardiovascular homeostasis, particularly in relation to volume and blood pressure control, is virtually unknown. It is the major aim of this proposal to define this role. The approach is multidisciplinary and will utilize methods from the fields of molecular biology, immunochemistry and phsyiology. Transcriptional and translational control mechanisms will be investigated utilizing CDNA probes and immunoprecipitation procedures to quantitate ANF production in cultured atrial cardiocytes in response to specific stimuli. Immunochemical techniques will be developed to measure ANF levels in plasma and to determine the structure of the stored, secreted and circulating forms. Intact animal studies, in particular the conscious instrumented dog, will allow us to relate changes in ANF synthesis (i.e. transcriptional and translational regulation) and release to specific physiological manipulations, including the development of perinephritic hypertension, as well as to define the neural, vascular and humoral factors that regulate these processes. Similarly, stu7dies in humans will be initiated to define the role of ANF in maintaining volume and pressure homeostasis. These studies will also form the basis for identifying potential diseases that ;may represent abnormalities in the genetic regulation of ANF production. In particular, the method of restriction fragment length analysis to define polymorphisms in the ANF gene or in its vicinity will be utilized to identify potential linkage with particular disease states where such an abnormality might be predicted, such as Bartter's and Gordon's syndromes. These techniques will also be extended to test the hypothesis that a genetic abnormality in ANF expression may be involved in the etiology of certain forms of hypertension.

心房利钠因子（ANF）是最近发现的一种储存在

项目成果

Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes.

哇巴因诱导大鼠心房心肌细胞分泌心房钠尿因子。

• DOI: 10.1152/ajpendo.1988.255.3.e383
• 发表时间: 1988
• 期刊: The American journal of physiology
• 作者: Bloch,KD;Zamir,N;Lichtstein,D;Seidman,CE;Seidman,JG
• 通讯作者: Seidman,JG

cis-dominance of rat atrial natriuretic factor gene regulatory sequences in transgenic mice.

转基因小鼠中大鼠心房钠尿因子基因调控序列的顺式显性。

• DOI: 10.1139/y91-223
• 发表时间: 1991
• 期刊: Canadian journal of physiology and pharmacology
• 影响因子: 2.1
• 作者: Seidman,CE;Schmidt,EV;Seidman,JG
• 通讯作者: Seidman,JG

Analysis of atrial natriuretic factor biosynthesis and secretion in adult and neonatal rat atrial cardiocytes.

成年和新生大鼠心房心肌细胞心房钠尿因子生物合成和分泌的分析。

• DOI: 10.1016/0024-3205(87)90748-x
• 发表时间: 1987
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Zisfein,JB;Sylvestre,D;Homcy,CJ;Graham,RM
• 通讯作者: Graham,RM

Characterization and purification of a protease in serum that cleaves proatrial natriuretic factor (ProANF) to its circulating forms.

血清中一种蛋白酶的表征和纯化，该蛋白酶可将心房钠尿因子 (ProANF) 裂解为其循环形式。

• DOI: 10.1021/bi00400a030
• 发表时间: 1987
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Zisfein,JB;Graham,RM;Dreskin,SV;Wildey,GM;Fischman,AJ;Homcy,CJ
• 通讯作者: Homcy,CJ

Serum-mediated enhancement of ANF accumulation in the culture medium of cardiac atriocytes.

血清介导的心肌细胞培养基中 ANF 积累的增强。

• DOI: 10.1016/0006-291x(86)91070-3
• 发表时间: 1986
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Sylvestre,DL;Zisfein,JB;Graham,RM;Homcy,CJ
• 通讯作者: Homcy,CJ