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S Mellander

Publications and source records attributed to S Mellander.

13 recordsLinked to original sources

On the nature of basal vascular tone in cat skeletal muscle and its dependence on transmural pressure stimuli.

The aim of the present study was to elucidate in some detail the characteristics of the intrinsic basal vascular tone in the adrenergically blocked skeletal muscle with regard to its extent and site along the vascular bed, its dependence on arterial pressure via static and dynamic transmural pressure stimuli, and its sensitivity to local metabolic influence. Basal tone, which apparently is of myogenic nature, was pronounced in 'proximal arterial vessels' (greater than 25 mmicrometer i.d.) and in the 'microvessels' (less than 25 micrometers), but low in 'large veins'. Its functional characteristics, however, were different in the 'proximal arterial vessels' and the 'microvessels'. Normal basal tone in the 'microvessels' thus seemed to be intimately dependent on the arterial blood pressure level and, at least partly, initiated by its static mean pressure distension effect as well as by its dynamic pulse pressure oscillations. It could be virtually abolished by a transmural pressure decrease applied at fast rate ('strong inhibitory dynamic transmural pressure stimulus'). Basal tone in the 'proximal arterial vessels', on the other hand, was little affected by arterial pressure and almost irresponsive to transmural pressure stimuli. Basal tone in the 'microvessels' was much more sensitive to metabolic stimuli than that in the 'proximal arterial vessels'. The present results, viewed in the light of some recent electrophysiological studies on vascular smooth muscle, suggest that smooth muscle in the 'microvessels' is mainly of the spike-generating type, whereas that in the 'proximal arterial vessels' seems to be of different nature, possibly of the non-spike-generating type.

Adrenergic alpha-Antagonists

Characteristics of static and dynamic regulatory mechanisms in myogenic microvascular control.

The recently described static and dynamic components in myogenic microvascular control (Grände, Lundvall and Mellander 1977) were analysed in this study with regard to their stimulus-effector characteristics. Total and microvascular resistance responses in the sympathectomized vascular bed of skeletal muscle were analysed during graded changes of vascular transmural pressure (PT) applied at different rates (dPT/dt) in the range from +7.5 to -7.5 mmHg/s. The dynamic microvascular resistance responses, developing during the phase of changing PT, were pronounced and distinctly graded in relation to the magnitude of the dPT/dt stimulus, both with regard to amplitude of resistance response and rate of resistance change per unit time (dRmicro/dt). The static responses, revealed in the steady state phase of constant increased PT, were comparatively small and graded in relation to the amplitude of the PT increase. Rate-sensitivity in microvascular myogenic control was bi-directional, eliciting excitatory effects (constriction) in response to positive, and inhibitor effects (dilation) in response to negative, values of dPT/dt. The dynamic constrictor response to a given dPT/dt stimulus increased with increasing amplitude of PT and, thereby, increased duration of the dynamic stimulus. This effect might be explained by successive activation of myogenic "receptor units" with different thresholds. The described rate-sensitivity in the myogenic control system seems to increase its rapidity, stability, and sensitivity and thereby can contribute efficiently to well-adapted and refined microvascular adjustments.

Animals

Rate-dependent myogenic response of vascular smooth muscle during imposed changes in length and force.

A recent study of electrical and mechanical responses to stretch in isolated vascular smooth muscle revealed a clear-cut and graded influence of the rate of change in length, dL/dt (Johnansson and Mellander, 1975). This myogenic "dynamic" response at high rates of stretch was much more pronounced than the "static" response to constant, increased (+40%) length. In this previous study the mechanical responses were recorded as active force. In view of the fact that myogenic reactions in vivo must be associated with changes in vessel caliber, it was considered of interest to investigate the responses to stretch also in smooth muscle undergoing active shortening. In the present study, as in the one referred to above, electrical and mechanical activity in the isolated rat portal vein was studied by the sucrose gap method. However, in the present experiments the mechanical responses were recorded not only as active force but also as active shortening, making possible a comparison of the myogenic responses under these two types of smooth muscle contraction. Dynamic passive stretch was found to be associated with marked increase in spike discharge and mechanical activity under both these experimental conditions and the quantitative relation between spike discharge and rate of passive stretch (or shortening) was similar. Thus, active shortening of the smooth muscle did not interfere with the ability of the vessel to respond myogenically to passive stretch. A further analysis of the results suggested that, for the preparations as a whole, the dynamic excitatory response was more closely related to the rate of change of passive force, dP/dt, than to dL/dt.

Animals

Evidence for a rate-sensitive regulatory mechanism in myogenic microvascular control.

To reveal a possible rate-sensitive component in the myogenic control, changes of total and segmental vascular resistances in sympathectomized skeletal muscle in response to alteration of vascular transmural pressure (extravascular pressure) by 40 mmHg were compared when the pressure change was applied at two distinctly different rates (15 and 120 s). The papaverine-dilated vascular bed showed an entirely passive behaviour, whereas the normal, myogenically reactive vascular bed responded with active constriction upon transmural pressure increase and active dilation upon pressure decrease. These responses were especially pronounced in the microvessels where a clearcut two-component effector response was observed. The magnitude of the initial component was distinctly correlated to the rate at which the transmural pressure stimulus was applied, whereas the later steady state component during the static pressure change was rate-independent. At the high rate of pressure increase, the initial rate-dependent microvascular constrictor response was some ten times larger than the steady state response. These observations indicate the existence of a rate-sensitive as well as a static component in the myogenic response to changed transmural pressure, an interpretation strongly supported by a previous analogous study on isolated single-unit vascular smooth muscle (Johansson and Mellander 1975). It is concluded that the microvessels in skeletal muscle are highly responsive to myogenic stimuli and that emphasis should be placed on the dynamic rather than the static characteristics of the stimulus. Such rate-sensitivity in myogenic control would seem to facilitate prompt and proper vascular adjustments, for instance in myogenic autoregulation.

Animals

Hyperglycemic and hyperosmolar responses to graded hemorrhage.

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levles and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8. 20, and 25 mOsm/kg H2O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. --Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.

Animals

Circulatory effects evoded by 'physiological' increases of arterial osmolality.

The effects of moderate arterial hyperosmolality (+20 mOsm/kg H2O), produced by short term intravenous hypertonic infusion, on vascular resistance in skin, skeletal muscle, intestine, and kidney were analyzed in the anesthetized cat. Vascular resistance decreased in all four regions in response to the hypertonicity both before and after regional sympathectomy and the effects were not significantly altered by beta-adreno-ceptor blockade. Arterial blood pressure rose during the hypertonic infusion despite the decreased vascular resistance and an unchanged heart rate, indicating an increased stroke volume and cardiac output. Similar increases of arterial osmolality are known to occur in heavy exercise and in hemorrhage. The present results may therefore suggest that blood borne hyperosmolality is a factor which can contribute to the overall cardiovascular adjustments in these situations.

Animals

Circulatory and respiratory effects evoked by hypertonic ventriculo-cisternal perfusion.

The cerebral ventricular system of anesthetized dogs was perfused with synthetic isotonic CSF and, for 80 s intervals, with hypertonic CSF of various compositions. Hypertonic perfusion evoked centrally mediated marked increases in arterial blood pressure, heart rate, respiratory rate, and ventilation and, after some delay, an excitatory reaction resembling arousal. The responses were coordinated in time with the induced CSF hypertonicity, graded in relation to its magnitude, and reversible on return to isotonicity. The effects, which seemed to be elicited from periventricular structures in the brain stem, were more pronounced and consistent when CSF hypertonicity was produced by adding NaCl or Na-lactate than monosacharides to the isotonic CSF solution. Analysis of the cardiobascular responses indicated that they were caused by increased sympathetic vasoconstrictor and cardiac accelerance fibre activity and by inhibition of vagal discharge to the heart. The described pattern of response much resembles that evoked by physical exercise, a state which might lead to osmolar changes in the brain and CSF of a similar kind to that in the present study as a consequence of the pronounced work-induced arterial hyperosmolality. It is suggested that such an osmotic mechanism might constitute a "metabolic link" in the centrally mediated circulatory and respiratory adjustments in exercise.

Animals

Static and dynamic components in the vascular myogenic response to passive changes in length as revealed by electrical and mechanical recordings from the rat portal vein.

The effects of static and dynamic passive stretch and shortening on electrical activity and active force were analyzed in the isolated rat portal vein. Static stretch by 40% of muscle length evoked moderate excitatory effects with enhanced mechanical activity and an average increase in spike discharge of 12% above the control value of 55 plus or minus 2.6 spikes/min. The dynamic responses studied at various rates of length change (dL/dt) over the range between minus 12 and plus 12 mm/min, i.e., minus 3 and plus 3% muscle length/sec, were much more pronounced. Active force and spike activity showed graded increases with increasing rates of stretch. The electrical activity reached a value of 180 spikes/min (approximately equal to 325% of control) at 5 mm/min; this frequency was then maintained for stretch rates up to 12 mm/min. Mechanical activity during stretch was further reinforced by the shift along the length-tension diagram. Passive shortening at rates from minus 1 to minus 12 mm/min caused graded decreases in mechanical and electrical activity below the control levels, complete inhibition being observed at the latter dL/dt. Blockade of alpha and beta receptors indicated that the responses were myogenic in nature. The findings seem to provide direct support for the myogenic hypothesis of vascular tone and responses to stretch of the vascular wall, but they indicate that emphasis should be placed on the dynamic characteristics of the stimulus rather than its static nature. This emphasis constitutes a new concept in the myogenic control of the peripheral circulation.

Animals