Hypertension: Journal of the American Heart Association最新文献

{"title":"Bradykinin Improves Left Ventricular Diastolic Function Under Long-Term Angiotensin-Converting Enzyme Inhibition in Heart Failure","authors":"M. Fujii, A. Wada, T. Tsutamoto, M. Ohnishi, T. Isono, M. Kinoshita","doi":"10.1161/01.HYP.0000015613.78314.9E","DOIUrl":"https://doi.org/10.1161/01.HYP.0000015613.78314.9E","url":null,"abstract":"Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P <0.01), prolonged the time constant of relaxation (P <0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca2+-ATPase mRNA (P <0.05). FR173657 also upregulated collagen type I and III mRNA (P <0.05) and increased the total amount of cardiac collagen deposits (P <0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca2+ handling and suppression of collagen accumulation.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"46 1","pages":"952-957"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88152700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Transfer of Hepatocyte Growth Factor to Subarachnoid Space in Cerebral Hypoperfusion Model","authors":"S. Yoshimura, R. Morishita, K. Hayashi, J. Kokuzawa, M. Aoki, Kunio Matsumoto, Toshikazu Nakamura, T. Ogihara, N. Sakai, Y. Kaneda","doi":"10.1161/01.HYP.0000017553.67732.E1","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017553.67732.E1","url":null,"abstract":"Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that &bgr;-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using &bgr;-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P <0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P <0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P <0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P <0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"20 1","pages":"1028-1034"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88390990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse","authors":"P. Lantelme, A. Rohrwasser, B. Gociman, E. Hillas, T. Cheng, Gray Petty, Jennifer Thomas, S. Xiao, T. Ishigami, Tracy Herrmann, D. Terreros, K. Ward, J. Lalouel","doi":"10.1161/01.HYP.0000016177.20565.A0","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016177.20565.A0","url":null,"abstract":"Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"124 1 1","pages":"1007-1014"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85202500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validity and Reliability of Diastolic Pulse Contour Analysis (Windkessel Model) in Humans","authors":"T. S. Manning, B. Shykoff, J. Izzo","doi":"10.1161/01.HYP.0000016920.96457.7C","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016920.96457.7C","url":null,"abstract":"The present study assessed (1) the impact of the measurement site (lower versus upper extremity) on the corresponding compliance variables and (2) the overall reliability of diastolic pulse contour (Windkessel-derived) analysis in normal and hypertensive subjects. Arterial tonograms were recorded in the supine position from the radial and posterior tibial arteries in 20 normotensive (116±12/68±8 mm Hg) and 27 essential hypertensive subjects (160±16/94±14 mm Hg). Ensemble-averaged data for each subject were fitted to a first-order lumped-parameter model (basic Windkessel) to compute whole-body arterial compliance (CA) and to a third-order lumped-parameter model (modified Windkessel) to compute proximal compliance (C1) and distal compliance (C2). Despite high-fidelity waveforms in each subject, the first-order Windkessel model did not yield interpretable (positive) values for CA in 50% of normotensives and 41% of hypertensives, whereas the third-order model failed to yield interpretable C1 or C2 results in 15% of normotensives and 41% of hypertensives. No between-site correlations were found for the first-order time constant, 2 of the 3 third-order model curve-fitting constants, or CA, C1, or C2 (P >0.50). Mean values for all 3 compliance variables were higher for the leg than the arm (P <0.05 each). We conclude that differences in Windkessel-derived compliance values in the arm and leg invalidate whole-body model assumptions and suggest a strong influence of regional circulatory properties. The validity and utility of Windkessel-derived variables is further diminished by the absence of between-site correlations and the common occurrence of uninterpretable values in hypertensive subjects.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"53 1","pages":"963-968"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90927967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eight-Year Blood Pressure Change in Middle-Aged Men: Relationship to Multiple Nutrients","authors":"J. Stamler, Kiang Liu, K. Ruth, J. Pryer, P. Greenland","doi":"10.1161/01.HYP.0000016178.80811.D9","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016178.80811.D9","url":null,"abstract":"Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"93 1","pages":"1000-1006"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79016573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Mild Exercise on Insulin Sensitivity in Hypertensive Subjects","authors":"Caroline Rhéaume, P. Waib, Y. Lacourciére, A. Nadeau, J. Cléroux","doi":"10.1161/01.HYP.0000016921.50185.7B","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016921.50185.7B","url":null,"abstract":"Physical exercise increases insulin sensitivity in conditions associated with insulin resistance, such as obesity and diabetes, but little is known in this regard in hypertension. Whether postexercise changes in hemodynamics and/or changes in insulin-induced vasodilatation could contribute to a postexercise increase in insulin sensitivity in hypertensive subjects is unknown. We investigated the effects of acute physical exercise on insulin sensitivity in 10 hypertensive and 10 normotensive subjects during a control evaluation (CTRL), during lower body negative pressure (LBNP), after 30 minutes of mild bicycle exercise (POSTEX), and during LBNP after exercise (POSTEX+LBNP). Insulin-induced vasodilatation was assessed from peak forearm blood flow during the intravenous glucose tolerance test. Cardiac output (4.9±0.3 versus 5.3±0.4 L/min, mean±SEM) and insulin sensitivity (the glucose disappearance rate over insulin area under the curve: 0.91±0.07 versus 1.38±0.25 min−1/[pmol · L−1] · minute) were lower (both P <0.05) in hypertensive than in normotensive subjects, respectively. Cardiac output decreased during LBNP, increased during POSTEX, and was similar to control during POSTEX+LBNP in both groups. Insulin sensitivity was unchanged during LBNP, increased during POSTEX, and remained elevated during POSTEX+LBNP in hypertensive subjects, whereas it remained unchanged in normotensives. Peak forearm blood flow was significantly lower in hypertensive than in normotensive subjects, despite higher insulin levels in hypertensives, and was not modified by LBNP or exercise. In conclusion, insulin sensitivity increases after exercise in hypertensive subjects, and the increase in cardiac output does not contribute to this effect. Endogenous insulin-induced vasodilatation is reduced in hypertensive subjects, and this insulin action is not affected by physical exercise.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"23 1","pages":"989-995"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72923664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma ProANP1–30 Reflects Salt Sensitivity in Subjects With Heredity for Hypertension","authors":"O. Melander, E. Frandsen, L. Groop, U. Hulthén","doi":"10.1161/01.HYP.0000017552.91014.2A","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017552.91014.2A","url":null,"abstract":"The aim of the present study was to investigate whether plasma concentration of proANP1–30, the N-terminal fragment of the atrial natriuretic peptide prohormone, or 24-hour urinary excretion of urodilatin reflects the degree of salt sensitivity in hypertension-prone individuals. Plasma concentration of proANP1–30 and urinary urodilatin excretion were determined at baseline, after 1 week on a low-salt diet (10 mmol/d) and after another week on a high-salt diet (240 mmol/d) in 30 healthy subjects with heredity for hypertension. Salt sensitivity was defined as the difference between mean arterial blood pressure after the high-salt diet and the mean arterial blood pressure after the low-salt diet. High- versus low-salt intake increased proANP1–30 (668±330 versus 358±150 pmol/L;P <0.00001) and urodilatin (18.7±5.2 versus 16.0±8.3 pmol/24 h;P <0.05). ProANP1–30 correlated with salt sensitivity at baseline (r =0.76, P <0.000001), after the low- (r =0.80, P <0.0000001) and high-salt diets (r =0.85, P <0.00000001). The increase in proANP1–30 induced by changing from the low- to the high-salt diet was also directly related to salt sensitivity (r =0.78, P <0.000001). ProANP1–30 was not related to urinary sodium excretion. Neither urodilatin nor the sodium-induced change in urodilatin correlated with salt sensitivity. However, urodilatin was related to the urinary sodium excretion at baseline (r =0.58, P <0.01) and after the high-salt diet (r =0.62, P <0.001). In conclusion, the close correlations between proANP1–30 and salt sensitivity suggest that proANP1–30 may serve as a marker for salt sensitivity and could be useful in identifying subjects who would benefit from dietary salt restriction to prevent development of hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"97 1","pages":"996-999"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83089156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin 1-9 and 1-7 Release in Human Heart: Role of Cathepsin A","authors":"H. Jackman, M. Massad, M. Sekosan, F. Tan, V. Brovkovych, B. Marcic, E. G. Erdös","doi":"10.1161/01.HYP.0000017283.67962.02","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017283.67962.02","url":null,"abstract":"Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A’s presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B2 receptor in Chinese hamster ovary cells transfected to express human ACE and B2 (CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B2 receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC50s) with ACE. They probably induce conformational changes in the ACE/B2 receptor complex via interaction with ACE.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"107 1","pages":"976-981"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76246741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistant Hypertension: Comparing Hemodynamic Management to Specialist Care","authors":"S. Taler, S. Textor, J. Augustine","doi":"10.1161/01.HYP.0000016176.16042.2F","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016176.16042.2F","url":null,"abstract":"Although resistant hypertension affects a minority of all hypertensives, this group continues to experience disproportionately high cardiovascular event rates despite newer antihypertensive agents. Hypertension represents an imbalance of hemodynamic forces within the circulation, usually characterized by elevated systemic vascular resistance. We studied the utility of serial hemodynamic parameters in the selection and titration of antihypertensive medication in resistant hypertensive patients using highly reproducible noninvasive measurements by thoracic bioimpedance. Resistant hypertension patients (n=104) were randomized to drug selection based either on serial hemodynamic (HD) measurements and a predefined algorithm or on drug selection directed by a hypertension specialist (SC) in a 3-month intensive treatment program. Blood pressure was lowered by intensified drug therapy in both treatment groups (169±3/87±2 to 139±2/72±1 mm Hg HD versus 173±3/91±2 to 147±2/79±1 mm Hg SC, P <0.01 for systolic and diastolic BP), using similar numbers and intensity of antihypertensive medications. Blood pressures were reduced further for those treated according to hemodynamic measurements, resulting in improved control rates (56% HD versus 33% SC controlled to ≤140/90 mm Hg, P <0.05) and incremental reduction in systemic vascular resistance measurements. Although the number of patients taking diuretics did not differ between groups, final diuretic dosage was higher in the hemodynamic cohort. Our results demonstrate superior blood pressure control using a treatment algorithm and serial hemodynamic measurements compared with clinical judgment alone in a randomized prospective study. Our measurements of thoracic fluid volume support occult volume expansion as a mediator of antihypertensive drug resistance and use of impedance measurements to guide advancing diuretic dose and adjustment of multidrug antihypertensive treatment.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"70 1","pages":"982-988"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86248553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Pressure–Independent Attenuation of Cardiac Hypertrophy by AT1R-AS Gene Therapy","authors":"A. Pachori, M. Numan, C. Ferrario, D. Diz, M. Raizada, M. Katovich","doi":"10.1161/01.HYP.0000017827.63253.16","DOIUrl":"https://doi.org/10.1161/01.HYP.0000017827.63253.16","url":null,"abstract":"Our studies have established that a single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense gene causes prolonged antihypertensive actions in the spontaneously hypertensive rat. These results suggest that antisense gene therapy is a conceptually valid strategy for the control of hypertension at the genetic level. To evaluate whether attenuation of the pathophysiological aspects of hypertension are dependent on the blood pressure lowering actions of antisense gene therapy, we chose the renin transgenic rat as a hypertensive animal model and cardiac hypertrophy as the hypertension-associated pathophysiology. A single intracardiac administration of the retroviral vector containing angiotensin II type I receptor antisense in the neonatal rat resulted in long-term expression of the antisense transgene in various cardiovascular-relevant tissues, including the heart. This expression was associated with a significant attenuation of cardiac hypertrophy despite its failure to normalize high blood pressure. Developmental studies indicated that cardiac hypertrophy was evident as early as 16 days of age in viral vector–treated control transgenic rats, despite these animals exhibiting normal blood pressure. These observations demonstrate that, in the renin-transgenic rat, the onset of cardiac hypertrophy occurs during development and is prevented without normalization of high blood pressure. Collectively, these results provide further proof of the concept and indicate that antisense gene therapy could successfully target the local tissues’ renin-angiotensin system to produce beneficial cardiovascular outcomes.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"19 1","pages":"969-975"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88113212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}