Lifestyle modifications to prevent and control hypertension. 4. Recommendations on physical exercise training. Canadian Hypertension Society,Canadian Coalition for High Blood Pressure Prevention and Control,Laboratory Centre for Disease Control at Health Canada,Heart and Stroke Foundation of Canada

OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals concerning the effects of regular physical activity on the prevention and control of hypertension in otherwise healthy adults. OPTIONS: People may engage in no, sporadic or regular physical activity that may be of low, moderate or vigorous intensity. For sedentary people with hypertension, the options are to undertake or maintain regular physical activity and to avoid or moderate medication use; to use another lifestyle modification technique; to commence or continue antihypertensive medication; or to take no action and remain at increased risk of cardiovascular disease. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1997 with the terms exercise, exertion, physical activity, hypertension and blood pressure. Both reports of trials and review articles were obtained. Other relevant evidence was obtained from the reference lists of these articles, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: Physical activity of moderate intensity involving rhythmic movements with the lower limbs for 50-60 minutes, 3 or 4 times per week, reduces blood pressure and appears to be more effective than vigorous exercise. Harm is uncommon and is generally restricted to the musculoskeletal injuries that may occur with any repetitive activity. Injury occurs more often with jogging than with walking, cycling or swimming. The costs include the costs of appropriate shoes, garments and equipment, but these were not specifically measured. RECOMMENDATIONS: (1) People with mild hypertension should engage in 50-60 minutes of moderate rhythmic exercise of the lower limbs, such as brisk walking or cycling, 3 or 4 times per week to reduce blood pressure, (2) Exercise should be prescribed as an adjunctive therapy for people who require pharmacologic therapy for hypertension, especially those who are not receiving beta-blockers. (3) People who do not have hypertension should participate in regular exercise as it will decrease blood pressure and reduce the risk of coronary artery disease, although there is no direct evidence that it will prevent hypertension. VALIDATION: These recommendations agree with those of the World Hypertension League, the American College of Sports Medicine, the report of the US Surgeon General on physical activity and health, and the US National Institutes of Health Consensus Development Panel on Physical Activity and Cardiovascular Health. These guidelines have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.     

Detection of calcium-dependent regulatory protein binding components using 125I-labeled calcium-dependent regulatory protein.

The calcium-dependent regulatory protein (CDR) purified from bovine brain was iodinated with Na[125I]I using the lactoperoxidase-glucose oxidase system. The iodinated protein retained its ability to stimulate the Ca2+-sensitive CDR-depleted cyclic nucleotide phosphodiesterase from bovine heart. Stimulation of the phosphodiesterase by 125I-CDR was Ca2+-dependent and the labeled protein had a Ka for activation of cyclic nucleotide phosphodiesterase that was 4 times greater than unmodified CDR. 125I-CDR formed a Ca2+-dependent complex with the partially purified cyclic nucleotide phosphodiesterase which was detectable by autorradiography following electrophoresis of the complex on nondenaturing gels. This technique was used to detect CDR binding components in crude homogenates prepared from bovine heart and brain.     

Subcellular location of adenylate cyclase in rat cardiac muscle

Crude homogenates of rat cardiac muscle were fractionated in order to examine the subcellular location of adenylate cyclase in this tissue. The fractionation procedure employed differential centrifugation of homonized material, followed by collagenase treatment, centrifugation on a discontinuous sucrose density gradient and extraction with 1 M KCl. The particulate fraction obtained by this procedure contained a high specific activity and yield of adenylate cyclase, moderate levels of mitochondria and low levels of sarcoplasmic reticulum and contractile protein as judged by marker enzyme activities. Adenylate cyclase was purified 20-fold with a 33% yield from the crude homogenate, while mitochondrial, sarcoplasmic reticulum and contractile protein yields were 5, 0.4 and 0.7% respectively. The membrane fractions prepared in this manner were examined by sodium dodecyl sulfate · gel electrophoresis.Adenylate cyclase copurified with ouabain-sensitive (Na⁺ + K⁺)-ATPase, a plasma membrane marker enzyme, and not with Ca²⁺-accumulating activity, which is associated with the sarcoplasmic reticulum. The distribution of marker enzyme activities indicates that heart adenylate cyclase is not located in the sarcoplasmic reticulum but is localized predominantly, if not exclusively, in the plasma membrane.     

Liposomes and biotherapeutics

Application of liposomes as delivery system for biotherapeutic peptides and proteins may offer important therapeutic advantages over existing delivery methods. Several approaches towards achieving improved delivery of biotherapeutics with liposomes are outlined. Although the literature on this topic is sporadic and frequently incomplete, enough of a research foundation exists to justify the conclusion that liposomes can play an important role in the formulation and delivery of biotherapeutics. However, it will be necessary to understand more fully the mechanisms of action before optimum liposomal dosage forms can be designed.