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The influence of T-cadherin on the pigmentation and proliferation of mouse melanoma B16F10 cells in vitro and on the growth and neovascularization of tumor cell masses formed by the B16F10 cells in a model of the chorioallantoic membrane of a chicken embryo is studied. It is found that the proliferative activity of the cells decreases in the cell culture of mouse melanoma upon the overexpression of T-cadherin in comparison with the cells in the control. It is shown in experiments in vitro that the B16F10 cells with the overexpression of T-cadherin are rarely settling are to the chorioallantoic membrane than the control cells. In addition, it is found that the control cells of mouse melanoma form tumors with area more 0.1 mm2 more often than the cells with the overexpression of T-cadherin and the amount of the vessels growing to tumor cell masses formed by the cells with the overexpression of T-cadherin is significantly lower than the same index for the cells in the control. Thus, the overexpression of T-cadherin in the B16F10 cells suppresses the proliferation of these cells in vitro and the growth of the tumor masses formed by melanoma cells on the chorioallantoic membrane and their neovascularization in vivo.

Progenitor stromal cells derived from adipose tissue (ADSC) and bone marrow (BMDSC) hold great promise for use in the cell-based therapy of ischemic diseases. It was demonstrated that these cells secrete a number of angiogenic cytokines that stimulate vascularization. It was demonstrated that ADSC or BMDSC injected intramuscularly or intravenously into the animals with experimental hind-limb ischemia improve vascularization. However, low oxygen levels and inflammation may impair the viability and functional activity of transplanted cells. We have examined ADSC and BMDSC properties in vitro under hypoxic and inflammatory conditions. ADSC and BMDSC derived from Balb/c mice have been cultivated under hypoxia or in the presence of inflammatory cytokines. The viability of cells assessed by annexin V-PE binding and 7AAD storage, as well as by the quantitative TUNEL method, was not changed under hypoxic conditions Cell exposure to inflammatory cytokines induced apoptosis in 70% of cells. Inflammatory cytokines did not stimulate gene expression of angiogenic growth factors. Under hypoxia conditions up-regulation of genes for pro-angiogenic factors and down-regulation of anti-angiogenic genes were more apparent in ADSC. Using angiogenesis models in vitro and in vivo, we demonstrated that stromal cell maintenance under hypoxic conditions increased their ability to stimulate the growth of blood vessels.

Aim. Circulating precursors of endothelial cells (PEC) play an important role in regeneration of damaged vascular endothelium and myocardium and neovascularization of ischemic tissues. The aim of this work was to study effect of disturbed carbohydrate metabolism (DCM) on the number of PEC in patients with different forms of CHD. Materials and methods. The number of PEC was determined by flow cytofluometry, insulin and C-peptide levels by IFA in 78 patients aged 40-69 (mean 55.5?0.9) years. Control groups comprised 17 subjects without CHD and DCM, 33 patients were allocated to the stable angina (SA) group (48% with DCM), 28 suffered acute coronary syndrome without segment ST elevation (ACS-ST) (39% had DCM). Results. The number of PEC was reduced in all CHD patients, by 23% in the SA group (p Conclusion. The number of PEC in peripheral blood of patients with CHD is reduced; the decrease is especially pronounced in patients with ACS-ST. SA is associated with the most significant decrease in circulating CD34+ cells in the presence of DCM whereas DCM has no marked effect on the number of PEC in ACS-ST patients. The higher the blood glucose level the smaller the number of circulating CD34+ cells.

Perivascular application of urokinase to ballooned artery stimulating the formation of neointima and constrictive arterial remodeling increased the content and activity of matrix metalloproteinases 2 and 9 in vivo. Application of recombinant tissue plasminogen produced no such changes. It was demonstrated that urokinase stimulates expression of matrix metalloproteinases in vivo.

Urokinase expression in the adventitia of rat common carotid artery increased on the 4th day after periadventitial damage. Periadventitial application of recombinant urokinase increased the area of the adventitia and the content of contractile and proliferating cells, while proteolytically inactive recombinant urokinase was ineffective.

The urokinase-type plasminogen activator, or urokinase, stimulates proliferation, adhesion, and migration of different type cells both due to its proteolytic activity and by activation of intracellular transduction pathways after interaction with the external cell surface. It is suggested that activation of p42/p44erk1,2 MAP-kinases in response to specific receptor binding to the urokinase N-terminal domain is the key event in initiation of cell migration. However, we have found that the central kringle-domain of urokinase has its own target on the cell surface, and that its binding causes a migration response of human smooth muscle cells (SMCs). In the present study, we have shown that the urokinase kringle-domain is required to activate the p38 MAP kinase cascade, and that its inhibition leads to suppression of the migration response of SMCs. On the contrary, stimulation of the p42/p44erk1,2 MAP-kinase cascade is determined only by proteolytic activity of urokinase and does not depend on its binding to SMCs. Selective inhibition of the p42/p44erk1,2 MAP-kinase cascade produced a depression of the SMC migration induced by catalytically active urokinase, but did not affect the migration induced by non-active urokinase. It is concluded that binding of the urokinase kringle-domain to a yet unidentified target at the SMC surface is required for activation of the p38 MAP-kinase cascade and of the cell migration. Urokinase was shown to stimulate phosphorylation and activation of regulatory light myosin chains that are required to increase the cytoskeleton dynamics and SMC motility. The participation of p42/p44erk1,2 and p38 MAP-kinase cascade in the realization of this effect is discussed.

In the last years stem cells (SC) have been identified in rodent and human hearts. These cells have ability to multilineage differentiation in vitro and in vivo and improve cardiac function. The development of new methods of isolation SC offers new approaches to cardiac regeneration. However, the question of how individual patient characteristics influence the number of SC remains unclear. In our study we aimed to define the correlation between patient characteristics and SC number. Our findings suggest that clinical characteristics and severity of the disease may affect the yield of SC in heart tissue. Our data contribute to the development of efficient methods for SC isolation for stem cell therapy.

Urokinase-type plasminogen activator (uPA) is a serine protease that converts the plasminogen zymogen into the enzymatically active plasmin. uPA is synthesized and secreted as the single-chain molecule (scuPA) composed of an N-terminal domain (GFD) and kringle (KD) and C-terminal proteolytic (PD) domains. Earlier, the structure of ATF (which consists of GFD and KD) was solved by NMR (A. P. Hansen et al. (1994) Biochemistry, 33, 4847-4864) and by X-ray crystallography alone and in a complex with the soluble form of the urokinase receptor (uPAR, CD87) lacking GPI (C. Barinka et al. (2006) J. Mol. Biol., 363, 482-495). According to these data, GFD contains two β-sheet regions oriented perpendicularly to each other. The area in the GFD responsible for binding to uPAR is localized in the flexible Ω-loop, which consists of seven amino acid residues connecting two strings of antiparallel β-sheet. It was shown by site-directed mutagenesis that shortening of the Ω-loop length by one amino acid residue leads to the inability of GFD to bind to uPAR (V. Magdolen et al. (1996) Eur. J. Biochem., 237, 743-751). Here we show that, in contrast to the above-mentioned studies, we found no sign of the β-sheet regions in GFD in our uPA preparations either free or in a complex with uPAR. The GFD seems to be a rather flexible and unstructured domain, demonstrating in spite of its apparent flexibility highly specific interaction with uPAR both in vitro and in cell culture experiments. Circular dichroism, tryptophan fluorescence during thermal denaturation of the protein, and heteronuclear NMR spectroscopy of ¹⁵N/¹³C-labeled ATF both free and in complex with urokinase receptor were used to judge the secondary structure of GFD of uPA.

Collateral blood flow is a natural way of compensation of blood supply of ischemic myocardium however its efficacy is highly individual. Revelation of potentially modifiable factors acting on which it would be possible to change the state of collateral blood flow will allow to find an approach to improvement of prognosis and quality of life of patients with ischemic heart disease. In this review we show significance of collateral blood flow, analyze mechanisms of its formation, and stress the role of vascular endothelial growth factor-A (VEGF-A) and its genetic polymorphism.

This report contains authors own data about hyperglycemia impact on main functional properties of endothelial cells, mesenchymal stem cells and circulating progenitor cells, which define their participation in angiogenesis. Obtained data shows that cultivation of endothelial cells in hyperglycemic conditions leads to decrease of their ability for targeted migration and vascular-like structures formation on matrigel, and to suppression of VEGF receptors expression in these cells. Mesenchymal stem cells cultivated in hyperglycemic conditions have altered expression profile, decreased ability to stimulate angiogenesis via paracrine activity. Hyperglycemia in CHD patients with concomitant diabetes mellitus type II most probably lead to circulating bone marrow progenitor cells mobilisation distortion in response to tissue ischemia and damage to the endothelium, that can infringe upon their participation in endothelium reparation and angio- and vasculogenesis in the ischemic conditions. Found distortions can be used as targets for the treatment aimed at cardiovascular complications prevention in diabetic patients.

In cultured fibroblasts, urokinase stimulated expression of MMP-9 and generation of ROS, while antioxidant ebselen abolished the stimulating effect of urokinase on MMP-9 expression. sTNF-α produced similar and more pronounced stimulating effect. The data showed that urokinase could regulate MMP-9 expression via ROS generation in fibroblasts, which can play an important role in stimulation of their migration and development of constrictor (negative) vascular remodeling due to thickening of the adventitia.

The search for sources of stem/progenitor cells the use of which has a potential to affect course of ischemic heart disease and chronic heart failure is conducted nowadays in many countries. Resident cardiac stem cells (CSC) were revealed during recent years on the basis of expression of c-kit, sca-1, MDR1, and islet-1 markers. In vitro experiments demonstrated possibility of their differentiation into cardiomyocytes, smooth muscle cell and endothelial cells. Introduction of CSC in injured myocardium in animals facilitated its partial repair and short term improvement of cardiac function. This holds promise for the use of these cells in the future. In the review we have attempted to summarize literature data on resident CSC and their application for the treatment of heart diseases.

In the past few years it has been established that the heart contains a reservoir of stem and progenitor cells that have the ability to differentiate in vitro and in vivo toward vascular and cardiac lineages and that show cardiac regeneration potential in vivo following injection into the infracted myocardium. The aim of the present study was to characterize cardiac stem cells in the tissue of chronic left ventricular aneurism. It was shown that human c-kit positive cells were scattered in fibrous, muscle and adipose parts of aneurism tissue. C-kit positive cells localized mainly in fibrous tissue nearby large vessels, however, c-kit positive cells did not express endothelial, smooth muscle or cardiomyocyte cell markers. Co-localization experiments demonstrated that all c-kit positive cells were of non-hematopoietic origin, since they did not express markers such as CD34 and CD45. Majority of c-kit positive cells expressed MDR1, but showed no proliferation activity (Ki67). It thus appears that aneurism tissue could be an alternative source of autologous cardiac stem cells. However, their regeneration capacity should be further explored.

Stromal cells from subcutaneous adipose tissue (adipose derived stromal cells - ASCs) are perspective for cell therapy of ischemic states because of ability to stimulate growth of vessels. For the elucidation of mechanisms of angiogenic action of ASCs we used the model of co-cultivation of ASCs with cells isolated from postnatal hearts (fraction of cardiomyocutes - CMC). CMC fraction contained mature cardiomyocytes, endothelial and progenitor cells. On the 2-nd day spontaneously beating colonies of CMC with growing from them CD31-positive capillary-like structures were formed in CMC culture. Observed structures were unstable and came apart after 5 days of cultivation. At co-cultivation of CMC with ASCs formation of stable ramified CD31-positive structures was observed. Using the method of co-cultivation of CMC with mitomycin C treated ASCs and the method of immune magnetic depletion for removal of epithelial cells from the CMC fraction we found that ASCs stimulates formation of capillary like structure at the account of secretion of angiogenic factors, stabilization of forming CD31-positive structures at the account of intercellular contacts and stimulation of endothelial differentiation of progenitor cells present in CMC fraction.

Endothelial progenitor cells (EOCs) play a key role in reendothelization of injured blood vessels and in endogenous neovascularization of ischemic tissues. In the presented article, the mechanisms of endothelial function impairment and the role of EPCs in their correction are discussed. The objective of our study was to investigate the number of CD34+ cells in patients with different forms of ischemic heart disease (IHD) and association of this parameter with endothelial dysfunction. We quantified the numbers of CD34+ cells by flow cytometry, measured the brachial artery flow-mediated vasodilatation (FMD) and the common carotid artery intima-media thickness (IMT) by ultrasonography in 28 patients with ST-segment elevation acute coronary syndromes (ACS), in 33 patients with stable angina (SA) and in 17 subjects without IHD (control group). The level of CD34+ cells was lower in both groups of IHD, especially in patientes with ACS, and was associated with endothelial dysfunction. We suppose that CD34+ cells contribute to reparation of injured endothelium and the reduction of their numbers in peripheral blood indicates endothelial state.

Poor content of oxygen indices gene expression for angiogenic growth factors both in adipocytes and in stromal cells of the fatty tissue. Stimulation of blood vessels by these factors leads to hyperplasia ofpregenitior cells and by their differentiation. This review mentions functional changes occurring in the fatty tissue cells under the effect of hypoxy.

Endothelial dysfunction and cell loss lead to atherosclerosis and its outcomes. Several recent studies suggested that endothelial progenitor cells (EPCs) play a key role in reendothelialization of injured vessels and in endogenous neovascularization of ischemic tissues. Modulation of EPCs number and functional activity or EPCs transplantation are a promising outlook for treatment of cardiovascular disease. In the present review, assessment of endothelial function, mechanisms of its impairment and role of EPCs in their correction are elucidated.

To measure and compare the level of circulating precursors of endothelial cells in patients with acute coronary non-ST-elevation syndrome (NSTES), patients with stable effort angina (SEA) before coronary stenting and after it and persons with documented absence of coronary heart disease (CHD).The trial included 19 patients with acute coronary NSTES, 20 patients with SEA and 14 patients free of CHD. Blood samples were stained with antibodies CD45-FITC (Becton Dickinson), CD34-PerCP (Becton Dickinson), KDR-PE (RD systems). Count of cell populations was measured with flow cytofluorimetry (FACSCalibur (Becton Dickinson).SEA patients had the number of circulating cells CD34+ including hematopoietic cells and endothelial precursors (EP) two times lower versus that in the controls (0.650 +/- 0.086 and 1.216 +/- 0.242%, respectively, p = 0.037). No significant differences were found by the number of CD34+KDR+ cells between the groups. A trend was found to lower number of CD34-KDR+ cells in EA patients compared to control. The differences reached significance on day 1 and 3-5 after endovascular interventions (0.067 +/- 0.022, 0.060 +/- 0.017 and 0.188 +/- 0.052%, respectively, p = 0.024 and p = 0.021).The count of blood CD34+ cells in combination with other indicators can be used as an additional factor confirming the presence of chronic myocardial ischemia.

Two inexpensive inhibitors non-toxic to B. subtilis cells, O,O-diethyl-1-(N-α-hydrohexafluoro-isobutyryl)amino-1-methyl-propylphosphonate and O,O-diisobutyl-1-[2-(ethoxycarbonyl)amino-perfluoroprop-2-yl]-1-methylpropylphosphonate, when added to the culture broth, are able to prevent the proteolytic degradation of recombinant human proinsulin, secreted byB. subtilis AJ73apr73 npr− cells.

Expression of urokinase receptors on peripheral human monocytes from healthy donors and patients with angina pectoris is studied by125I-prourokinase receptor binding assay and flow cytofluorimetry with monoclonal antibodies to the urokinase receptor. Plasma concentration of urokinase is measured by ELISA. It is shown that in patients with angina pectoris plasma content of urokinase is higher by 30%, while the number of free urokinase receptors on monocytes is half lower than that in healthy donors.

Results of studies of properties of adipose tissue stromal cells are summarized in this review. It contains data on separation and cultivation of these cells as well as description of their antigenic characteristics, ability to differentiate into cells of mesenchymal and nonmesenchymal origin, angiogenic potential, and potential for transfection and transfer of therapeutic genes. Analysis of perspectives of clinical use of adipose tissue stromal cells in therapy of cardiovascular and other diseases is also presented.

One of most widely spread causes of hypertrophic cardiomyopathy (HCMP) is mutation in cardiac beta-myosin heavy chain gene. Data on contribution of this mutation to development of HCMP in Russian patients are very limited. We conducted screening of beta-myosin heavy chain gene for the presence of mutations in 116 patients with confirmed HCMP (probands). DHPLC was used with subsequent sequencing of DNA fragments. Genetic defects of beta-myosin heavy chain were found more than in every 10-th patient. These defects were represented by 13 mutations (Ala729Pro mutation was found twice). Phenotypes of majority of known mutations in Russian population did not differ substantially from their phenotypes in other populations. Six mutations had not been previously described; most of them were associated with especially severe clinical and hemodynamic signs and relatively unfavorable course of the disease. Thus beta-myosin heavy chain gene mutation play important role in etiology of HCMP in patients in Russia.

The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.

T-cadherin is an unusual glycosilphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. In contrast to classical cadherins, tissue distribution of T-cadherin so far remained unknown. We examined tissue distribution of T-cadherin in rats using Western blotting and immunohistochemical method. Our results show that T-cadherin is expressed in all types of muscles (cardiac, striated, and smooth muscles), in brain neurons, and spinal cord, in the vessel endothelium, at the apical pole of intestinal villar epithelium, in the basal layer of skin, and eosophagal epithelium. Blood-derived and lymphoid cells as well as connective tissue were T-cadherin-negative. The highest level of T-cadherin expression was revealed in the cardiovascular system. Although T-cadherin was detected in smooth muscle cells, its role in the intimal thickening and restenosis is not known. We examined T-cadherin expression within 1-28 days after balloon injury of rat left carotid arteries. T-cadherin expression was valued immunohistochemically with semiquantitative method. In uninjured arteries, T-cadherin was expressed in endothelial (vWF-positive) cells, and smooth muscle (alpha-actin-positive) cells (SMCs). After denudation of arterial wall, T-cadherin was present both in the media and neointima. We revealed dynamics of T-cadherin expression in the media of injured artery: an essential increase being registered at the stage of cell migration and proliferation in the media and neointima (1-7 days), followed by its decrease to the baseline level (10-28 days). The high upregulation of T-cadherin expression in the media and neointima during migration and proliferation of vascular cells after vessel injury enables us to suggest the involvement of T-cadherin in vessel remodeling after balloon catheter injury.

Analysis of relationships between clinical characteristics of the patients, high concentration of acute phase proteins--fibrinogen, C-reactive protein (CRP), activity of the inhibitor of type 1 plasminogen activator (PAI-1)--and frequency of angina recurrence after successful coronary angioplasty (CA).The trial included 53 patients after successful CA for a single hemodynamically significant stenosis. Peripheral blood was examined for plasm fibrinogen, CRP, activity of PAI-1 one day before and 2 days, 3 and 6 months after CA. After 12-month follow-up the patients were divided into two groups: angina-free patients (n = 37) and with recurrent angina (n = 16).Significant differences between the above groups were in PAI-1 activity 3 and 6 months after CA, in CRP initially, on day 2, after 6 months after CA (p0.05) but multifactor analysis has found that only CRP level both initial and on day 2 after CA is an independent predictor of recurrent angina pectoris after successful CA.An anginal recurrence after successful CA can be predicted by the initial and postoperative day 2 levels of CRP.

Periadventitial application of the urokinase-plasminogen activator (uPA) in pluronic gel to an injured artery stimulated the neointima and neoadventitia formation as well as cell migration and proliferation in vivo. In contrast, the tissue-type plasminogen activator (tPA) reduced the number of neointimal smooth muscle cells and neointimal area and attenuated the lumen stenosis after a balloon catheter injury of the rat carotid artery. This ability to stimulate the neointima and neoadbentitia formation was found to be quite specific for the uPA. The findings suggest that this uPA property provides a specific functional target for attenuating growth of the damage.

The therapeutic potential of gene therapy in cardiovascular disease such as post-angioplasty restenosis, myocardial ischaemia and severe peripheral artery disease ischemia are considered.

Using the immunohistochemistry and a standard reverse transcriptase-polymerase chain reaction assay optimized to estimate the mRNA levels, we observed a 2-fold increased uPA expression by the SMCs in injured vessels as compared with uninjured vessels. The uPA elevation occurred within 6 hours from the injury and persisted for 96 hours after the injury. The uPAR expression was also elevated after an injury although it occurred slower and more gradually. The data obtained suggest that the uPA is capable of contributing to both the SMC migration, replication and accumulation in the neointima early after balloon catheter injury of the carotid artery in rats.

Obsidan (propranolol) monotherapy was investigated for the effect on the density of lymphocytic beta2-adrenoreceptors (B max), the activity of lymphocytic homogenates adenylate cyclase (AC), plasma renin activity (PRA), aldosterone concentration (A) and plasma catecholamines (CA). Obsidan treatment brought about a 40% increase in B max without a significant changes in AC activity. Contrary to a significant fall in PRA, A and norepinephrine in plasma reduced insignificantly. Changes in B max correlated with its baseline level (r = -0.56, p0.01), PRA (r = 0.57, p0.01) and A level in plasma (r = 0.62, p0.01). No significant correlations appeared between hypotensive effect of the drug and drug-related changes in B max and AC activity, while PRA and A concentrations showed such dependence. B max and before treatment mass of the left ventricular myocardium correlated significantly (r = = 0.595, p0.01). A small decrease in the myocardial mass followed obsidan administration, being related to B max (r = = 0.497, p0.05). It is concluded that obsidan-induced changes in lymphocytic beta 2-adrenoreceptors correlate with alterations in the activity of renin-angiotensin-aldosterone system and myocardial hypertrophy dynamics.

Separated were surface antigens' complex preparations from the native biomass of Candida yeast-like fungi, by using the beta-mercaptoethanol-induced undestructive extraction technique. The preparations were analysed by the highly effective liquid chromatography technique, double immunodiffusion in agar, immunoelectrophoresis, and in experiments on intradermal titration on intact and sensibilized guinea-pigs. It was indicated that the complex preparations of surface antigens extracted from C. maltosa, C. valida and C. scotti were characterized by low reactogenicity and high precision in experimental intracutaneous allergotesting on guinea-pigs. The immunochemical and allergenous activity was higher in preparations with molecular masses of 600 kD. These complex preparations can be used as allergens in the hygienic forming of fodder protein producent strains.

This paper determines the density of beta-adrenoreceptors of intact lymphocytes from patients with stable essential hypertension and compares it with that of normal subjects. Specific binding of tritium-dihydroalprenolol with intact lymphoctes under certain described conditions was characterized by saturation and high affinity. The results are evidence of a statistically significant increase (by 42%) in beta-adrenoreceptor density of intact lymphocytes in essential hypertension.

The characteristics of lymphocyte ..beta../sub 2/-adrenoreceptors in patients with essential hypertension were studied in this paper after a short course of propranolol monotherapy. The density of ..beta../sub 2/-adrenoreceptors on intact lymphocytes was determined in three patients with the use of /sup 3/H-dihydroalprenolol, in the rest with /sup 125/I-cyanopindolol. Specific binding of /sup 125/I-CIP with intact cells, like that of /sup 3/H-DHA, was characterized by high affinity and saturation.

Correlations between sympathoadrenal, renin-angiotensin and cardiovascular (BP and heart rate) response to psychoemotional and physical stress and antebrachial skin vascular response to noradrenaline were examined in patients with essential hypertension. Four groups of patients were identified on the basis of the magnitude of variation in the examined parameters. The progress of the disease over the past two years was assessed in all patients. The prognosis was particularly unfavorable in the "hyperreactive" group which showed a set of distinctive features: increased vascular response to noradrenaline, a greater BP rise in response to stress, greater sympathoadrenal activation, increased neuroticism, as well as significantly older age of the patients and greater severity and duration of the disease. No intergroup differences in plasma renin activity could be demonstrated. Possible use of vascular response to noradrenaline, and BP and plasma catecholamine variation in response to psychoemotional stress as criteria for the assessment of the severity and outcome of essential hypertension is discussed.

Lymphocytes beta 2-receptor density (LBRD) was studied by binding with 125ICYP in 18 male patients with mild/moderate essential hypertension (EH) before and after propranolol monotherapy. In 5 of these patients LBRD was determined before and after dynamic exercise also. Propranolol therapy evoked different changes in LBRD in patients with EH. According to these results, all the patients were divided into 2 groups: the patients who respond to propranolol administration by an increase in the LBRD were attributed to the 1 group. If the LBRD decreased after propranolol, the patients were attributed to the 2 group. Propranolol had pronounced hypotensive effect in the 2 group and no hypotensive effect in the 1 group. Heart rate was significantly higher initially and decreased significantly more after treatment in the 2 group. In this group initial values of LBRD were significantly higher than in the 1 group. Exercise produced different changes in LBRD, which correlated with the changes produced by propranolol treatment. The positive correlations were found between LBRD and left ventricular myocardial mass and interventricular septum thickness. The data obtained indicate that LBRD is regulated in a qualitatively different manner in the two groups of patients with EH which appears to be related to baseline renin or perhaps catecholamine levels.

Captopril effects were studied in 27 patients with second-stage essential hypertension following administration of a single 25 mg oral dose of the drug. Blood pressure (BP), blood angiotensin-1-converting enzyme (ACE) activity, active (APR) and inactive (IPR) plasma renin levels were measured every 30 minutes for 3 hours. Before and near the end of the acute test, urinary kallikrein and catecholamine excretions were measured, and systemic and regional hemodynamic changes assessed. BP decreased in 21 patients: 11 of those had low basal APR (group 1), and 10 had normal or moderately elevated APR (group 2). The greatest hypotensive effect was observed within 1.5 hours after the administration, coinciding with the most marked ACE inhibition. There was no significant intergroup difference with respect to the extent of the hypotensive effect. No correlation was found between the hypotensive effect and the degree of ACE inhibition. All patients showed significantly decreased arteriolar tone, increased venous distensibility, decreased total peripheral resistance, and expanded end diastolic volume, while their cardiac output and heart rate remained unaffected. Hypertensive patients with low APR gave no evidence of renin-angiotensin inhibition or kallikrein-kinin activation that might have accounted for the hemodynamic effect of captopril.

Two forms of Ca(++)-activated protease (calpain I and calpain II) associated with an endogenous inhibitor (calpastatin) were detected in a cytosolic fraction of the olfactory tissue of vertebrates (pig, rat). Using ion exchange chromatography on DEAE-cellulose column, calpain I is divided into 2 peaks (eluting by 0.07-0.15 and 0.22-0.25 M NaCl), and calpain II is eluted by 0.35-0.40 M NaCl. The calpain activity was detected in fractions eluted by 0.1-0.17 M NaCl. The Ca(++)-activated protease was demonstrated also in a fraction of cytoskeleton of olfactory tissue insoluble in a 1% solution of Triton X-100. The activity can be detected by Ca(++)-dependent destruction of exogenous substrate (casein), and by Ca(++)-dependent degradation of cytoskeletal endogenous proteins (16, 18 and 20 kDa), of which one may be calmodulin.