Induction of Vasculo- and Osteogenesis in Spheroids Formed by Adipose-Derived Stromal Cells.

Vascularization of bioengineered bone tissue constructs remains a challenging problem of regenerative medicine. Spheroids generated in 3D culture of adipose-derived stromal cells supplemented with inducing factors demonstrate stable characteristics and express of mesenchymal, endothelial, and osteoblasts markers, and represent a prototype of vascularized microtissue. Adipose-derived stromal cells spheroids induced to both angio- and osteogenic differentiation can be used in development of new innovative technologies for in vitro fabrication of vascularized bioequivalents for repair of large bone defects.

The technology of obtaining multipotent spheroids from limbal mesenchymal stromal cells for reparation of injured eye tissues.

It is known that stem and progenitor cells open new possibilities for restoring injured eye tissues. Limbal eye zone, formed mainly by derivatives of neural crest, is the main source of stem cells for regeneration. The current study considers development of innovative technology for obtaining 3D spheroids from L-MMSC. It was shown that under 3D conditions L-MMSC due to compactization and mesenchymal-epithelial transition self-organize into cellular reparative modules. Formed L-MMSC spheroids retain and promote undifferentiated population of stem and progenitor limbal cells, as supported by expression of pluripotency markers - Oct4, Sox2, Nanog. Extracellular matrix synthetized by cells in spheroids allows retaining the functional potential of L-MMSC that are involved in regeneration of both anterior and, probably, posterior eye segment.

[A rare case of oxalate nephropathy with acute renal injury].

Objective: This case demonstrates the difficulty of diagnostics of oxalate nephropathy and possibility of development of acute kidney injury. Summary: The paper describes a patient with oxalate nephropathy and acute kidney injury. Specific features of oxalate diathesis are discussed as well as approaches to its diagnosis. Clinical peculiarities and diagnostic difficulties are described. Conclusions: Early diagnosis of oxalate nephropathy and treatment permits to improve prognosis.

Protein transfection of intact microvessels specifically modulates vasoreactivity and permeability.

Precise regulation of microvascular tone and barrier function is essential for proper coronary perfusion and performance. Agonist-induced alterations in either or both of these functions ultimately lead to microcirculatory dysfunction and cardiac insufficiency. Two important pathways involved in regulating vasomotor response and barrier function are the activation of nitric oxide synthase (NOS) and upregulation of protein kinase C (PKC). To date, studies of these two signaling proteins have relied mainly on pharmacological approaches. Unfortunately, the specificity of various inhibitors can be cause for concern. In order to address this problem, a protein transfection technique we developed for cultured endothelial cells has been modified and applied to isolated, intact coronary microvessels. Our results from green fluorescent protein transfection in arterioles and venules showed that this procedure could be used to introduce proteins into the microvascular wall. By transfecting inhibitor peptides against NOS and PKC into coronary arterioles and venules, we have been able to determine the specific roles of these two enzymes in vasodilation and hyperpermeability responses.

Oxidative stress impairs cardiac chemoreflexes in diabetic rats.

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sham- and STZ-treated rats were chronically treated with an antioxidant, vitamin E (60 mg/kg per os daily, started 2 days before STZ). Animals were studied 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympathetic afferent activities in response to stimulation of chemosensitive sensory nerves in the heart by epicardial application of capsaicin (Caps) and bradykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 microg) evoked a vagal afferent mediated reflex depression of RSNA and MABP, which was significantly blunted in STZ-treated rats (P < 0.05). In vagal-denervated rats, Caps and BK (1-10.0 microg) evoked a sympathetic afferent-mediated reflex elevation of RSNA and MABP, which also was significantly blunted in STZ-treated rats (P < 0.05). Chronic vitamin E treatment effectively prevented these cardiac chemoreflex defects in STZ-treated rats without altering resting blood glucose or hemodynamics. STZ-treated rats with insulin replacement did not exhibit impaired cardiac chemoreflexes. In afferent studies, Caps and BK (0.1 g-10.0 microg) increased cardiac vagal and sympathetic afferent nerve activity in a dose-dependent manner in sham-treated rats. These responses were significantly blunted in STZ-treated rats. Vitamin E prevented the impairment of afferent discharge to chemical stimulation in STZ rats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac chemosensitive nerve endings, and these disturbances can be prevented by chronic treatment with vitamin E. These results suggest that oxidative stress plays an important role in the neuropathy of this autonomic reflex in diabetes.

Protein kinase C activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes.

The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information regarding the barrier function of coronary exchange vessels in the disease state. The aim of the present study was to evaluate the permeability property of coronary microvessels during the early development of experimental diabetes with a focus on the protein kinase C (PKC)-dependent signaling mechanism. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused porcine coronary venules. The administration of high concentrations of D-glucose induced a dose-dependent increase in the Pa value, which was prevented by blockage of PKC with its selective inhibitors bisindolylmaleimide and Goe 6976. More importantly, an elevated basal permeability to albumin was observed in coronary venules at the early onset of streptozotocin-induced diabetes. The hyperpermeability was corrected with bisindolylmaleimide and the selective PKCbeta inhibitor hispidin. Concomitantly, protein kinase assay showed a high PKC activity in isolated diabetic venules. Immunoblot analysis of the diabetic heart revealed a significant subcellular translocation of PKCbetaII and PKCepsilon from the cytosol to the membrane, indicating that the specific activity of these isoforms was preferentially elevated. The results suggest that endothelial barrier dysfunction attributed to the activation of PKC occurs at the coronary exchange vessels in early diabetes.

Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings.

OBJECTIVE: The effects of capsaicin on sensory neurons are mediated by its interaction with a specific membrane receptor and opening of a non-selective cation channel. In the rat heart, capsaicin-sensitive nerve endings are known to be activated by oxygen radicals. We investigated the possibility that free oxygen radicals stimulate sensory nerve endings by acting upon the capsaicin receptor. METHODS: We studied the effects of capsaicin (0.16-16.0 nmol), bradykinin (0.1-10 nmol), H2O2 (1.5-30 mumol), and xanthine + xanthine oxidase (X + XO, 1 mumol + 0.03 mU) applied to the surface of the rat heart for 30 s on the activity of cardiac, capsaicin-sensitive, vagal and sympathetic afferent fibers before and after blockade of capsaicin receptors with capsazepine (200 micrograms/kg, i.v.), a specific antagonist for the capsaicin receptor. RESULTS: Application of capsaicin (0.32-16.0 nmol), H2O2 (9-30 mumol), bradykinin (1-10 nmol), and X + XO increased cardiac vagal and sympathetic afferent activity. Administration of capsazepine had no effect on the baseline activity of either vagal or sympathetic cardiac afferents, but it abolished the response of the afferent fibers to all doses of capsaicin, H2O2, and X + XO tested. Capsazepine had no effect on afferent activation by bradykinin. Administration of another capsaicin receptor blocker, ruthenium red (780 micrograms/kg, i.v.), had similar effects. CONCLUSIONS: The results of these experiments indicate that blockade of capsaicin receptors inhibits activation of vagal and sympathetic cardiac afferent fibers by free oxygen radicals. The fact that capsazepine and ruthenium red did not affect the afferent response to bradykinin suggests that this effect of the blockers was specific for capsaicin receptors. The possible functional implications of this interaction are discussed.

Lysophosphatidic acid enhances contractility of isolated airway smooth muscle.

The effects of the simple phospholipid mediator lysophosphatidic acid (LPA) on the contractile responsiveness of isolated tracheal rings from rabbits and cats were assessed. In both species, LPA increased the contractile response to the muscarinic agonist methacholine, but LPA did not induce contraction on its own. Conversely, LPA decreased the relaxation response to the beta-adrenergic-agonist isoproterenol in both species. Concentrations of LPA as low as 10(-8) M were effective, and the effects of LPA were rapidly reversed on washing. Phosphatidic acid was much less effective, requiring higher concentrations and producing only a minimal effect. Contractions induced by serotonin and by substance P also were enhanced by LPA, but KCl-induced contractions were unaffected. LPA inhibited the isoproterenol-induced relaxation of KCl-precontracted rings, similar to its effects on methacholine-precontracted rings, and relaxation induced by the direct adenylyl cyclase activator forskolin was inhibited in a manner similar to that induced by isoproterenol. Epithelium removal did not alter the contraction-enhancing effect of LPA. The ability of LPA to both enhance contraction and inhibit relaxation of airway smooth muscle suggests that LPA could contribute to airway hypercontractility in asthma, airway inflammation, or other types of lung injury.

Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in heart failure.

There is good evidence that the cardiopulmonary and arterial baroreflexes are blunted in chronic heart failure (HF). Other evidence, however, suggests that the cardiac chemoreflex is enhanced during HF. In the present study, we sought to determine whether HF alters the sensitivity of cardiac vagal chemosensitive endings to bradykinin (BK), an endogenous mediator that activates ventricular C fiber afferents. We measured the activity of cardiac vagal single fibers and compared the afferent responses to left atrial injections of BK and capsaicin in sham-operated and pacing-induced HF dogs. The capsaicin-sensitive endings did not respond to changes in cardiac pressures evoked by vascular snares and were C fiber endings (0.8-2.1 m/s). Most were located in the left heart. There was no difference in rate or pattern of resting discharge of the cardiac vagal fibers between HF and sham groups (1.5 +/- 0.5 vs. 1.3 +/- 0.3 impulses/s, respectively). The afferent response to BK (0.001-1 microgram/kg), but not capsaicin (1-10 micrograms/kg), was greater in HF compared with sham dogs. Captopril (2 mg/kg i.v.) significantly enhanced resting discharge (P < 0.05) from cardiac chemosensitive vagal afferents in HF but not sham dogs. The afferent response to BK in both groups was significantly (P < 0.05) and similarly enhanced. Indomethacin (5 mg/kg i.v.) significantly inhibited resting discharge (P < 0.05) and nearly abolished the afferent responses to lower doses of BK in HF, but did not affect resting discharge and less effectively attenuated responses to BK in sham dogs. Responses to capsaicin did not differ between HF and sham animals. From these results, we conclude that 1) resting discharge from cardiac vagal chemosensitive endings is not altered in HF, 2) these vagal endings exhibit an enhanced sensitivity to exogenous BK but not to capsaicin in the HF state, 3) angiotensin-converting enzyme activity inhibits resting discharge from these afferents in HF, and 4) the cyclooxygenase system contributes to the enhanced BK responsiveness of cardiac chemosensitive endings in HF.

Pulmonary C-fiber activation before and after peptidase inhibition in rats.

Inhibition of peptidases within the lungs not only potentiates the effects of neuropeptides released from C-fibers but also the effects of bradykinin and capsaicin both of which stimulate C-fibers. To determine if peptidase inhibition potentiates C-fiber activation, we challenged pulmonary C-fibers in rats with capsaicin or bradykinin before and after inhibition of neutral endopeptidase (NEP) or angiotensin converting enzyme (ACE). Inhibition of NEP by phosphoramidon (10 mg/kg, i.v.) potentiated the effect of capsaicin (0.5-1 micrograms, i.v.) on C-fiber activity but did not change the response to bradykinin (1-2 micrograms, i.v.). Inhibition of ACE by captopril (5 mg/kg, i.v.) potentiated C-fiber activation by either bradykinin or capsaicin. Aerosol administration of either phosphoramidon (1 x 10(-5) M, 2 min) or captopril (4.6 x 10(-3) M, 2 min) potentiated C-fiber activation by capsaicin aerosol (1.6 x 10(-4) M, 1 min) but not by bradykinin aerosol (9.4 x 10(-5) M, 1 min). Therefore, inhibition of NEP or ACE may potentiate airway obstructive mechanisms initiated by C-fiber stimulation.

Renal sympathetic nerve activity during cardiac ischemia and reperfusion in rats.

We studied the role played by prostaglandins and oxygen-derived free radicals in mediating reflex changes in renal sympathetic nerve activity (RSNA) during myocardial ischemia and reperfusion. Ligation of the left coronary artery for 20 min and reperfusion for 10 min were performed in anesthetized rats with sinoaortic denervation and with intact cardiac afferent nerves (control, n = 7), with cardiac sympathetic denervation (SD, n = 6), with vagal denervation (VD, n = 7), and with combined SD + VD (n = 6). In control rats, RSNA decreased by 10 +/- 3% from baseline (P < 0.05) during the first minute of ischemia and increased above baseline after 5 min of ischemia, with the maximum increase at the first minute of reperfusion. In rats with SD, RSNA decreased by 19 +/- 4% from baseline (P < 0.05) at the first minute of ischemia and remained depressed during the entire ischemic and reperfusion periods. In rats with VD, RSNA increased by 26 +/- 5% from baseline (P < 0.05) at the first minute of ischemia, and the increase in RSNA at the end of the ischemic period and at reperfusion was greater than in control rats. No changes in RSNA during ischemia and reperfusion were observed with combined SD + VD. Reflex changes in RSNA that occurred at the onset of ischemia in both VD (n = 7) and SD (n = 7) rats were abolished by indomethacin (5 mg/kg i.v., 20 min before ischemia). Reflex changes in RSNA after prolonged ischemia (> 10 min) and during reperfusion in both VD (n = 7) and SD (n = 7) rats were abolished by the antioxidant deferoxamine (20 mg/kg i.v., 20 min before ischemia). Deferoxamine also diminished the increase of RSNA at the onset of ischemia in VD rats. Thus, in rats, the vagal afferent reflex predominates during early ischemia and the sympathetic afferent reflex predominates during prolonged ischemia and reperfusion. Reflex changes in RSNA that occur at the onset of ischemia are mediated by activation of vagal and sympathetic afferent endings by prostaglandins. Reflex changes in RSNA after prolonged ischemia and during reperfusion are mediated by activation of vagal and sympathetic afferent endings by oxygen-derived free radicals.

Cardiac vagal afferent stimulation by free radicals during ischaemia and reperfusion.

1. Myocardial ischaemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen free radicals, which are well known to be produced during ischaemia and reperfusion, contribute to this excitation. 2. Activity from vagal afferent fibres in rats, whose endings were located in the walls of all four chambers of the heart, was recorded in response to topical application of pro-oxidant chemicals to the surface of the heart. Activity was also recorded from vagal afferent fibres, whose endings were located in the left ventricle, in response to occlusion of the left anterior coronary artery (LAC) for 30 min and subsequent reperfusion. A majority of the recorded fibres were classified as chemosensitive C-fibre endings due to their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1-10 micrograms) to the surface of the heart encompassing the receptive field and their conduction velocities. 3. Topical application of either H2O2 or xanthine/xanthine oxidase to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. This effect was reproducible, dose-dependent and was not due to [H+]. 4. Administration of the superoxide radical scavenging enzyme, superoxide dismutase (20000 U/kg, i.v.), decreased the response of fibres to xanthine/xanthine oxidase but had no effect on the activation caused by H2O2. The antioxidants deferoxamine (20 mg/kg, i.v.) or dimethylthiourea (10 mg/kg, i.v.), which scavenge the hydroxyl radical, abolished the responses to xanthine/xanthine oxidase and H2O2. Administration of indomethacin (5 mg/kg, i.v.) had no effect on the afferent response to H2O2. 5. In response to ligation of the left anterior coronary (LAC), the activity of chemosensitive endings within the ischaemic zone increased within the first 2 min of occlusion. Endings outside the ischaemic zone were not affected at the beginning of ischaemia. Reperfusion activated only chemosensitive endings responsive to topical H2O2. These reperfusion-sensitive endings were located both within and outside the ischaemic zone of the left ventricle. 6. Indomethacin (5 mg/kg, i.v.) prevented activation of chemosensitive endings at the beginning of LAC occlusion regardless of their sensitivity to H2O2 but had no effect on the response to reperfusion. Conversely, deferoxamine (20 mg/kg, i.v.) had no effect on the activation of chemosensitive fibres at the onset of ischaemia, whereas it completely prevented activation at reperfusion. 7. We propose that there are two different mechanisms that activate chemosensitive afferent vagal fibres in the rat heart during ischaemia and reperfusion. The first causes excitation of these endings at the onset of ischaemia and is mediated by prostaglandin synthesis within the ischaemic zone. The second mechanism leads to a more widespread activation of chemosensitive afferents in the left ventricle during prolonged ischaemia and at the moment of reperfusion and is mediated by oxygen free radical formation.

Neuropeptide depletion impairs postischemic recovery of the isolated rat heart: role of substance P.

OBJECTIVES: Ischemia of the myocardium stimulates cardiac sensory nerve endings resulting in the local release of neuropeptides. The significance of the release of neuropeptides, such as substance P (SP), for the function of the heart during ischemia and reperfusion is not known. We examined the effects of both chronic and acute neuropeptide depletion and of SP administration on contractile function and rhythmicity of the isolated rat heart during global ischemia and subsequent reperfusion. METHODS: Experiments were conducted on the isolated perfused heart from vehicle and capsaicin-pretreated rats (100 mg/kg) to deplete neuropeptides from peripheral nerve terminals. The hearts were perfused with Krebs-Henseleit solution (95%O2 + 5% CO2, 37 degrees C, at constant pressure of 90 cmH2O). Left ventricular developed and diastolic pressures (LVDevP and LVEDP), heart rate (HR) and coronary flow (CF) were measured. Hearts were subjected to 20 min global no-flow ischemia and 30 min reperfusion. RESULTS: Prior to interrupting coronary flow, LV pressures, HR and CF did not differ between vehicle and capsaicin-pretreated rats. However, throughout the reperfusion period, the recovery of LVDevP, HR and CF in hearts from capsaicin-pretreated rats was consistently less than in control hearts (P < 0.05), and the incidence of fibrillation during reperfusion was higher (P < 0.05). In other experiments, acute perfusion of isolated hearts with capsaicin (10(-6) M) for 5 min before ischemia had a similar limiting effect during reperfusion. Administration of SP (10(-6)-10(-9) M) to capsaicin-pretreated hearts before ischemia restored their ability to recover contractile function and CF during reperfusion. Administration of SP to untreated hearts before ischemia also improved their recovery above normal during reperfusion and decreased the incidence of fibrillation without affecting postischemic CF. The beneficial effects of SP were abolished by an NK-1 receptor antagonist, CP-96,345 (10(-6) M). CONCLUSIONS: These data indicate that sensory neuropeptides play a role in protection of the isolated heart against ischemic damage and suggest a role of SP in the resistance of the myocardium to ischemia and reperfusion injury.

Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P < .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals.

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are known to be produced during prolonged ischemia and reperfusion, contribute to this afferent excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in 31 rats; the endings of these fibers were located in the left ventricle. Chemosensitive endings were identified with topical applications of capsaicin (10 micrograms) to the surface of the heart. Reactivity of the endings to oxygen-derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol). Activity of the vagal fibers was recorded during 30 minutes of occlusion of the left anterior descending coronary artery (LAD) and 10 minutes of subsequent reperfusion. The activity of chemosensitive endings within the ischemic zone increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9 impulses per second (107 +/- 30% increase, P < .05). This increased activity waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did not increase, their activity at the beginning of ischemia. Reperfusion caused a rapid elevation of activity only in chemosensitive fibers whose endings were found to respond to topical H2O2. The reperfusion-sensitive endings were located both within and outside the ischemic zone of the left ventricle. Indomethacin (5 mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of chemosensitive afferent endings at the beginning of LAD occlusion regardless of their sensitivity to H2O2 but had no effect on the activation at reperfusion.

[Adaptive stabilization of myocardium under the influence of electroacupuncture and cardiac protection]. / Vozniknovenie fenomena adaptatsionnoi stabilizatsii struktur miokarda pod vliianiem élektroakupunktury i zashchita serdtsa.

Adaptation of animals to short-term stress is known to result in the development of the adaptive structure stabilization phenomenon. At the level of the heart, the phenomenon appears as increased resistance to elevated catecholamine and calcium levels, reperfusion paradox. This study attempted to reproduce the phenomenon without applying any stress, but using a course of transauricular electric acupuncture. The isolated hearts of rats undergoing a course of the acupuncture were ascertained to show a clear-cut high resistance to the reperfusion paradox. After coronary ligation, the extent of necrosis in the animals having the acupuncture was significantly lower, as in those adapted to stress. The assumption that the phenomenon forming the basis for cardioprotective effects develops with electric acupuncture is discussed in the paper.

[The effect of experimental infarct and emotional-pain stress on the endothelium-dependent reactions of the isolated rat aorta]. / Vliianie éksperimental'nogo infarkta i émotsional'no-bolevogo stressa na éndoteliizavisimye reaktsii izolirovannoi aorty krysy.

Emotional-nociceptive stress, stress induced with a myocardial infarction, and stress following sham operation increased the effect of endothelium on the force and velocity of the smooth muscle contraction. Within 2 hrs after stress and 3 hrs after the coronary artery ligation, a considerable drop occurred in the rat arterial pressure followed by a facilitation of the aorta endothelium-dependent relaxation. Both these parameters were restored to the control level within 24 hrs. The facilitation of the endothelium-dependent relaxation of vascular wall seems to play a role in the drop of the vessels tone, in decrease of arterial pressure and, finally, in development of the cardiogenic shock in myocardial infarction in humans.

[Correlations between the endothelium-dependent relaxation of the aorta and arterial pressure in rats with myocardial infarction]. / Sootnoshenie éndoteliizavisimogo rasslableniia aorty i arterial'nogodavleniia krysy pri infarkte miokarda.

The effect of experimental myocardial infarction on endothelium-dependent relaxation was studied on isolated rat aorta and compared with the dynamics of arterial pressure (AP). It was shown that the endothelium-dependent relaxation of aorta was increased 1.8 times 3 h following the myocardial infarction. Simultaneously the drop in AP which had begun immediately following the experimental infarction became maximal. In 24 h both the indices were restored practically to the initial level. There was a significant negative correlation between the extent of endothelium-dependent relaxation and AP. It was suggested that the increase in endothelium-dependent relaxation could influence vascular tone, the drop in AP, and, finally, the development of cardiogenic shock in myocardial infarction in man.