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P O Grände

Publications and source records attributed to P O Grände.

8 recordsLinked to original sources

Myogenic microvascular responses to change of transmural pressure. A mathematical approach.

The recently described static and dynamic myogenic responses in the sympathectomized skeletal muscle microvessels to a given transmural pressure (PT) change applied at different rates (dPT/dt) (Grände & Mellander 1978), were further analysed in this study with a mathematical approach. The hypothesis that myogenic reactions are triggered by and related to wall tension was also tested. The mathematical model was based on a force-equilibrium in the microvessel wall including passive forces related to vascular transmural pressure, elasticity, and wall-viscosity, and active myogenic forces related to wall tension and its rate of change. Great resemblance was demonstrated between microvascular resistance curves obtained with the model and corresponding curves observed in vivo, indicating that the model quite adequately can describe myogenic microvascular resistance responses to transmural pressure stimuli. The results support the myogenic hypothesis in general and, in particular, the concept of an important rate-sensitivity in myogenic microvascular control and are compatible with the view that myogenic reactions are triggered by and related to change of wall tension. The model, in addition, provided data for certain microvascular variables which are difficult to assess by in vivo observations, e.g. Young's modulus of elasticity, wall tension, its rate of change, and internal vessel radius, and it offered a means to define more precisely the role of physical factors like effects of Poiseuille's and Laplace's laws in vascular resistance regulation.

Animals

Influence of neural and humoral beta-adrenoceptor stimulation on dynamic myogenic microvascular reactivity in cat skeletal muscle.

Analysis of myogenic microvascular reactivity in terms of its recently described prominent dynamic component was performed before and during graded sympathetic stimulation and catecholamine infusion. Phenoxybenzamine and propranolol were used to differentiate between alpha- and beta-adrenoceptor effects. The study first confirmed previous findings of a beta-adrenergic inhibitory component in the neural control of microvascular resistance which attenuated the alpha-adrenergic constriction. The results concerning the interaction between adrenergic and myogenic control mechanisms corroborated the conclusion that the sympathoadrenal system, via its beta-adrenergic link, exerts effective inhibitory action on myogenic excitatory reactions. As regards the neural control, its beta-adrenergic component seemed to quite precisely compensate for the reinforcing effect on the myogenic constrictor response which results from increased vascular tone per se (in this case caused by alpha-adrenergic constriction), interpreted as a physical 'gain' effect inherent in the inverse fourth power relationship between radius and resistance. The latter complicating factor, which implies non-linearity in integrated peripheral resistance control, was thus revealed only after beta-blockade, but not on the vascular bed with intact adrenoceptors, where a given transmural pressure stimulus evoked an almost equally large myogenic constrictor response irrespective of the prevailing level of vascular tone. The beta-inhibitory action of blood-borne noradrenaline was similar to the neural one, whereas that of adrenaline was more effective, causing decline of myogenic reactivity below control.

Adrenergic beta-Agonists

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

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

Transcapillary fluid movements in sympathectomized intestine and skin during hemorrhagic hypotension.

Net transcapilary fluid exchange in skin tissue (paw) and small intestine was observed during a 90 min period of hemorrhagic hypotension at 50 mm Hg in the cat. Reflex fluid transfer was prevented by regional sympathectomy and chi-adrenergic blockade. Early in hemorrhage, fluid absorption from the extravascular space occurred in both tissues, apparently caused by osmosis. The process was thus co-ordinated in time with a positive arterio-venous osmolar difference, in turn caused by a marked arterial hypersomolality. Experimetnal arterial hyperosomolality of similar magnitude, created by i.v. infusion of hypertonic glucose in non-bled animals, led to transcapillary fluid absorption in both intestine and skin and at rates similar to those in bleeding. Regional hypotsionen per se caused no fluid absorption. Later in hemorrhage (greater than 30 min), plasma fluid moved into the extravascular space both in skin and intestine, apparently due to a gradual increase of cappilary hydrostatic pressure. It is concluded that the arterial hypersomolality during bleeding can cause transcapillary fluid absorption in intestinal and skin tissues, as previously shown for skeletal muscle (Järhult 1973). The hemodynamic significance of this process for plasma volume regulation in hemorrhage is, however, much greater in skeletal muscle than in intestine and skin, mainly due to the much larger total mass of the muscle tissue.

Adrenergic alpha-Antagonists