Regulation of blood pressure by the type 1A angiotensin II receptor gene.

The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the physiological and genetic functions of the type 1A receptor for angiotensin II, we have disrupted the mouse gene encoding this receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in expected numbers, and the histomorphology of their kidneys, heart, and vasculature was normal. AT1 receptor-specific angiotensin II binding was not detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-) heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to approximately 50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1 mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar differences in blood pressure between the groups were seen when intraarterial pressures were measured by carotid cannulation. These studies demonstrate that type 1A angiotensin II receptor function is required for vascular and hemodynamic responses to angiotensin II and that altered expression of the Agtr1A gene has marked effects on blood pressures.

The First Century of Right to Arms Litigation

This Article examines state court cases involving the right to arms, during the first century following ratification of the Amendment in 1791. This is not the first article to survey some of those cases. This Article includes additional cases, and details the procedural postures and facts, not only the holdings. The Article closely examines how the Supreme Court integrated the nineteenth century arms cases into Heller and McDonald to shape modern Second Amendment law. Part I briefly explains two English cases which greatly influenced American legal understandings. Semayne’s Case is the foundation of “castle doctrine” — the right to home security which includes the right of armed self-defense in the home. Sir John Knight’s Case fortified the tradition of the right to bear arms, providing that the person must bear arms in a non-terrifying manner. Part II examines American antebellum cases; these are the cases to which Heller looked for guidance on the meaning of the Second Amendment. Part III looks at cases from Reconstruction and the early years of Jim Crow, through 1891. As with the antebellum cases, the large majority of post-war cases are from the Southeast, which during the nineteenth century was the region most ardent for gun control. The heart of gun control country was Tennessee and Arkansas; courts there resisted some infringements of the right to arms, but eventually gave up. Heller and McDonald did not look to the Jim Crow cases as constructive precedents on the Second Amendment.

A hipertensão pulmonar como consequência de lúpus na gravidez : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Interplay between cardiac function and heart development

Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Develomental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Stay young at heart /

"November 1994"--P. [4] of portfolio.

High blood pressure control : information and education strategies for messages to public and patient audiences.

Cover title.

National high blood pressure 12-month kit.

"May 1988."

Relief Well Rehabilitation Options in Chief Joseph Dam Right Abutment Drainage Tunnel

This report summarizes the data, observations, methods, assumptions, and decisions for the design of the Relief Well Rehabilitation Project in the Right Abutment Drainage Tunnel at Chief Joseph Dam. Chief Joseph Dam (CJD) is a dam on the Columbia River and is owned and operated by the U.S. Army Corps of Engineers (USACE). It is the second only to Grand Coulee dam as the largest producer of hydropower in the United States. The right abutment drainage tunnel contains wooden stave relief wells. Water flows from these wells which reduces the hydrostatic pressure in the right abutment of the dam. The 22 wells in the floor of the tunnel are 60 years old and are in need of rehabilitation. The objective of this project is to control the groundwater gradient, prevent the movement of sediment, stop total screen collapse, and prevent initiation of backwards erosion and piping in the abutment. The rehabilitation solution is to install new stainless steel screens into the existing wells, backfill the annular space between the old wooden screen and the new stainless steel screens with a 3/8-inch pea gravel filter pack, and install a new top cap to hold the new screen in place. This report documents the data, observations, and methods used to complete the final design. During tunnel inspections USACE geologists observed dislodged end plugs and evidence of sediment movement out of the formation. The relief wells have historically high flows between 6,000 gallons per minute (gpm) to 9,000 gpm. New screens are designed based on as-built data and historic tunnel flow. The new screens are 8-in diameter, 100 slot (0.10-inch) screens. We found that screen diameter and slot size would provide adequate transmitting capacity for most of the relief wells. The filter pack gradation is based on descriptions from foundation construction reports. I found that 3/8-inch pea gravel is appropriate for the abutment material. During design, I also considered an option to install the screens into the relief wells without filter pack. I eliminated this option because it did not meet our rehabilitation objective to prevent total failure of the wooden screens.

Cosegregation analysis of natriuretic peptide genes and blood pressure in the spontaneously hypertensive rat

1. The natriuretic peptide precursor A (Nppa) and B (Nppb) genes are candidate genes for hypertension and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). The purpose of the present study was to determine the role of the Nppa and Nppb genes in the development of hypertension in the SHR. 2. A cohort (n = 162) of F2 segregating intercross animals was established between strains of hypertensive SHR and normotensive Wistar-Kyoto rats. Blood pressure and heart weight were measured in each rat at 12-16 weeks of age. Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker. The phenotype values were compared with genotype using the computer package MAP-MAKER 3.0 (Whitehead Institute, Boston, MA, USA) to determine whether there was a link between the genetic variants of the natriuretic peptide family and blood pressure or cardiac hypertrophy. 3. A strong correlation was observed between the Nppa marker and blood pressure. A quantitative trait locus (QTL) for blood pressure on chromosome 5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM from the Nppa locus. The linkage score for the blood pressure QTL on chromosome 5 was 3.8 and the QTL accounted for 43% of the total variance of systolic blood pressure, 54% of diastolic blood pressure and 59% of mean blood pressure. No association was found between the Nppb gene and blood pressure. This is the first report of linkage between the Nppa marker and blood pressure in the rat. There was no correlation between the Nppa or Nppb genes or other markers in this region and either heart weight or left ventricular weight in F2 rats. 4. These findings suggest the existence of a blood pressure-dependent Nppa marker variant or a gene close to Nppa predisposing to spontaneous hypertension in the rat. It provides a strong foundation for further detailed genetic studies in congenic strains, which may help to narrow down the location of this gene and lead to positional cloning.

Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart

Objective: This study investigated signaling pathways that may contribute to the potent positive inotropic effect of human urotensin-II (hU-II) in human isolated right atrial trabeculae obtained from patients with coronary artery disease. Methods: Trabeculae were set up in tissue baths and stimulated to contract at 1 Hz. Tissues were incubated with 20 nM hU-II with or without phorbol 12-myristate 13-acetate (PMA, 10 muM) to desensitize PKC, the PKC inhibitor chelerythrine (10 muM), 10 muM 4alpha-phorbol that does not desensitize PKC, the myosin light chain kinase inhibitor wortmannin (50 nM, 10 muM), or the Rho kinase inhibitor Y-27632 (0.1 - 10 muM). Activated RhoA was determined by affinity immunoprecipitation, and phosphorylation of signaling proteins was determined by SDS-PAGE. Results: hU-II caused a potent positive inotropic response in atrial trabeculae, and this was concomitant with increased phosphorylation of regulatory myosin light chain (MLC-2, 1.8 +/- 0.4-fold, P < 0.05, n = 6) and PKCalpha/betaII (1.4 +/- 0.2-fold compared to non-stimulated controls, P < 0.05, n = 7). Pretreatment of tissues with PMA caused a marked reduction in the inotropic effect of hU-II, but did not affect hU-II-mediated phosphorylation of MLC-2. The inotropic response was inhibited by chelerythrine, but not 4alpha-phorbol or wortmannin. Although Y-27632 also reduced the positive inotropic response to hU-II, this was associated with a marked reduction in basal force of contraction. RhoA. GTP was immunoprecipitated in tissues pretreated with or without hU-II, with findings showing no detectable activation of RhoA in the agonist stimulated tissues. Conclusions: The findings indicated that hU-II increased force of contraction in human heart via a PKC-dependent mechanism and increased phosphorylation of MLC-2, although this was independent of PKC. The positive inotropic effect was independent of myosin light chain kinase and RhoA-Rho kinase signaling pathways. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure

Background - Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. Methods and Results - Thirty medically treated ambulatory hypertensive patients (19 women, age 62 +/- 6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A 250m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31 +/- 5 kg/m(2)) with reduced treadmill exercise capacity (6.7 +/- 2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133 +/- 17/80 +/- 7mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57 +/- 0.46 s(-1) versus 6-months: -1.91 +/- 0.36 s(-1), P < 0.01), peak systolic strain (-20.3 &PLUSMN; 5.0% versus -26.9 &PLUSMN; 4.3%, P < 0.001), and CVIB (7.4 +/- 1.7dB versus 8.6 +/- 1.7 dB, P = 0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P = 0.05, P = 0.02, and P = 0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P = 0.04) and a trend to reduced left atrial area (P = 0.09). Conclusions - Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Response of B-type natriuretic pepticle to exercise in hypertensive patients with suspected diastolic heart failure: Correlation with cardiac function, hemodynamics, and workload

Background Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Methods Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (So) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Results Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 57 to 74 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise So, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Conclusions Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.

Evidence for endothermic ancestors of crocodiles at the stem of archosaur evolution

Physiological, anatomical, and developmental features of the crocodilian heart support the paleontological evidence that the ancestors of living crocodilians were active and endothermic, but the lineage reverted to ectothermy when it invaded the aquatic, ambush predator niche. In endotherms, there is a functional nexus between high metabolic rates, high blood flow rates, and complete separation of high systemic blood pressure from low pulmonary blood pressure in a four-chambered heart. Ectotherms generally lack all of these characteristics, but crocodilians retain a four-chambered heart. However, crocodilians have a neurally controlled, pulmonary bypass shunt that is functional in diving. Shunting occurs outside of the heart and involves the left aortic arch that originates from the right ventricle, the foramen of Panizza between the left and right aortic arches, and the cog-tooth valve at the base of the pulmonary artery. Developmental studies show that all of these uniquely crocodilian features are secondarily derived, indicating a shift from the complete separation of blood flow of endotherms to the controlled shunting of ectotherms. We present other evidence for endothermy in stem archosaurs and suggest that some dinosaurs may have inherited the trait.

Survey of intensive care nurses' knowledge relating to the pulmonary artery catheter

In 2003 there was an increase in the use of pulmonary artery catheters in Australia from 12, 000 to 16, 000 units in intensive care and peri-operative care. This survey of intensive care nurses in five intensive care units in Queensland addressed knowledge of use, safety and complications of the pulmonary artery catheter, using a previously validated 31 question multiple choice survey. One hundred and thirty-nine questionnaires were completed, a response rate of 46%. The mean score was 13.3, standard deviation +/-4.2 out of a total of 31 (42.8% correct). The range was 4 to 25. Scores were significantly higher in those participants with more ICU experience, higher nursing grade, a higher self-assessed level of knowledge and greater frequency of PAC supervision. There was no significant correlation between total score and hospital- or university-based education, or total score and public or private hospital participants. Fifty-one per cent were unable to correctly identify the significant pressure change as the catheter is advanced from the right ventricle to the pulmonary artery.

Fetal echocardiography: are we getting it right?

Objective To determine the diagnostic accuracy of prenatal fetal echocardiography. Methods The study was a retrospective chart review of 190 consecutive patients over a 3-year period from November 1998 to February 2002 of all women referred to the Maternal Fetal Medicine unit, Mater Mothers Hospital, for fetal echocardiography. The prenatal diagnosis was compared with the postnatal diagnosis made by postnatal echocardiography, surgical findings or post-mortem. The accuracy of prenatal diagnosis was described on a predetermined 4-point scale. Results Of the 89 patients, for whom complete diagnostic follow-up was available, there was complete agreement between the prenatal and postnatal diagnosis in 63 cases, minor discrepancies in 25 cases and major disagreement in 1 case. Conclusions In experienced hands, fetal echocardiography is accurate and allows medical staff and patients information in order manage a pregnancy appropriately. Copyright (C) 2004 John Wiley Sons, Ltd.