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Biomedical subjects

S Mellander

Publications and source records attributed to S Mellander.

At least 37 records · Page 2Linked to original sources
PubMed1990

Role of endothelium-derived nitric oxide in the regulation of tonus in large-bore arterial resistance vessels, arterioles and veins in cat skeletal muscle.

The role of endothelium-derived nitric oxide in the regulation of vascular resistance (tonus) in cat skeletal muscle was studied with the use of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide formation from L-arginine. The study was performed with a whole-organ technique which permits simultaneous, continuous and quantitative recordings of resistance reactions in the whole vascular bed (RT) and in its three consecutive sections: large-bore arterial resistance vessels (greater than 25 microns; Ra,prox), small arterioles (less than 25 microns; Ra,micro) and veins (Rv). NG-monomethyl-L-arginine (3-100 mg kg-1 tissue, i.a.) induced a dose-dependent increase in resistance that was preferentially, but not selectively, confined to the large-bore arterial resistance vessels. At a maximally effective dose (100 mg kg-1), the nitric oxide inhibitor caused a marked constriction, within 5 min, on average increasing RT by 99%, Ra,prox by 138%, Ra,micro by 18% and Rv by 23%. The constrictor response to NG-monomethyl-L-arginine was long-lasting but disappeared gradually over a period of about 1 h. However, it could be abruptly abolished by excess L-arginine (300 mg kg-1, i.a.). The vasodilator response (RT) to acetylcholine was significantly attenuated in the presence of NG-monomethyl-L-arginine compared with the control response. The results suggested that nitric oxide formation from L-arginine by the vascular endothelium plays a fundamental role in the regulation of vascular resistance (tone) in vivo, with its main site of action located in the large-bore arterial resistance vessels.

Animals↗
PubMed1989

Metabolic control of large-bore arterial resistance vessels, arterioles, and veins in cat skeletal muscle during exercise.

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels greater than 25 microns, arterioles less than 25 microns, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation ('light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a 'metabolic vasodilator index'. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels in the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 +/- 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.

Animals↗
PubMed1989

Functional aspects of myogenic vascular control.

Recent in vivo observations, especially in skeletal muscle, of macro- and microvascular myogenic reactivity and its functional consequences suggest that myogenic regulatory mechanisms contribute directly or indirectly to circulatory homeostasis by exerting the following main functions: (1) A blood pressure-induced tonic excitatory function of the vasculature, thereby initiating a pronounced intrinsic myogenic basal tone in the arterial microvessels; (2) a homeostatic resistance function (high total peripheral resistance), mainly exerted by the myogenic tone and serving to maintain normal arterial pressure at rest; (3) functions serving to improve nutritional flow and exchange, exemplified by blood flow recruitment, capillary recruitment, adjustments to the capillary perfusion:diffusion ratio for optimum exchange in the heterogeneous capillary network, and reactive hyperaemia; and (4) protective functions directed against harmful circulatory effects of changes in blood pressure, exemplified by autoregulation of blood flow and autoregulation of capillary hydrostatic pressure during changes in arterial pressure, and by autoregulation of transcapillary filtration during a hydrostatic load on the vascular bed.

Animals↗
PubMed1989

Effects of hypertonic NaCl solution on the hamster cheek pouch microcirculation in normo- and hypovolemia.

The aim of this study was to evaluate the effects of a single, 10 min, intravenous infusion of a hypertonic NaCl solution [2400 mOsm/l; infused volume 0.35 +/- 0.03 ml (SEM)] on the hamster cheek pouch microcirculation during normovolemia and after acute bleeding to a hypotension level of about 40 mmHg. Upon bleeding, the arterial pressure dropped to 39 mu 1 mmHg, arterioles greater than 40 microns constricted 12 +/- 3% (from their control value), arterioles less than 40 microns dilated 6 +/- 2%, venules stayed largely unchanged, while RBC velocity and volume flow decreased 57 +/- 7% in all vessels. During the subsequent hypertonic NaCl infusion, the arterial pressure increased rapidly to a new steady state level of 66 +/- 3 mmHg. After the infusion, the large arterioles stayed constricted 11 +/- 1% and the small arterioles dilated 7 +/- 1% for a 1-h observation period. The venules constricted initially by 6 +/- 2% and returned to control diameter in 30-40 min. RBC velocity and calculated volume flow returned to the pre-hemorrhage control values in about 10 min for the arterioles and in 40 min for the venules. An identical hypertonic infusion given to normovolemic hamsters caused no significant alterations of the measured variables.

Animals↗
PubMed1988

Site of autoregulatory reactions in the vascular bed of cat skeletal muscle as determined with a new technique for segmental vascular resistance recordings.

An arterial and venous microcannulation technique was developed for circulatory studies in the cat gastrocnemius muscle which, based on detailed morphological and functional observations of the microvascular arrangement, seems to permit continuous recordings of pressure in arterioles (diameter approximately 25 microns) and capillary pressure. These variables in combination with measurements of arterial and venous pressure and blood flow provided a means of continuous simultaneous recordings of total as well as segmental resistances in defined sections of the vascular bed, viz. in large arterial vessels (diameter greater than 25 microns), arterioles (less than 25 microns), and on the venous side. This new technique was applied to a study of the site(s) of autoregulatory reactions along the vascular bed evoked by changes of arterial pressure over the range 50-150 mmHg. The results indicated that active autoregulation mainly occurred within arterioles smaller than about 25 microns. In larger arterial vessels concomitant moderate active smooth muscle adjustments barely balanced out the pressure-induced passive calibre changes, and the venous vessels did not seem to contribute actively to autoregulation, but exhibited a passive change in postcapillary resistance (Rven). The described pattern of response results in quite effective autoregulation of blood flow and capillary pressure (PC). The observed passive Rven change, via its effect on the pre- to postcapillary resistance ratio, seems to explain the fact that autoregulation of PC can be more efficient than flow autoregulation. The study also provided quantitative data for the level of active intrinsic vascular tone in defined consecutive sections of the muscle vascular bed at normal arterial pressure and for segmental redistributions of tone evoked by pressure alterations.

Animals↗
PubMed1987

Vasoactive intestinal polypeptide in relation to penile erection in the cat evoked by pelvic and hypogastric nerve stimulation.

The hemodynamics of penile erection were elucidated in the anesthetized cat by studying volumetrically determined erectile responses of the penis and penile blood flow during frequency-graded bilateral stimulation of the pelvic and the hypogastric nerves, selectively or in combination. The study also provided information on possible neurotransmitter mechanisms. The results indicated that the erectile response is mediated by both the pelvic and hypogastric nerves, operating synergistically to evoke a seemingly maximum erection. Optimum erectile responses for either nerve system were obtained at 16 Hz and threshold responses at 0.5 to one Hz. In the presence of atropine, the erectile response to selective stimulation of the pelvic and the hypogastric nerves, respectively, were clearly curtailed, suggesting a cholinergic mechanism to be partly responsible for the diversion of blood from the penile "resistance vessels" to the cavernous bodies, possibly accomplished via the opening of vessels with a shunt-like function. However, the magnitude of the erectile response to combined pelvic and hypogastric nerve stimulation seemed to be surprisingly little affected by muscarinic blockade. Selective stimulations of the pelvic and the hypogastric nerves, respectively, were both found to cause about a five-fold increase in VIP output from the penis, coordinated in time with the local blood flow increase during erection. These data suggest a VIP-ergic neurotransmitter mechanism to be involved in penile erection in the cat, possibly controlling the dilation of the penile arterial "resistance vessels."

Animals↗
PubMed1987

Method for continuous recording of hydrostatic exchange vessel pressure in cat skeletal muscle.

A venous microcannulation technique applied to the cat gastrocnemius muscle was developed which, based on morphological and functional demonstrations of anastomotic connections between two supplying segmental vascular circuits at the level of capillaries and/or post-capillary venules, seems to permit continuous recordings of hydrostatic pressure (denoted Pcvenule) transmitted from such anastomoses, that is, from a site close to the main fluid exchange vessels. For validity tests, such Pcvenule recordings were compared with simultaneous estimates of capillary pressure (Pc) with the isogravimetric technique (Pciso) and, further, with data for experimentally evoked changes of Pc derived from volumetric recordings of net transvascular fluid flux divided by the capillary filtration coefficient (delta Pcvol). Simultaneously obtained data for Pcvenule and Pciso showed close agreement, and the Pcvenule and Pcvol data showed a highly significant linear correlation over a wide range of Pc changes. These results indicate that reliable estimates of Pc can be obtained with the Pcvenule method. It allows for continuous Pc recordings without interfering with normal vascular reactivity and can be applied to non-isogravimetric conditions and combined with simultaneous observations of whole-organ transvascular fluid exchange. At normal arterial and venous pressures and vascular tone, Pcvenule averaged 16.2 +/- 0.2 mm Hg, at which a Starling fluid equilibrium prevailed, and increased with decreasing vascular tone, resulting in net transvascular fluid filtration.

Animals↗
PubMed1987

Autoregulation of capillary pressure and filtration in cat skeletal muscle in states of normal and reduced vascular tone.

The controversial hypothesis that capillary pressure (Pc) is autoregulated in response to arterial pressure (PA) alterations was tested in sympathectomized cat skeletal muscle by studying the relation between Pc and PA under conditions of well preserved vascular tone and reactivity, during papaverine-induced maximal vasodilatation (passive vascular bed), and during impaired vascular reactivity caused by preparatory surgery, or by low dose isoproterenol administration. The latter states resembled such under which Pc autoregulation unintentionally seems to have been studied previously. Capillary pressure was assessed with the Pcvenule method for continuous direct pressure recordings from capillaries/postcapillary venules (Mellander et al. 1987) and simultaneously derived from observed net transvascular fluid flux divided by CFC. Resistances in the whole vascular bed and in its pre- and postcapillary segments (Ra and Rv) were determined from recordings of blood flow, PA, Pc, and PV. During preserved vascular reactivity, Pc was found to be virtually constant, that is, almost perfectly autoregulated, over the PA range from 50 to 180 mmHg, whereas in the passive vascular bed there was a direct linear relation between Pc and PA (y = 0.137x + 11.69; r = 0.97). The delta Pc/delta PA ratio was about 1/70 in the normal reactive, and 1/7 in the passive, vascular bed, implying an increase in Pc by 1 mmHg for every 70 mmHg and every 7 mmHg increase in PA, respectively. Capillary pressure autoregulation was explained by precise adjustments of Ra/Rv in relation to PA elicited by myogenic and metabolic regulatory mechanisms. This protective reaction against plasma loss during increased PA was abolished during maximal vasodilation, and was much impaired by surgical trauma, partly via a beta-adrenergic inhibitory effect, and by isoproterenol, in turn causing gross transcapillary fluid fluxes. The latter findings might explain failing Pc autoregulation in some previous studies undertaken under seemingly similar conditions.

Adrenergic beta-Agonists↗
PubMed1984

An evaluation of the metabolic interaction with myogenic vascular reactivity during blood flow autoregulation.

An attempt was made to evaluate the possible metabolic interaction with myogenic vascular reactivity during autoregulation of blood flow in sympathectomized cat skeletal muscle. This was done by studying the extent to which a purely myogenic response, elicited by a standardized 2 s vascular transmural pressure impulse stimulus was altered when mean arterial inflow pressure was varied in the range from 160 down to 40 mmHg. The observations were made during the steady state blood flows encountered at the different pressure levels. The data were corrected for the effects of physical factors inherent in altered basal vascular tone and intravascular pressure with the aid of a mathematical model for purely myogenic responses. The results demonstrated a flow dependent decline in myogenic vascular reactivity during reduction of arterial pressure, even in the range where blood flow was autoregulated quite effectively. This suggested a significant metabolic interaction with myogenic reactivity, an interpretation corroborated by a similar decline in myogenic reactivity found during more defined activation of the vascular metabolic control system by graded light muscle exercise. The fact that a significant metabolic interaction was revealed even at such minute flow changes that occur in the autoregulatory range indicates a high 'gain' in the metabolic feedback interacting, directly or indirectly, with myogenic mechanisms in local vascular regulation.

Adrenergic alpha-Antagonists↗
PubMed1984

Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide.

The haemodynamics of erection were elucidated in the anaesthetized dog by analysing in quantitative terms the changes of penile arterial inflow, venous outflow and tissue volume during graded pelvic nerve stimulation. The study also provides information on possible neurotransmitter mechanisms of the erectile response. Erection evoked by pelvic nerve stimulation appeared to result from two main circulatory events: first, there was a prompt dilatation of the penile 'resistance vessels', causing a greatly increased arterial inflow which in the early phase bypassed the cavernous bodies and, hence, increased venous outflow to the same extent. Secondly, the erectile response proper began after a distinct delay (approximately equal to 20 s). This was apparently caused by sudden opening of low resistance 'shunt vessels' diverting part of the arterial inflow into the cavernous bodies, leading to rapid filling. During the filling phase arterial inflow greatly exceeded venous outflow, and returned to the venous outflow level again in the steady state of full erection. The initial dilator response seemed to ensure rapid erection by establishing a high pressure head from the arterial microvessels to the cavernous spaces. The threshold frequency for the penile vasodilator response to pelvic nerve stimulation was 1-2 Hz and was always higher for the erectile volume response, viz. 2-4 Hz. Maximal effects for both were obtained at 16 Hz, causing on the average a 25-fold increase in peak arterial inflow, a 17-fold increase in venous outflow and a 107% increase in penile volume. Muscarinic blockade by atropine caused no significant decrease in the blood flow response induced by pelvic nerve stimulation, but clearly curtailed the erectile response. This indicates that the dilatation of the penile 'resistance vessels' is mainly non-cholinergic in nature, whereas a cholinergic mechanism seems to contribute to the erectile volume response proper. Pelvic nerve stimulation caused a substantial output of vasoactive intestinal polypeptide (VIP) from the penis which was correlated in onset and duration to the vasodilator response. Intra-arterial (I.A.) infusion of VIP elicited moderate erection and a penile vasodilator response which resembled the neural response. Similar effects were evoked by I.A. infusion of substance P, but the output of this peptide from the penis during stimulation was poorly correlated to the vascular events. These in vivo observations indicate that VIP might be the neurotransmitter responsible for the non-cholinergic pelvic nerve induced penile vasodilatation.

Animals↗
PubMed1983

Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this peptide during pelvic nerve stimulation in the present experiments. However, substance P is rapidly inactivated and might possibly be involved in these responses. Stimulation of the pelvic nerves in bursts at high frequencies (up to 80 Hz), simulating a discharge pattern observed electrophysiologically in vivo, was effective in eliciting all the above responses, with the exception of the colonic contraction.

Animals↗
PubMed1982

Neural beta-adrenergic dilatation of the facial vein in man. Possible mechanism in emotional blushing.

Ring preparations of the superficial buccal segment of the human facial vein, taken from extirpated tissue in 12 patients during neck surgery, were studied in vitro. The vein developed a maintained intrinsic myogenic tone in response to passive stretch and was supplied with alpha- as well as beta-adrenoceptors, both of which could be influenced by transmural nerve stimulation (TNS) and noradrenaline. These unusual characteristics for a vein are basically similar to the ones described for the rabbit facial vein by Pegram, Bevan & Bevan (1976). In man there seemed to be an inter-individual difference with regard to the abundance of 'innervated' alpha- and beta-adrenoceptors. Facial vein specimens from some subjects thus responded with prompt and pronounced net dilatation to TNS with maximum at 4 Hz and those from others with net constriction with maximum at 16 Hz. The latter showed a reversal into neural beta-adrenergic dilatation after alpha-adrenergic blockade. The human external jugular vein was devoid of intrinsic tone and beta-adrenoceptors. It is tentatively proposed that a beta-adrenergic neuro-effector mechanism in superficial ramifications of the facial vein in man might be involved in the emotional blushing reaction.

Adult↗
PubMed1982

A mathematical description of the myogenic response in the microcirculation.

A mathematical model for description of static and dynamic myogenic responses to change of vascular transmural pressure in the arterioles of skeletal muscle was developed for the purpose of elucidating some basic characteristics of the myogenic vascular control system which have proved difficult to reveal by physiological observations alone. The model, which is a refined version of a previous one (Borgström & Grände 1979), is based on a force-equilibrium in the arteriolar wall, including passive forces related to vascular transmural pressure, wall elasticity, and wall viscosity, an active force related to resting vascular tone, and the active static and dynamic myogenic forces considered to be related to and triggered by wall tension (force) and its rate of change as indicated by our previous results. The effects of biological inertia, of shifts along the length--tension curve of the smooth muscle, and of pressure induced reactions in the more proximal arterial vessels were taken into account in the present force-equilibrium equation for the arterioles. Arteriolar wall viscosity was assumed to decrease with increasing rate of wall movement, a behaviour predicted by the model and corroborated by in vitro observations on larger vessels. The model was found capable of faithfully simulating microvascular myogenic responses in cat skeletal muscle in vivo in response to ramp as well as impulse transmural pressure stimuli over the entire biological range from maximum constriction to dilatation. With such characteristics, it can serve as a useful complement to physiological approaches in attempts to define more precisely the mode of operation of the myogenic control system and to reveal inherent complexities of biophysical factors and of interaction of other control mechanisms in microvascular regulation in vivo, as exemplified by presented tests and preliminary results.

Animals↗
PubMed1979

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↗
PubMed1978

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↗