Modulation of susceptibility to HIV-1 infection by the cytotoxic T lymphocyte antigen 4 costimulatory molecule.

CD4 T cells activated in vitro by anti-CD3/28-coated beads are resistant to infection by CC chemokine receptor 5 (CCR5)-dependent HIV-1 isolates. In vivo, antigen-presenting cells (APCs) activate CD4 T cells in part by signaling through the T cell receptor and CD28, yet cells stimulated in this manner are susceptible to HIV-1 infection. We show that cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement counteracts the CD28 antiviral effects, and that the ratio of CTLA-4 to CD28 engagement determines the susceptibility of HIV-1 infection. Furthermore, unopposed CTLA-4 signaling provided by CD28 blockade promotes vigorous HIV-1 replication, despite minimal T cell proliferation. Finally, CTLA-4 antibodies decrease the susceptibility of antigen-activated CD4 T cells to HIV, suggesting a potential approach to prevent or limit viral spread in HIV-1-infected individuals.

Productive infection of neonatal CD8+ T lymphocytes by HIV-1.

CD8+ T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here we report that activated neonatal CD8+ T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whereas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta+ CD4- T cell receptor-alpha/beta+ neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1-activated cord blood CD8+ T cells coexpress CD4, the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8+ T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation.

Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation.

Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.

Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells.

Activation of CD4(+) T lymphocytes from human immunodeficiency virus-type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage-tropic HIV-1. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals.

Human biodistribution of 111In-labeled B72.3 monoclonal antibody.

The murine IgG1 monoclonal antibody B72.3 reacts with human colorectal, breast, lung, pancreatic, gastric, and ovarian tumors. Human biodistribution studies using intact 131I-B72.3 have been reported by Carrasquillo et al. (J. Nucl. Med., 29: 1022-1030, 1988). We have performed similar studies on five patients using i.v. infusion of 20 mg of intact 111In-B72.3 (Cytogen Corp.). Serum clearance is similar with a t1/2 of 64.2 h (range, 44-80) for 111In-B72.3 and 65 h (range, 32-106) for 131I-B72.3 (J. A. Carrasquillo et al., J. Nucl. Med., 29: 1022-1030, 1988). However, organ biodistribution is markedly different. For 131I-B72.3, hepatic and splenic clearance mirrors blood pool clearance (J. A. Carrasquillo et al., J. Nucl, Med., 29: 1022-1030, 1988). For 111In-B72.3, there is rapid uptake in tumor, liver, spleen, kidney, lumbar spine, and testes by 2-6 h with no significant clearance over the next 9 days. For 111In-B72.3, quantitative analysis of liver (from biopsy specimens), spleen, kidney, and lumbar spine (from scintiphoto regions of interest after background subtraction and attenuation correction) shows the following peak organ biodistributions in percentage infused dose: liver, 32%; spleen, 3.9%; kidneys, 3.5%; and lumbar vertebral bodies (marrow sample), 2.7%. For both 111In-B72.3 and 131I-B72.3, the principal route of excretion from the body is urinary with excretion rate of 131I faster than 111In. The marked differences between 111In-B72.3 and 131I-B72.3 biodistribution and clearance strongly influence the dosimetry, immunodetection, and immunotherapeutic potentials of B72.3 MoAb.

Chronic potentiation of vasoconstrictor hypertension by adrenocorticotropic hormone.

The chronic effects of ACTH on mean arterial pressure (MAP) and related variables were studied in dogs with both chronic norepinephrine (NE)- and chronic aldosterone-induced hypertension. MAP was recorded continuously for 24 hours/day, and sodium intake was 71 mEq/day. ACTH was infused for 8 days at a rate that does not increase MAP in normotensive dogs and yet a rate that produces pronounced mineralocorticoid and glucocorticoid effects. Chronic ACTH infusion in dogs with NE hypertension caused natriuresis, kaliuresis, diuresis, hypernatremia, hypokalemia, and suppression of PRA; additionally, there was either no net change in water balance or net water balance was positive. However, in marked contrast to dogs without pre-existing hypertension, in dogs with NE hypertension ACTH produced a pronounced additional increase in MAP of 39 to 63 mm Hg. Although ACTH markedly potentiated NE hypertension, high infusion rates of aldosterone (+6 mm Hg) and cortisol (-7 mm Hg) had relatively weak effects on MAP; further, in dogs with NE hypertension, the increase in MAP associated with simultaneous infusions of high rates of cortisol and aldosterone was equal to only approximately half of that produced by ACTH. In dogs with aldosterone hypertension, the changes in salt and water balance produced by ACTH were comparable to those that occurred when ACTH was administered to dogs with NE hypertension. In dogs with aldosterone hypertension, however, ACTH did not produce kaliuresis, hypernatremia, or hypokalemia; moreover, ACTH did not exacerbate aldosterone hypertension. Thus, the data indicate that the hypertensive effects of ACTH are manifested in conditions of reduced renal excretory capacity such as exist when plasma levels of the potent sodium -retaining hormone NE are inappropriately elevated. Finally, the hypertensive effects of ACTH cannot be accounted for simply on the basis of enhanced mineralocorticoid and glucocorticoid activity.

Chronic angiotensin II infusion decreases renal norepinephrine overflow in conscious dogs.

Sympathetic nerve activity and in particular renal sympathetic nerve activity were monitored in six conscious dogs subjected to 6 days of intravenous angiotensin (ANG II) infusion (20 ng/kg/min). This was accomplished by measurement of both arterial and renal venous plasma catecholamine concentration. During the initial 4 hours of ANG II infusion, mean arterial pressure (MAP) increased 35 +/- 8 mm Hg from a control value of 101 +/- 4 mm Hg. Although there were no significant changes in arterial plasma norepinephrine (NE) concentration at this time (control = 148 +/- 40 pg/ml), arterial plasma epinephrine (E) concentration increased threefold (control 42 +/- 15 pg/ml). After 24 hours of ANG II infusion, MAP remained elevated (132 +/- 5 mm Hg), but plasma E concentration returned to control levels. From Days 2 through 6 of ANG II infusion, MAP was elevated approximately 40 mm Hg, but there were no chronic increases in either arterial plasma E or NE concentrations. In contrast to arterial plasma catecholamine concentration, renal vein plasma NE concentration (control = 216 +/- 27 pg/ml) actually decreased during both the acute (122 +/- 12 pg/ml) and chronic (103 +/- 26 pg/ml) phases of ANG II infusion. Moreover, renal NE overflow (renal venous plasma NE concentration-arterial plasma NE concentration X effective renal plasma flow), an index of renal sympathetic nerve activity, was depressed during the chronic phase of ANG II hypertension. These results, therefore, do not support the contention that the sympathetic nervous system mediates the hypertension produced by elevated plasma levels of ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the renal nerves in one-kidney, one clip hypertension in rats.

The effects of renal denervation on the onset and maintenance of one-kidney, one clip Goldblatt (1K1C) hypertension were determined. Renal denervation was performed at the time of 1K1C surgery, and was repeated at 3-week intervals to prevent renal nerve regeneration. Denervation delayed the onset of 1K1C hypertension by about 5 weeks, but the final hypertensive state was unaltered. Mean arterial pressure (MAP) averaged 196 +/- 11.4 mm Hg in six rats at 9 weeks after 1K1C surgery and 194 +/- 11.3 mm Hg in eight renal-denervated rats at this time. The delay in the development of 1K1C hypertension following renal denervation could not be explained by interference with renin release. This delay in the development of hypertension could be prevented, however, in renal-denervated 1K1C rats by substituting saline for the drinking water. Two weeks after 1K1C surgery and a high sodium diet, MAP averaged 164 +/- 6.4 mm Hg in eight rats rats with intact renal nerves and 173 +/- 4.8 mm Hg in nine renal-denervated rats. Intact renal nerves are not necessary for the development or maintenance of 1K1C hypertension. Renal denervation delays development of 1K1C hypertension, possibly by delaying the ability of these rats to retain sodium.

Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.

Sentinel lymph node localization in early breast cancer.

METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.

Signal transduction through crosslinking CD7 and IgM-Fc receptors that inhibits T-cell proliferation.

We have previously suggested a possible involvement of CD7 and/or the putative receptor for IgM-Fc (FcRmu) in the downregulation of T-cell responses to mitogen and alloantigen. In this report, we examined the effect of ligand-receptor interaction upon T-cell proliferation by using anti-CD7 monoclonal antibodies (mAbs) and purified human IgM (HIgM) and showed that crosslinking CD7 and/or FcRmu on T cells resulted in significant inhibition of mitogen- and alloantigen-induced proliferative responses. In most cases, crosslinking of FcRmu alone or together with CD7 receptors on peripheral blood lymphocytes (PBLs) resulted in more potent suppression of T-cell proliferation than that caused by crosslinking CD7 alone. Examination of potential inhibitory mechanisms revealed that crosslinking CD7 and FcRmu does not reduce cell viability or the expression of T-cell markers that are important for T-cell activation or proliferation. However, crosslinking CD7 and/or FcRmu of PBLs significantly reduced phytohemagglutinin (PHA)-induced IL-2 production and rendered PBLs unable to utilize exogenously added human recombinant IL-2 (rIL-2). Further examination of possible signal transduction that might be associated with crosslinking CD7 and/or FcRmu receptors indicated a marked reduction in the magnitude and duration of intracellular calcium (Ca++)i released in response to PHA. These findings suggest that crosslinking CD7 and FcRmu inhibits T-cell activation and proliferation by a calcium-dependent mechanism that inhibits IL-2 production and/or utilization.

The relationship of head and neck irradiation to the subsequent development of thyroid neoplasms.

Individuals who have received head and neck radiation for benign conditions have a markedly increased risk of developing thyroid, salivary, and perhaps breast cancer as compared to the general population. Although the relative risk is very high, the absolute risk that any one individual who has had head or neck irradiation will develop a subsequent malignancy is low. Identification of these patients through some type of screening procedure may be beneficial in terms of prevention of subsequent morbidity and perhaps mortality from cancer, especially thyroid and salivary cancer. The risks of any detection or prophylaxis program must be carefully weighed against the probable, but unproved benefits of early detection. A major unresolved question is the natural history of microscopic thyroid carcinoma in the 25 yr-40 yr old radiation exposed population.

Influenza virus upregulates CXCR4 expression in CD4+ cells.

We examined the effect of prior influenza virus infection on the susceptibility of CD4+ cells to HIV-1 infection. Influenza virus infection of HeLa-CD4 cells resulted in a marked increase in susceptibility to infection by CXCR4-dependent but not CCR5-dependent HIV isolates. Influenza virus infection resulted in an increase in the steady state level of CXCR4 transcripts and an increase in cell surface CXCR4 expression. Our observations suggest that infectious agents such as influenza may contribute to HIV disease progression by modulating coreceptor availability.

Fluorescent monitoring of Jurkatt cell intracellular magnesium during metabolic poisoning.

Divalent cation movement characterizes the final common pathway of cellular death from ischemic or metabolic injury. The influx of calcium is an essential step in cellular death. We hypothesized that intracellular magnesium levels may change during the progression to cellular death. Verapamil-sensitive changes in free ionized intracellular Mg2+ ([Mg2+[i) and Ca2+ ([Ca2+]i) levels were estimated in transformed T-lymphocytes exposed to metabolic inhibitors. Separate experiments used a Mg(2+)-sensitive fluoroprobe, fura-2 (Ex 1,344, Ex 2,376, Em 500), and a Ca(2+)-sensitive fluoroprobe, fura-2 (Ex 1,340, Ex 2,380, Em 510). Chemical anoxia (sodium cyanide 1 mM, iodoacetic acid 10 mM) caused a gradual increase in [Ca2+]i (control 126 +/- 13 nM) to > 1 mM by 10 min. This increase in [Ca2+]i was not affected by verapamil treatment. In separate experiments, [Mg2+]i levels were monitored during chemical anoxia. The specificity of mag-fura for Mg2+ over Ca2+ was reflected in the absence of a response to the lymphocyte Ca2+ mobilizer OKT-3. Uncorrected control [Mg2+]i levels (.4 +/- .1 mM) were not affected by the combined cyanide-iodoacetate treatment. A small increase in mag-fura-2 fluorescence was noted, probably due to binding of Ca2+ to the fluoroprobe when [Ca2]i exceeded 1 mM. Elimination of Ca2+ from the extracellular buffer increased the resting estimate of intracellular [Mg2+] to 1.6 + .1 mM. These results indicate that 1) extracellular Ca2+ can interfere with the fluorescent determination of intracellular magnesium concentration, and 2) intracellular free Mg2+ concentrations do not change in this cell line during chemical anoxia.

Reduced oxygen consumption precedes the drop in body core temperature caused by hemorrhage in rats.

This study examines the early time course in core temperature change and oxygen consumption at 4 levels of hemorrhage. Chronically instrumented rats were acclimatized to a respirometry chamber for 30 min. The rats were briefly (10 min) removed from the chamber for a fixed volume hemorrhage of 0 mL/kg (sham), 8 mL/kg, 16 mL/kg, 24 mL/kg, or 32 mL/kg. Rats were then returned to the chamber, and oxygen consumption and body core temperature were monitored for the next 2 h. Oxygen consumption (control 1.26 mL O2/g/h) fell significantly 5 min after hemorrhage in all but the sham and 8 mL/kg hemorrhage groups, with the decrease proportional to the hemorrhage volume. The 32 mL/kg hemorrhage group showed the greatest decrease, to 0.47 mL O2/g/h. Body core temperature (control 37.5 degrees C) fell more gradually, declining to 35.6 degrees C 110 min after the 24 mL/kg hemorrhage, and to 33.2 degrees C at 6 h after the 32 mL/kg hemorrhage. In the 16 mL/kg hemorrhage group, oxygen consumption fell significantly by 5 min after hemorrhage, but a drop in body temperature was not seen until 25 min after hemorrhage. The data from this study indicate that the drop in core temperature does not cause the observed decrease in oxygen consumption. In fact, the timing and magnitude of the drop in oxygen consumption indicate that the reduced metabolic rate may mediate the hemorrhage-induced drop in body core temperature in conscious rats.

Characterization of a Human Stromal Cell Line Supporting Hematopoietic Progenitor Cell Proliferation: Effect of HIV Expression.

Our objective was to determine the role that bone marrow-derived stromal cells have on human hematopoiesis in HIV infection. In particular, we dissected the heterogeneous bone marrow microenvironment to study the effect HIV expression might have on the cell population capable of producing the cytokines which will support human CD34+ cell differentiation. A stromal cell line, Lof(11-10), was established from human bone marrow by transfecting a plasmid containing the SV40 large T-antigen and isolating foci exhibiting a transformed phenotype. The Lof(11-10) cell line was characterized to determine its susceptibility to HIV infection, to identify its cytokine production profile, and to test the ability of conditioned media from this line to support CD34+ cell differentiation in the presence and absence of HIV expression. Nine cytokines were detected by RT-PCR and ELISA analysis. Conditioned media obtained from the Lof(11-10) cell line was able to support CD34+ celle differentiation. However, because the Lof(11-10) cells are not infectible by HIV, molecular clones of HIV were introduced into these cells by transfection. There was no qualitative difference in the levels of cytokine production between HIV-expressing and control Lof(11-10) cells. Furthermore, conditioned media derived from HIV-expressing and control Lof(11-10) cells added to bone marrow-derived CD34+ progenitor cells yielded similar colony formation in methylcellulose assays. Our data suggest that HIV infection of the cytokine-producing cells within the bone marrow microenvironment, as represented by the Lof(11-10) cell line, results in both normal cytokine production and hematopoiesis in spite of HIV expression. This report adds to the evidence against stromal cells being a significant target of HIV and establishes a system for comparison with more relevant models. Copyright 1995 S. Karger AG, Basel

Intraoperative gamma detection probe with presurgical antibody imaging in colon cancer.

In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In-MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In-MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In-MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake.

Cerebral infarction: diagnosis and assessment of prognosis by using 123IMP-SPECT and CT.

A multicenter prospective study was performed in 49 patients with 77 regions of cerebral infarction. Each patient was evaluated in the acute (0-5 days) and subacute (6-17 days) phases by (1) clinical neurologic examination, (2) CT scans, and (3) N-isopropyl-p-123I-iodoamphetamine (123IMP) single-photon emission CT (SPECT) scans. The abilities of the scans to (1) detect a lesion and (2) predict the clinical outcome were assessed. For lesion detection, 123IMP-SPECT was superior to CT in the first 2 days, but the scans were equally effective 3-5 days after onset. In the subacute phase, IV contrast-enhanced CT was superior to 123IMP-SPECT and unenhanced CT. The clinical outcome was only mildly correlated with the results of the acute and subacute 123IMP-SPECT and the acute CT scans. Reduction in lesion size on the subacute scans did not correlate with clinical improvement. We conclude that the parameters measured by CT and 123IMP-SPECT in patients with acute cerebral infarction cannot reliably be used to predict clinical outcome. 124I contamination of 123IMP and the use of low-energy collimators may have decreased lesion detectability.

Endurance exercise in mild hypertension: effects on blood pressure and associated metabolic and quality of life variables.

The effects of a ten week endurance exercise training programme on blood pressure and associated metabolic and quality of life variables were examined in 28 unmedicated mildly hypertensive men (21-54 years of age). At baseline, BP averaged 138.8/94.8 mmHg, body mass index averaged 27.9 and percentage body fat averaged 29%. The average reduction in BP of 11.4/9.8 mmHg (P = 0.0001) was accompanied by decreases in plasma renin activity of 1.82 ng/ml/h (P = 0.001) and in total plasma catecholamines of 77.9 pg/ml (P = 0.05). Percentage body fat decreased 1.3% (P = 0.02) and work capacity increased 1.2 METS (P = 0.002). There were no significant changes in body weight or plasma lipids, cortisol, insulin or urinary electrolyte excretion. Changes in SBP were correlated significantly with change in plasma renin activity (r = 0.38, P = 0.05). Favourable changes were also observed in mood (P = 0.04) and in one measure of type A behaviour (P = 0.04). None of the participants sustained an injury. We conclude that reduction of BP with endurance exercise training in these mildly hypertensive men was primarily associated with reduced plasma renin activity and did not adversely affect quality of life.