Biomedical subjects

A I Soloviev

Publications and source records attributed to A I Soloviev.

5 recordsLinked to original sources

PubMed1993

Phospholipid vesicles (liposomes) restore endothelium-dependent cholinergic relaxation in thoracic aorta from spontaneously hypertensive rats.

OBJECTIVE: The present study was designed to examine, using isolated preparations of thoracic aorta, the effects of artificial phosphatidylcholine vesicles (liposomes) on vascular endothelium-dependent responses in spontaneously hypertensive rats (SHR) compared with those in Wistar-Kyoto (WKY) normotensive rats. DESIGN: Phosphatidylcholine liposomes, which possess the ability to repair the plasma membrane of living cells, were used in these experiments. METHODS: Liposomes were prepared from egg phosphatidylcholine. A suspension of lipid was subjected to ultrasound treatment at 20 degrees C at a frequency of 44 kHz for 45 s. The contraction of vascular smooth muscle was recorded using a force-displacement transducer coupled with a physiograph. RESULTS: It was shown that aortic smooth muscle from SHR demonstrated a loss of endothelium-dependent relaxation in acetylcholine (10(-6) mol/l) compared with WKY rat aortic smooth muscle. Liposomes in a concentration of 100-125 micrograms/ml restored these endothelium-dependent responses more effectively than L-arginine (10(-5) to 10(-4) mol/l), which is known to be a precursor of endothelium-derived relaxing factor (EDRF). This effect was not observed in denuded aortic rings, and liposomes lost their ability of repairing endothelium-dependent vascular relaxant responses in the presence of methylene blue (5 x 10(-5) mol/l), which inhibits soluble guanylyl cyclase activation by nitric oxide (NO), and N omega-nitro-L-arginine (L-NNA, 5 x 10(-5) to 10(-4) mol/l), a potent and selective inhibitor of NO synthase. CONCLUSION: The present results suggest that the loss of vascular endothelium-dependent responses in SHR may be, at least partly, due to endothelial cells membrane damage, and that the phosphatidylcholine liposomes can repair the function of endothelial cells and restore synthesis or release, or both, of EDRF in hypertension.

Acetylcholine↗

PubMed1993

Evidence for decrease in myofilament responsiveness to Ca2+ during hypoxia in spontaneously active vascular smooth muscle in rats.

The cellular mechanisms underlying smooth muscle hypoxic relaxation were examined in experiments on isolated chemically skinned muscle strips of rat portal vein. Low PO2 (3.9 kPa) shifted the pCa-tension relation to the right by 0.29 +/- 0.01 pCa units as compared to control curves (PO2, 18.8 kPa). Thus the Ca2+ sensitivity of the filaments had decreased. Addition of cyclic AMP (30 mumol l-1) with theophylline (5 mmol l-1) to the buffer solution produced a similar shift to low PO2. Low PO2 also decreased the maximal force to 40-50% of control. Inclusion of sodium fluoride (10 mmol l-1) and aluminium chloride (10 mumol l-1) in a bath solution caused partial (25-30%) relaxation of skinned smooth muscle preconstricted with 10 mumol l-1 Ca2+. The rate and amplitude of smooth muscle relaxation at low PO2 were significantly decreased by tolbutamide (5 mmol l-1), which is known to inhibit cyclic AMP-dependent protein kinases. We suggest that PO2 changes can alter myofilament responsiveness to Ca2+ and this effect may be related to cyclic AMP-dependent phosphorylation of myosin light chain kinase, its inactivation and subsequent uncoupling between Ca2+ and contractile machinery in smooth muscle.

Actin Cytoskeleton↗

PubMed1992

The contractile apparatus in vascular smooth muscle cells of spontaneously hypertensive rats possess increased calcium sensitivity: the possible role of protein kinase C.

OBJECTIVE: The purpose of the present investigation was to compare calcium sensitivity of contractile machinery in aorta and portal vein smooth muscle cells (SMC) in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive Okamoto rats (SHR), and to shed light upon the mechanisms of possible differences. DESIGN: Investigations into calcium sensitivity of SMC myofilaments can only be made on skinned muscular strips. METHODS: The vascular strips were made hyperpermeable by detergent skinning with saponin. The isometric calcium-induced contractions of SMC were recorded using a force displacement transducer coupled to a physiograph. RESULTS: It was shown that the pCa-tension (negative logarithm of calcium concentration versus tension) relationship for aorta and portal vein SMC in SHR shifted to the left in comparison with WKY rats. Putative protein kinase C inhibitors 1-(S-isoquionolinyl-sulfonyll)-2-methylpiperasine (H-7) and polymyxin B shifted the pCa-tension relationship more significantly to the right in the SMC of SHR than in WKY rats. It has also been shown that H-7 and polymyxin B sharply reduced the maximum tension developed by SMC in SHR whilst causing a non-significant decrease in maximum tension of SMC from WKY rats. These results are consistent with higher protein kinase C activity in SMC of SHR. CONCLUSION: These results indicate that the increase in calcium sensitivity of vascular SMC contractile machinery in SHR may be linked with the increase in their protein kinase C activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

Platelet-activating factor (PAF) induces contraction of saponin-skinned smooth muscle of coronary artery.

The effect of platelet-activating factor (PAF) on the development of isometric tension by saponin-skinned coronary artery was studied. PAF caused two types of contractions of coronary smooth muscle cells (SMC): (i) rapid, transient (phasic) contractions of SMC were induced by inositol 1,4,5-trisphosphate dependent Ca2+ release from sarcoplasmic reticulum (SR); (ii) slow sustained (tonic) contractions were induced by increase in Ca(2+)-sensitivity of the contractile apparatus of SMC by protein kinase C activation. The present results support the hypothesis that, in SMC of coronary artery, PAF receptors are located not only on the plasma membrane, but also on the SR membranes.

Animals↗

PubMedDate not supplied

Evidence for the involvement of protein kinase C in depression of endothelium-dependent vascular responses in spontaneously hypertensive rats.

The goal of the present study was to evaluate the role of protein kinase C (PKC) in the depression of endothelium-dependent vacular response in spontaneously hypertensive Okamoto rats (SHR). Aortae from SHR demonstrated a decreased relaxant response to acetylcholine (Ach) as compared to aortae from normotensive Wistar-Kyoto (WKY) rats, while papaverine lowered the force of aorta to a similar degree in both strains of rats. PKC inhibitors, H-7 (5 x 10(-6) M) and chelerythrine chloride (10(-6) M), produced a greater decrease in the force developed by the aortae from SHR vs. WKY rats both in intact and chemically permeabilized tissues. In SHR aortae PKC inhibitors enhanced relaxation to Ach to a greater extent as compared to WKY aortae. Furthermore, in the presence of PKC inhibitors, the constrictor responses of SHR aortae to Ach were transformed into relaxant responses, and the concentration-response curve to Ach was shifted to the left. The sensitivity of aortae from SHR to authentic nitric oxide (NO) was lowere compared to WKY rats. EC50s for authentic NO in SHR and WKY rat aortae were different: -2.9 +/- 0.15 x 10(-6) M and 4.58 +/- 0.1 x 10(-7) M (n = 15, p < 0. 001), respectively. Bioassay experiments using SHR aortae showed that the addition of chelerythrine (10(-6) M) to the detector superfusate caused relaxation during treatment of the donor segment with Ach, indicating that the sensitivity of the aortae to NO had been restored. When SHR detector ring was substituted for denuded aortae from WKY rats and PKC inhibitors were not added to the detector superfusate, the relaxation of the detector aortae was also close to the normal Ach-induced relaxation. WKY aortae demonstrated a positive relationship between Ach-stimulated NO release and relaxant response amplitudes (correlation coefficient r = 0.905, p < 0.001, n = 10). In contrast, there was a significant negative correlation in SHR aortae (r = -0.712, p < 0.05, n = 10). Detection of NO release by chemiluminescence showed no significant difference in NO release in SHR and WKY aortae. Taken together, these data suggest that the blunted endothelium-dependent relaxations seen in SHR aortae are mainly due to a decreased sensitivity of vascular smooth muscle to EDRF/NO resulting from an increased PKC activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗