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.

[Cellular mechanisms of the development of primary arterial hypertension]. / Kletochnye mekhanizmy razvitiia pervichnoi arteria'lnoi gipertenzii.

Modern views on the contraction and dilatation mechanisms of vessel smooth muscle cells are discussed. The data on main role of the cation-transport cell system function peculiarities in the primary arterial hypertension genesis, a relation cell hyperreactivity to those peculiarities and its genetical origin, are reported. It is supposed that the hereditary predisposition forms certain functional lability of cellular elements in different organism tissues, and, in consequence of that, the environmental influences can provoke the development of primary arterial hypertension.

[Endothelial modulation of arterial smooth muscle reactions to biological amines and electrical stimulation]. / Modulirovanie éndoteliem reaktsii gladkikh myshts arterii na biologicheskie aminy i élektricheskuiu stimuliatsiiu.

The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), acetylcholine (Ach), ATP and electrical stimulation (ES) were studied in isolated porcine epicardial coronary artery and the rat thoracic aorta preparations. A dose-dependent contraction of vascular smooth muscle (VSM) segments with endothelium in response to biological amines (10(-7)-10(-5) M) and ES (2-16 Hz, 20 msec, 50 V) was demonstrated. Removal of the endothelium abolished the dilatory effect of the ATP (10(-5) M), Ach (10(-7) M), but potentiated the constrictor responses of the VSM to 5-HT, NA, ES. The results corroborate the hypothesis that the endothelium-derived relaxing factor, first, promotes the effect of vasodilators and, second, limits the vasoconstrictory effect to endogenous neurohumoral stimuli and plays a major role in the protection against a vasospasm.

[Cellular mechanisms of transitory smooth muscle contraction of the coronary arteries during hypoxia: role of intracellular Ca2+]. / Kletochnye mekhanizmy tranzitornogo sokrashcheniia gladkikh myshts koronarnykh arterii pri gipoksii: rol' vnutrikletochnogo Ca2+.

In experiments on isolated porcine and canine coronary artery rings it was shown that vascular smooth muscle (VSM) during hypoxia (decreasing bath PO2 with 147 to 20-15 mm Hg) response to biphasic constriction-dilation reaction. Transient hypoxic contractions (THC) of VSM preserved completely in Ca2+-free solution and partially (up 50-60%) in the presence of Ca2+-channel blockers, but abolished by procaine. THC of VSM skinned by saponin significantly depressed at depletion of Ca2+-store sarcoplasmic reticulum (SR) by caffeine nd abolished after SR destruction. THC is not linked with Na+-K+-ATPase inhibition because it preserved (or increased) at ouabain treatment. THC significantly depressed under selective glycolysis blockade by monoiodoacetic acid and pyruvate and also after inositol-1 monophosphatase inhibition by lithium (the phase of hypoxic relaxation of VSM was augmented in this condition). Our results indicate that transient contraction of coronary arteries under hypoxia may be mediated mainly by release of Ca2+ from SR and linked obviously with production of inositol-1,4,5-trisphosphate. The participation of glycolysis in this process is unknown.

[Magnesium ions and contractile activity of vascular smooth muscle cells in hypoxia]. / Iony magniia i sokratitel'naia aktivnost' gladkomyshechnykh kletok sosudov pri gipooksigenatsii.

In isolated smooth muscle of the rat portal vein removal of Mg2+ from perfusate induced rapid enhancement of frequency and amplitude of spontaneous contractions and decreased inhibiting effect of hypoxia on the smooth muscle contractile activity. Concomitant elevation of extracellular Ca2+ has no additional protective effect on the smooth muscle in hypoxia. Ten-fold lowering of Mg2+ content in buffer solution resulted in a significant rise in the tension of the smooth muscle activated by Ca2+. The data obtained suggest that protective effect of Mg2+-free solution on vascular smooth muscle in hypoxia may be mediated not only through increases intracellular Ca2+ concentration but also due to rising sensitivity of the smooth muscle cells contractile protein to Ca2+.

[Role of the endothelium in the development of the contractile reactions of vascular smooth muscle during decreased oxygenation]. / Rol' éndoteliia v razvitii sokratitel'nykh reaktsii sosudistykh gladkikh myshts pri snizhenii ikh oksigenatsii.

Noradrenaline-preactivated vascular smooth muscles (VSM) of the rat thoracic aorta showed two-phase reactions in response to decreased oxygenation: significant relaxation was preceded by transient constriction. When the endothelium was removed only VSM relaxation phase was retained, with no constriction observed. The data obtained suggest an endothelium-dependent nature of VSM constriction reaction to hypoxia, in contrast to endothelium-independent VSM relaxation. Intracellular calcium is also assumed to play an essential role in the formation of endothelium-dependent constriction VSM reaction to hypoxia.

[Effect of a glycolysis block in the vascular wall on the phasic activity of smooth muscles]. / Vliianie blokady glikoliza v sosudistoi stenke na faznuiu aktivnost' gladkikh myshts.

A study was made of contractile reactions of spontaneously active smooth muscles of the portal vein during selective inhibition of glycolysis. Use was made of monoiodoacetate to inhibit first phasic and then tonic contractions of the vascular smooth muscles (VSM). Combined use of monoiodoacetate and pyruvate selectively inhibited phasic activity alone. A hypothesis is advanced as to the role played by the glycolytic oscillator as the triggering mechanism by which rhythmic phasic contractile activity is formed.

[Changes in sympathetic activity in the renal and splenic nerves upon stimulation of bulbar nuclei during hypoxic hypoxia]. / Ob izmeneniiakh simpaticheskoi aktivnosti v pochehcnom i selezenochnom nervakh pri stimuliatsii bul'barnykh iader v usloviiakh gipoksicheskoi gipoksii.

Microinjections of acetylcholine into the cat ventral reticular nucleus and nucleus of tractus solitarii in acute hypoxic hypoxia induce much lesser changes of efferent activity in renal and splenic nerves than in normoxia. Stimulation of the ventral reticular nucleus in hypoxia induces more obvious shifts of the efferent nerve activity than stimulation of the tractus solitarius nucleus. Bulbar reflex influences on cat's renal vascular bed are much more reduced in hypoxia than on the splenic one.

[Changes in efferent activity in the renal and splenic nerves during stimulation of the bulbar reticular nucleus]. / Ob izmeneniiakh éfferentnoi aktivnosti v pochechnom i selezenochnom nervakh pri stimuliatsii bul'barnykh retikuliarnykh iader.

Acute experiments on cats have shown that stimulation of the paramedian and ventricular reticular nuclei produces clear-cut and consistent changes in efferent activity of renal and splenic nerves. These changes are far more pronounced after ventricular nucleus stimulation. The changes in sympathetic activity and SAD after stimulation of the nuclei were inconclusive, thus indicating a diffuse distribution of pressor and depressor neurons in these nuclei. Acetylcholine microinjections into the ventricular reticular nucleus was accompanied by more marked changes in the activity of the splenic nerve, whereas stimulation of the paramedian reticular nucleus affected to a greater measure the renal nerve.