Saline containing phosphatidylcholine liposomes possess the ability to restore endothelial function damaged resulting from gamma-irradiation.

The protective action of passive saline filled ("empty") phosphatidylcholine liposomes (PCL) on endothelial function was examined in thoracic aortas obtained from gamma irradiated (6 Gy) Chinchilla rabbits, and then verified in experiments on non-anesthetized and anesthetized rats. Acetylcholine (ACh)-induced vascular relaxant responses in isolated vascular tissues rats were used as the test of endothelial integrity and its functional ability. It was shown that when added to the bath solution (100 microg/ml), PCL effectively restored endothelium-dependent ACh relaxations of isolated vascular rings damaged resulting from gamma-irradiation but had no effect on endothelium-independent vascular responses to therapeutic nitric oxide (NO) donors. The liposomes were also without protective effect when injected to the rabbits intraperitoneally (30 mg/kg) 1 hour before irradiation. In contrast, PCL, being injected at the same dose 1 hour after radiation impact, promote normalization of both endothelium-dependent vascular responses to ACh and nitric oxide (NO) donors. PCL restored also the sensitivity of vascular tissues to authentic NO (aqueous NO solution) that was surprisingly increased after irradiation, and normalized relationship between ACh-stimulated NO release and relaxant response amplitudes in irradiated aortas. Experiments on non-anesthetized and anesthetized rats demonstrated that irradiation led to significant elevation in the level of arterial blood pressure without any changes in cardiac contractility. PCL administration (25 mg/kg, i.v.) effectively normalized an increased arterial blood pressure in irradiated animals. In conclusion, it appears that PCL due to its ability to normalize NO-dependent vascular tone control mechanisms might be worthwhile therapeutic approach in case of ionizing irradiation accident. These result support the concept that the depression of endothelium-dependent vascular responses after irradiation may be result of decreased NO bioavailability due to its conversion to less potent vasodilators during irradiation-induced oxidative attack.

[Character and mechanisms of changes in vascular wall reactivity in prolonged hypercholesterolemia]. / Kharakter i mekhanizmy izmenenii reaktivnosti sosudistoi stenki v usloviiakh dlitel'noi giperkholesterinemii.

Changes in the structure and functional properties of the vascular wall after 8 months of alimentary hypercholesterolemia (HCE) were studied. The experiments were conducted on the circular bands of the arch of the aorta in rabbits. Sharp inhibition of the reactivity of the vascular bands was established, which was associated first of all with thickening of the intima due to the development of fibro-atheromatous changes in it. At the same time, the smooth-muscle cells of the vascular wall maintained marked reactivity to various direct and receptor-mediated test effects. The functional significance of the endothelium in regulation of the vascular tonus, manifested by weakened endothelium-dependent relaxation, was sharply inhibited in the late stages of HCE. It is shown that reduction of the sensitivity of the smooth-muscle cells to the endothelium-dependent relaxation factor is the principal factor of weakening of the endothelium-dependent dilatational effects. After 8 months of HCE the aortic wall is capable of liberating a substance which is similar to the endothelium-dependent relaxation factor in its action, even when the thickened intima is completely removed.

[Efficacy of vascular wall protection from atherosclerotic damage using various calcium antagonists]. / Effektivnost' zashchity sosudistoi stenki ot ateroskleroticheskogo povrezhdeniia razlichnymi kal'tsievymi antagonistami.

The authors studied the effect of various calcium antagonists--verapamil (VP) and Mg2+ (MgCl2) on the character of affection of the vascular wall ulcer conditions of prolonged hypercholesterolemia (HCE). The blood cholesterol (CS) content increased by the end of the 8th month of HCE to eight-fold the value in intact animals. The specific atherosclerotic changes in this case occupied approximately 80% of the area of the thoracic aorta whose functional properties changed essentially. The values of constricting responses of bands to noradrenaline (NA) was 45% of that in intact rabbits, the dilatating responses to acetyl choline (AC) and nitroglycerin (NG) were 20% and 35% of those in intact animals, respectively. Combination of HCE with daily VP injection (1 mg) led to a decrease in the area of affection of the aorta by 20%, which hardly affected the severity of HCE. A slightly more pronounced than in animals only with HCE (controls) was the response of bands to NA, AC, and NG (by 5, 30, and 15%, respectively). The protective effect of MgCl2 (200 mg/kg) was more significant--the affected area of the thoracic aorta reduced by 50% as compared to the controls, the constricting response to NA was maintained at a level exceeding the control level by 25%, the dilatating responses to NG and AC exceeded the control values 2 and 1.5 times, respectively, on the average. The severity of HCE diminished by 50%. The results of the study indicate that the organic and, in particular, the inorganic blocking agents of the calcium canals possess a marked angioprotective action and may be applied for the prevention of vascular atherosclerosis.

[Functional state and adrenergic reactivity of the myocardium in experimental atherosclerosis]. / Funktsional'noe sostoianie i adrenoreaktivnost' miokarda pri éksperimental'nom ateroskleroze.

The authors studied the changes in the functional properties of a rabbit heart in protracted alimentary hypercholesterolemia (HCE). It is shown that HCE has a little effect on the characteristics of myocardial contractility and adrenergic sensitivity. In protracted HCE the probability of the occurrence of a myocardial own rhythm in response to the effect of isoprenaline increased. HCE with simultaneous vasopressin administration failed to change the contractile properties of the myocardium but had a marked effect on the adrenoreceptor apparatus. The sensitivity of muscles to isoprenaline and phenylephrine increased significantly. The possibility of the appearance of a myocardial own rhythm increased. The results of the study are indicative of the essential role of vasospasm in the development of atherosclerotic myocardial injuries.

[Effects of hypercholesterolemia on the electrical and contractile properties of the blood vessel wall]. / Vliianie giperkholesterinemii na élektricheskie i sokratitel'nye svoistva sosudistoi stenki.

The investigations were performed on the ring strips of rabbit aorta. The electrical activity of the vessels smooth muscle cells was registered by the "sucrose gap" method; the contractile activity of the strips was determined simultaneously. Experimental atherosclerosis was induced by keeping rabbits on a special diet enriched by cholesterol for 2 and 4 months. Strips were prepared with intact or mechanically removed endothelium. Hypercholesterolemia was shown to inhibit the reactivity of the vessel's wall to the weakening action of acetylcholine due to endothelial stimulation. The cause of these changes was the inhibition of the endothelial functional activity and inactivation of mechanisms by which endothelium influences smooth muscle cells.

Possible mechanism of adrenergic and nonadrenergic inhibition in intestinal smooth muscle cells.

Nonadrenergic synaptic transmission in circular and longitudinal smooth muscles of caecum preexposed to K-free solution for 4-5 h has been studied by means of sucrose gap technique. In addition, the effects of noradrenaline (NA) and ATP on these muscles were investigated under these conditions. The action of the above substances was accompanied by depolarization and contraction. NA induced a decrease in the membrane resistance. Addition of 0.5 mM Ba2+ to K-free solution intensified the depolarization. 1 mM of Mn2+ blocked depolarization and contraction. Intramural stimulation produced noncholinergic e.j.p.s blocked by TTX. Addition of 0.5 mM Ba2+ increased their amplitude. A reversal potential of both NA-induced depolarization and e.j.p. was in the range of + 10 to + 20 mV. It is supposed that e.j.p.s and depolarization observed in response to ATP and NA action are due to an increase in calcium permeability of the membrane.

[Properties of synaptic currents during non-adrenergic inhibition of the smooth muscle cells of the large intestine in the guinea pig]. / Svoistva sinapticheskikh tokov pri neadrenergicheskom tormozhenii gladkomyshechnykn kletok tolstogo kishechnika morskoi svinki.

Inhibitory junctional currents (IJCs) were recorded under voltage clamp conditions in response to brief transmural stimulation of the circular muscle of the guinea pig colon using the double sucrose gap method in the presence of atropine. The time course of IJC decay was approximately exponential 100-150 ms after the peak value. The IJC amplitude depended linearly on the membrane potential with the reversal potential (-70 mV) near the potassium equilibrium potential. The time constant (tau) of the IJC decay depended exponentially on the membrane potential and became e-fold decreased when the membrane was hyperpolarized approximately by 120 mV. Varying the quantal content of IJC caused an increase of tau upon rising the amount or transmitter released and its decrease with the depression of IJC. Application of ATP (10(-3)M) caused a decrease of tau and IJC amplitude, while apamine reduced the amplitude of IJC without any changes in their time course. The results are discussed in terms of a buffered diffusion hypothesis supposing a cooperative action of transmitter released on junctional receptors.