Acta Physiologica

LINDBOM, L.; XIE, X.; RAUD, J.; HEDQVIST, P.

doi: 10.1111/j.1748-1716.1992.tb09442.xpmid: 1492559

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant‐induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose‐dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP‐induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.

AARS, H.; GAZELIUS, B.; EDWALL, L.; OLGART, L.

doi: 10.1111/j.1748-1716.1992.tb09443.xpmid: 1492560

In 15 subjects, laser‐Doppler flowmetry (LDF) was used to investigate whether the nervous control of pulpal blood flow (PBF) is affected by three tests known to excite the sympathetic nervous system. For comparison, skin blood flow was similarly recorded. Dynamic exercise (bicycle ergometer, 5 min, 90–100 W) in eight subjects was accompanied by a rise in PBF. PBF was increased by the cold pressor test (2 min) in eight subjects, while in five the flow decreased or remained unaffected. The isometric hand grip (2 min, 30% MVC) and the subsequent muscle ischaemia (2 min) led to a rise in PBF in two subjects and a fall in four. Following unilateral anaesthesia of the mandibular nerve, PBF in five subjects became unresponsive to dynamic exercise or the cold pressor test, indicating pressure autoregulation. All three tests triggered increases in mean arterial pressure (MAP) and heart rate (HR). Skin blood flow usually increased in response to the tests, but could also decrease, and often changed in a direction opposite to that of PBF. It is concluded that the circulation of blood in the human tooth is affected by evoked changes in autonomic nerve activity, involving activation of both vasodilator and vasoconstrictor nerves to vessels serving the tooth.

MORITA‐TSUZUKI, Y.; BOUSKELA, E.; HARDEBO, J. E.

doi: 10.1111/j.1748-1716.1992.tb09444.xpmid: 1492561

In the present study, changes in frequency and amplitude of the rhythmic variations (vasomotion) in blood flow in the intact cerebral circulation of the rat were investigated using laser‐Doppler flowmetry (LDF) during stepwise decrease in mean arterial blood pressure (MABP) and hyper‐and hypocapnia. Experiments were performed on 12 adult Sprague‐Dawley rats of either sex, anaesthetized with α‐chloralose. The rat's head was fixed on a stereotaxic frame and a small hole was made in the parietal bone but the dura and a thin inner bone layer were kept intact. The microvascular blood flow of the parietal cortex on the right or on both sides was continuously recorded by the laser‐Doppler flowmeter (Periflux PF2B, Perimed, Stockholm, Sweden). The cerebral circulation of the rat exhibited vasomotion in control conditions with a frequency of 8–10 cycles per minute (cpm) and an amplitude of 5–10% of the cerebral blood flow (CBF). No significant changes in CBF could be detected when the MABP was above 60 mmHg, but it decreased significantly when MABP was reduced below 50 mmHg. However, during stepwise pressure reduction the vasomotion frequency decreased progressively while its amplitude showed a reversed U‐shaped curve with a peak at 60–80 mmHg. During hypercapnia, the rhythmical oscillations showed a decrease in both frequency and amplitude, whereas during hypocapnia their frequency did not change but their amplitude increased. These results support the hypothesis that the vasomotion frequency might be dependent of the wall tension and cellular pH while its amplitude could be related to decreased tissue oxygenation.

TARASOVA, O. S.; RODIONOV, I. M.

doi: 10.1111/j.1748-1716.1992.tb09445.xpmid: 1362853

In urethane‐anaesthetized rats the effects of α‐adrenoceptor antagonists and desensitization of P2‐purinoceptors with α,β‐methylene ATP on the pressor reflex responses were investigated. Pressor responses were elicited by electrical stimulation of the central end of the sciatic nerve, by asphyxia and by occlusion of the common carotid artery. Responses to sciatic nerve stimulation and to asphyxia, but not those to carotid artery occlusion were entirely suppressed by dihydroergotamine and phentolamine. Under the action of dihydroergotamine the sinocarotid reflex decreased by over 70% in 40% of the experiments. In 60% of experiments the response was only slightly reduced or even augmented, but it was entirely inhibited by subsequent desensitization with α,β‐methylene ATP.

SAITO, M.; KAGAYA, A.; OGITA, F.; SHINOHARA, M.

doi: 10.1111/j.1748-1716.1992.tb09446.xpmid: 1492562

In order to examine efferent sympathetic nerve control of the peripheral circulation during exercise, muscle sympathetic nerve activity (MSNA), calf blood flow (CBF), heart rate (HR), blood pressure (BP) and oxygen uptake were measured during combined foot and forearm exercise. An initial period of rhythmic foot exercise (RFE) (60 min‐1 at 10% of maximal voluntary contraction (MVC) was followed by the addition of rhythmic handgrip exercise (RFE+OCCL) (60 min at 30% of MVC) and by forearm ischaemia after handgrip exercise while continuing RFE (RFE + OCCL). During RFE, CBF in the working leg, HR and oxygen increased respectively by 560%, 121% and 144% when compared with the control rest period, but MSNA (burst rate) was reduced by 13% (P > 0.05) and BP was unchanged. During RFE+RHG, HR, BP and oxygen uptake were greater than during RFE alone. There was no change in CBF, but a significant increase occurred in calf vascular resistance (CVR) and MSNA increased to 121% of the control level. During RFE + OCCL, MSNA, CVR and BP were all higher than during RFE alone, whereas HR and oxygen uptake decreased slightly, although they remained higher than the control values. The increase in CVR in the working leg and the rise in BP during RFE+RHG or RFE+OCCL might be linked to enhancement of MSNA, which may have been reflexly evoked by input from muscle metabolic receptors in the working forearm.

ULLMAN, J. E.; HJELMQVIST, H.; LUNDBERG, J. M.; RUNDGREN, M.

doi: 10.1111/j.1748-1716.1992.tb09447.xpmid: 1492563

The effect of separate and combined blockade of vasopressin (AVP) V1‐receptors and angiotensin II formation on resistance to a slow venous haemorrhage (0.7 ml kg‐1 min‐1) was studied in six conscious adult sheep by bleeding to the point of an abrupt fall in the mean systemic arterial pressure (MSAP). Intravenous administration of the V1‐receptor antagonist [d(CH2)5Tyr(Me)AVP] (10 μg kg‐1) and/or the angiotensin I converting enzyme inhibitor captopril (20 mg+1 mg h‐1) did not cause any significant haemodynamic changes in the normovolaemic animal. The volume of haemorrhage necessary to induce acute hypotension (MSAP < 50 mmHg) was significantly smaller after AVP blockade alone (13.8±0.7 ml kg‐1; P < 0.01) but not after captopril treatment (14.7±1.6 ml kg‐1; n.s.) compared to control animals receiving no drug treatment (16.8±0.6 ml kg‐1). The combined treatment with the AVP antagonist and captopril caused a further decrease in tolerance to haemorrhage (9.4±1.2 ml kg‐1; P < 0.001).

SAHLGREN, B.; EKLÖF, A‐CH.; APERIA, A.

doi: 10.1111/j.1748-1716.1992.tb09448.xpmid: 1492564

The regulation of the density of angiotensin II receptors in renal glomeruli in response to changes in salt intake is altered in Sprague‐Dawley rats with renovascular hypertension due to aortic constriction, and in hypertensive salt‐sensitive Dahl rats (Sahlgren 1989, Sahlgren & Aperia 1989). This study examines the modulatory role of sympathetic activity and arginine‐vasopressin on angiotensin II receptors in hypertensive Sprague‐Dawley rats with aortic constriction as well as in normotensive control rats. Denervation of the left kidney caused a 50% increase in the glomerular angiotensin II receptor density in the denervated kidney in both hypertensive rats and normotensive controls. An even more marked increase in glomerular receptor density occurred in both hypertensive rats and controls after blocking the sympathetic nervous system with guanethidine. To block the effects of arginine‐vasopressin we used a blocker of the V1‐receptors (predominant in vessels) and found an approximately 100% increase in the glomerular receptor density of angiotensin II in rats with aortic constriction. There was no reduction in blood pressure. Thus, on the receptor level the renin‐angiotensin system is markedly influenced by the activity of other major pressor systems.

LUNDBÆK, J. A.; HANSEN, A. J.

doi: 10.1111/j.1748-1716.1992.tb09449.xpmid: 1492565

The micro‐electrode method for determination of interstitial volume fraction (α) (Nicholson & Phillips 1981), was evaluated. The extracellular marker, tetramethylammonium+, is iontophoretically ejected from a micropipette and the change in concentration measured at a distance by an ion‐sensitive micro‐electrode and fitted to a diffusion equation. We used suspensions of human red blood cells as a model system and found that the values of α determined by this method and by haematocrit measurement were linearly correlated (r= 0.94) and not significantly different. The micro‐electrode method was used to characterize the interstitial space in rat brain cortex during normal conditions and during arrest of blood flow supply. Transport of solutes in interstitial space is governed by two characteristics, the interstitial volume fraction and the tortuosity factor. During control conditions, the interstitial volume fraction was 0.18±0.02 (mean±SEM), whereas it decreased to 0.07±0.01 in ischaemia. The tortuosity factor was 1.40±0.05 in controls and increased to 1.63±0.09 during ischaemia. Our measurements support the validity of the micro‐electrode method (Nicholson & Phillips 1981) and demonstrate that arrest of blood supply changes interstitial diffusional characteristics of brain cortex mainly by diminishing the size of the interstitial diffusional space.

LARSSON, L.; SALVIATI, G.

doi: 10.1111/j.1748-1716.1992.tb09450.xpmid: 1492566

Human muscle samples were obtained with the percutaneous biopsy technique. The samples were membrane‐hyperpermeabilized (skinned) using a chemical or freeze‐drying technique. Short single fibre segments were dissected from the sample, transferred to an experimental chamber, connected to a force transducer and manipulator, and exposed to temperature‐controlled solutions. The force generating‐capacity, the sensitivity of the contractile apparatus to calcium and the caffeine threshold for calcium release from the sarcoplasmic reticulum could be studied in the short muscle fibre segments obtained from man with the percutaneous muscle biopsy technique. The average length of the fibre segments between the connectors was 0.44±0.21 mm. Thus, detailed studies of the contractile machinery can be made on human skinned muscle fibres with only minimal discomfort to the patient or subject during biopsy, which should be useful in studies of neuromuscular disease, muscle plasticity or in applied physiology.

NELLGÅRD, B.; WIELOCH, T.

doi: 10.1111/j.1748-1716.1992.tb09451.xpmid: 1283483

The effect of different glutamate‐receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non‐competitive N‐methyl‐d‐aspartate (NMDA)‐receptor blocker, (±)‐5‐methyl‐10,11‐dihydro‐SH‐dibenzo(a, d)‐cyclo‐hepten‐5,10‐imine maleate (dizocilpine or MK‐801), (0. 30 μmol kg‐1 (0. 10 mg kg ‐1)), and the competitive NMDA‐receptor antagonists; cis‐4‐phosphonomethyl‐2‐piperidine carboxylate (CGS 19755), (3.36 μmol kg‐1 (0.75 mg kg‐1)), d‐(E)‐2‐amino‐4‐methyl‐5‐phosphono‐3‐pentenoic acid (CGP 40116), (1.20 μmol kg‐1 (0.25 mg kg‐1)) and its carboxylester CGP 43487, (6.30 μmol kg‐1 (1.50 mg kg‐1)). The α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepripriate (AMPA)‐receptor blocker, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(F) quinoxaline (NBQX), administered as an intravenous dose of 29.76 and 89.29 μmol kg‐1 (10 & 30 mg kg‐1), which is sufficient to block seizures and protect against ischaemic brain damage, did not inhibit spreading depression. None of the drugs utilized inhibited the anoxic membrane depolarization. The data demonstrate that NMDA‐receptor activation is essential for the initiation and propagation of spreading depression, while activation of AMPA‐receptors is not obligatory. The observed initiation and propagation of SD, during AMPA‐receptor blockade, suggest that activation of voltage‐operated ion channels may contribute to release the magnesium block of the NMDA‐receptor operated channel and to the initiation of SD.