Effects of glyceryl trinitrate,nitroprusside and nitric oxide on arterial,venous and capillary functions in cat skeletal muscle in vivo

The aim of the present study was to analyse quantitatively, on a cat gastrocnemius preparation in vivo, the effects of i.a. or i.v. administered glyceryl trinitrate (GTN), sodium nitroprusside (SNP) or nitric oxide (NO dissolved in saline) on vascular resistance (tone) in the following consecutive vascular sections: Large-bore arterial resistance vessels (> 25 μm), small arterioles (< 25 μm), and the veins. Effects on hydrostatic capillary pressure (P_cv) and transcapillary fluid exchange were simultaneously recorded. Close-arterially infused GTN (1–4096μg kg tissue^-1 min^-1), SNP (0.5–32 %mUg kg tissue^-1 min^-1) and NO (0.14-0.82 mg kg tissue^-1 min^-1) elicited a generalized dose-dependent dilator response in all three sections, though with a preferential action on the arterial side. Further, these agents caused an increase in P_cv and transcapillary fluid filtration. The sites of action along the vascular bed of these exogenous vasodilators differed from that previously established for endogenous EDNO. Infusion of GTN, SNP and NO during EDNO blockade (L-NAME) could, therefore, not restore the vascular resistance distribution to that prevailing in the initial control state. Myogenic vascular reactivity to standardized transmural pressure stimuli was clearly depressed by GTN and SNP. Intravenously infused GTN (4–512 μg kg body wt^-1 min^-1) and SNP (4–64μg kg body wt^-1 min^-1) decreased arterial pressure and elicited, via reflex sympathetic activation, a dose-dependent vasoconstriction in skeletal muscle, a decrease in P_cv, and net transcapillary fluid absorption. The constrictor response thus overruled the direct dilator effect of the drugs. The plasma volume expansion known to result from long-term systematic administration of nitrovasodilators seems in part to be caused by transcapillary fluid absorption in skeletal muscle.     

Sympathetic a-adrenergic control of large-bore arterial vessels,arterioles and veins,and of capillary pressure and fluid exchange in whole-organ cat skeletal muscle

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (P_c), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (> 25 μm), arterioles (< 25 μm) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRU s^-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of P_c, in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in P_c, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.     

In vivo effects of endothelin-2, endothelin-3 and ETA receptor blockade on arterial,venous and capillary functions in cat skeletal muscle

Ekelund , U. 1994. In vivo effects of endothelin-2, endothelin-3 and ET_A receptor blockade on arterial, venous and capillary functions in cat skeletal muscle. Acta Physiol Scand 150, 47–56. Received 31 March 1993, accepted 25 May 1993. ISSN 0001–6772. Department of Physiology & Biophysics, University of Lund, Sweden. This study describes, in quantitative terms, the effects of endothelin-2 and endothelin-3 on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 /μm), small arterioles (< 25 μm) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle in vivo. Infusion of endothelin-2 or endothelin-3 (200–1600 ng kg^-1 min^-1, i.a.) elicited an initial transient dilation, followed by a dose-dependent, slowly developing constrictor response, being maintained after cessation of the infusion. At the dose of 400 ng kg^-1 min^-1 (n= 9), infused i.a. during 20 min, endothelin-2 caused an average increase in total regional vascular resistance of 80%, and endothelin-3 of 35%, and the site of constrictor action of both peptides was preferentially located to the small arterioles. Endothelin-2 also constricted the veins and, hence, evoked a pronounced capacitance response, whereas endothelin-3 was devoid of any venoconstrictor effect. This difference, via effects on the pre-/post-capillary resistance ratio, led to a more pronounced fall of capillary pressure in response to endothelin-3 than to endothelin-2. The new specific competitive ET_A receptor antagonist, FR 139317, abolished the vasoconstrictor response to both endothelin-2 and endothelin-3 in vivo, whereas the preceding vasodilator responses were unaffected. These results, taken together with those of our previous analogous study of the effects of endothelin-1, indicated that all three endothelins were approximately equally as effective in eliciting the transient dilator response in skeletal muscle in vivo, whereas the order of vasoconstrictor activity was endothelin-1 > endothelin-2 > endothelin-3. Due to an especially pronounced venoconstrictor activity of endothelin-1, this peptide, in contrast to endothelin-2 and -3, evoked a rise in capillary pressure, with a consequent net transcapillary fluid filtration and muscle tissue oedema formation. The results further indicated that the vasoconstrictor responses to all endothelins in skeletal muscle were mediated by the ET_A receptor, whereas the initial transient vasodilator responses seemed to be mediated by the ET_B receptor.     

Endogenous nitric oxide as a physiological regulator of vascular tone in cat skeletal muscle during haemorrhage

The problem whether endogenous nitric oxide (NO) may serve as a true physiological regulator of vascular tone in vivo was approached by testing its role during graded acute haemorrhage with the aid of the nitric oxide synthase (NOS) inhibitor l -NAME. The study was performed on the vascular bed of cat skeletal muscle with a technique permitting quantitative recordings of vascular resistance in the whole vascular bed (R_T) and in its consecutive sections, the proximal arterial resistance (‘feeder’) vessels (>25 μm; R_a,prox), the small arterioles (<25 μm) and the veins. NO blockade by close-arterial l -NAME infusion in the control situation increased R_T from 16.3 to 33.0 PRU (+102%), because of a selective increase in R_a,prox by 16.7 PRU. A 35% blood loss per se raised R_T from 13.6 to 21.7 PRU. Superimposed NO blockade in this state caused a much stronger vasoconstriction than in the control situation, increasing R_T to 60.9 PRU (+181%) and R_a,prox by 40.5 PRU, which indicated an ～2.4-fold increase (P< 0.001) in the NO dilator influence in the R_a,prox section above control. The effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased production of endothelium-derived nitric oxide (EDNO). The constrictor response to l -NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regulator of vascular tone in the arterial ‘feeder’ vessels during haemorrhage, serving to counterbalance to a significant extent the concomitant adrenergic constriction, and thereby preventing critical reduction of blood flow and untoward heterogeneous flow distribution within the tissue.     

Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); Perindopril group (n = 7); Perindopril + BK group (n = 7). An additional sham operation group (Sham group, n = 6) were also established. After 4 weeks, the left ventricle function, myocardial tissue morphology, myocardial collagen volume faction, infracted ventricular wall thickness, myocardial infarction area and neovascular formation were evaluated. Results: Combination treatment with perindopril and BK were showed significant improvement on LVEDV, LVEF and LVFS than MI group. Moreover, a significant improvement on LVEF was found in Perindopril + BK group than Perindopril group but not on LVEDV and LVFS between these two groups. Furthermore, neo-vessel density was significantly increased in Perindopril + BK group than other groups while no significant improvement on vessel density was found after the treatment of perindopril. In addition, myocardial infarction thickness improvement was found in Perindopril and group than MI group while combination treatment with perindopril and BK can significant improve the myocardial infarction thickness than perindopril only. Conclusions: Combination treatment with ACE inhibitor perindopril and BK can significantly improve the ventricle function in the rat model of myocardial infarction. Our data suggest BK can serve as adjuvant treatment in myocardial infarction treatment.     

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 > 25 μm, arterioles < 25 μm, 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 and 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.     

Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma

BACKGROUND: Nitric oxide, including that produced by endothelial constitutive nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lungs and may influence various aspects of airway homeostasis. Angiotensin-converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of angiotensin II, bradykinin, and substance P, all of which are potentially involved in the pathogenesis of asthma. An insertion-deletion polymorphism of the ACE gene has been shown to be associated with enzyme activity levels of ACE. To examine the possible involvement of the ecNOS and/or ACE genes as the genetic basis of bronchial asthma, we investigated whether there was any association between bronchial asthma and polymorphisms of the ecNOS and/or ACE genes. METHODS: A total of 310 patients with bronchial asthma and 121 healthy subjects took part in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. RESULTS: 1) The distribution of one genotype (bb) of ecNOS was significantly higher in the asthma group than in the control population. 2) The ACE genotype distribution was not significantly different between the control and the asthma groups. 3) In asthmatic patients, the ACE and ecNOS genotype distribution did not differ significantly among groups of patients with different severities of asthma. CONCLUSIONS: These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of asthma. However, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.     

Peripheral circulatory effects of pump perfusion on cat skeletal muscle with and without prostacyclin

The present study analyses the peripheral circulatory effects of pump perfusion on a sympathectomized cat skeletal muscle in terms of effects on segmental vascular resistances (large-bore arterial vessels, arterioles and veins), hydrostatic capillary pressure, capillary filtration coefficient, transcapillary filtration and autoregulation of blood flow. The effect of prostacyclin during pump perfusion was analysed to evaluate whether it interferes with the pump-induced vascular alterations, especially if it reduces transcapillary filtration through its capillary permeability decreasing effect. Pump perfusion initiates a marked vasodilation (from 17.3 to 10.1 PRU), an increase in hydrostatic capillary pressure, and a marked inhibition of myogenic reactivity and of autoregulation of blood flow. There was a slow restoration of vascular tone reaching a steady-state level somewhat below the autoperfusion value within 2 h. Pump perfusion did not change the capillary filtration coefficient, indicating that the capillary permeability was not increased. This implies that short-term pump-induced capillary leakage is more an effect of increase in hydrostatic capillary pressure, perhaps in combination with increased number of open capillaries, than of an increase in capillary permeability. Prostacyclin decreased capillary permeability by at least 22% but simultaneously increased hydrostatic capillary pressure, resulting in an unchanged filtration compared with the situation just after the starting of the pump. The results obtained show that experiments using pump perfusion should be interpreted with care due to the interference with normal peripheral vascular control. The results give reasonable explanations of the lowered blood pressure and transcapillary fluid loss during the clinical use of a heart-lung machine.     

Comparison of arterial and venous responses of skeletal muscle to combined adrenergic stimulation

Department of Normal Physiology, Academician I. P. Pavlov First Leningrad Medical Institute. Academician K. M. Bykov Department of Physiology of Visceral Systems, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 7, pp. 5–7, July, 1990.     

依那普利对自发性高血压大鼠心肌ACE和ACE2表达的影响

 目的 观察自发性高血压大鼠(spontaneously hypertensive rats, SHR)心肌的血管紧张素转换酶(angiotensin-converting enzyme, ACE)和ACE2的表达,以及依那普利干预的影响。方法 将15只SHR随机分为2组：SHR对照组(n=7)和依那普利组(n=8),分别给以安慰剂、依那普利15mg.kg-1.d-1灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、western blot蛋白质免疫印迹检测。同步取10只WKY大鼠作为正常血压对照组。结果SHR心肌的ACE的mRNA和蛋白质的表达都显著高于)WKY组(1.68±0.34 vs 0.33±0.12, P＜0.05;1.21±0.14 vs 0.71±0.11, P＜0.05),而ACE2 的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs 1.16±0.24, P＜0.05; 0.71±0.24 vs 1.22±0.14, P＜0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs 1.68±0.34, P＜0.01; 0.87±0.13 vs 1.21±0.14, P＜0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15, P＜0.05),对ACE2的蛋白表达无明显影响(0.42±0.22 vs 0.71±0.24, P＞0.05)。结论 SHR心肌ACE明显升高,ACE2显著降低,有利于血压上调。依那普利能降低ACE,提升ACE2,可能是血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitors, ACEI)的降压机制之一。     

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’ (>25 μm i.d.) and in the ‘microvessels’ (<25 μm), 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.     

In-vivo effects of endothelin-1 and ETa receptor blockade on arterial,venous and capillary functions in skeletal muscle

Results from in vitro studies have indicated that endothelin-1 is a main candidate for endothelium-derived contracting factors. The aim of this in vivo study was to describe in quantitative terms the effects of endothelin-1 (ET-1), and of ET_a receptor blockade, on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 μm), small arterioles (< 25 μm) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle. Endothelin-1 (100–1600 ng kg-1 min-1, i.a.) elicited, after an initial transient dilation, a strong dose-dependent constrictor response in all three consecutive vascular sections, yet with a preferential action on the small arterioles and the veins. The vasoconstriction developed very slowly over about 1 h and was also long-lasting after cessation of the infusion. Our main quantitative analysis refers to effects elicited by 20 min long i.a. infusions of ET-1 at a dose of 400 ng kg-1 min-1. At the end of this period, the peptide caused, on average, a three-fold increase in total regional vascular resistance, in turn explained by a 70% increase in large-bore arterial resistance, a 280% increase in arteriolar resistance and a 220% increase in venous resistance. The latter effect was also manifested as a pronounced capacitance response, and as a decrease in the pre- to post-capillary resistance ratio leading regularly to a rise in capillary pressure, net transcapillary fluid filtration and oedema formation which is unusual for a vasoconstrictor. The new specific competitive ET_A receptor antagonist FR 139317 was found to be fully effective in vivo, insofar as it abolished the constrictor response to endothelin-1. ET_A receptor blockade, or administration of phosphoramidon, an inhibitor of ET-1 production, did not influence the level of basal vascular tone, indicating no significant endogenous release of ET-1 under resting conditions. This contrasts to the established pronounced endogenous release of endothelium-derived nitric oxide. Finally, vascular myogenic regulation was found not to be mediated by ET-1. The results, taken together, suggest a possible role of ET-1 in long-term, rather than short-term, regulation of vascular tone in vivo, perhaps especially during pathophysiological conditions.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors N_G-monomethyl-l -arginine or N^G-nitro-l -arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels > 25 μm, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a ‘metabolic’ factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide. Nor did, endothelium-derived nitric oxide seem to play a role as a ‘metabolic’ mediator of the functional hyperaemia response to muscle exercise, since the magnitude of this response was the same in the absence and presence of endothelium-derived nitric oxide blockade.     

Differential availability/processing of decorin precursor in arterial and venous smooth muscle cells

The existence of specific differentiation markers for arterial smooth muscle (SM) cells is still a matter of debate. A clone named MM1 was isolated from a library of monoclonal antibodies to adult porcine aorta, which in vivo binds to arterial but not venous SM cells, except for the pulmonary vein. MM1 immunoreactivity in Western blotting involved bands in the range of M(r) 33-226 kDa, in both arterial and venous SM tissues. However, immunoprecipitation experiments revealed that MM1 bound to a 100-kDa polypeptide that was present only in the arterial SM extract. By mass spectrometry analysis of tryptic digests from MM1-positive 130- and 120-kDa polypeptides of aorta SM extract, the antigen recognized by the antibody was identified as a decorin precursor. Using a crude decorin preparation from this tissue MM1 reacted strongly with the 33-kDa polypeptide and this pattern did not change after chondroitinase ABC treatment. In vitro, decorin immunoreactivity was found in secreted grainy material produced by confluent arterial SM cells, although lesser amounts were also seen in venous SM cells. Western blotting of extracts from these cultures showed the presence of the 33-kDa band but not of the high-molecular-weight components, except for the 100-kDa monomer. The 100/33-kDa combination was more abundant in arterial SM cells than in the venous counterpart. In the early phase of neointima formation, induced by endothelial injury of the carotid artery or vein-to-artery transposition, the decorin precursor was not expressed, but it was up-regulated in the SM cells of the media underlying the neointima in both models. Collectively, these data suggest a different processing/utilization of the 100-kDa monomer of proteoglycan decorin in arterial and venous SM cells, which is abolished after vein injury.     

Responses of single arterioles in vivo in cat skeletal muscle to change in arterial pressure applied at different rates

The concept of a rate-dependent, dynamic as well as a static component in the myogenic control has been suggested in some previous in vitro and whole organ investigations. The present study is an attempt to reveal a dynamic component in the myogenic response directly on single arterioles by a vital microscopic technique. The study was made on the autonomically blocked vascular bed of cat tenuissimus muscle and performed by analysing the arteriolar diameter changes to an arterial pressure increase and decrease when applied at two different rates. The results demonstrate a transient, dynamic constrictor response upon the phasic increase in pressure and a transient, dynamic dilator response upon the phasic decrease in pressure, the magnitudes of which being related to the rate of the pressure change. The static response developing during the steady-state phase of constant increased pressure was also shown. The dynamic responses were confined to arterioles smaller than about 20 μm while the steady-state response was present in larger arterioles as well. Even if the metabolic control system partly could be responsible for the obtained responses, arguments are given that the described reactions are mainly myogenic in nature.     

Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in rabbit skeletal muscle

Gustafsson , U., Sjöberg , F., Lewis , D. H. & Thorborg , P. 1994. Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in rabbit skeletal muscle. Acta Physiol Stand 150, 39–45. Received 2 April 1993, accepted 21 July 1993. ISSN 0001–6772. Clinical Research Centre and the Burns Unit, Department of Hand and Plastic Surgery, and Department of Anaesthesiology, University Hospital, Linkoping, Sweden, and Dept of Anesthesiology, University of Rochester Medical Center, NY, USA. This study examined capillary flow and oxygenation in rabbit skeletal muscle during hypoxic hypoxia (inspired oxygen fraction = 0.10) and after administration of ritanserin (highly selective 5-Hydroxytryptamine-2-receptor antagonist). Capillary flow (hydrogen clearance) or oxygen pressure was measured with a multiwire micro-electrode which was placed on the surface of the left vastus medialis muscle. For measurement of regional microcirculatory blood flow a laser-Doppler flowmeter probe was placed on the contralateral muscle. An experimental sequence with normoxaemia (arterial Po₂ 12.5 kPa), followed by hypoxaemia (arterial Po₂ 3.9 kPa) and thereafter sustained hypoxaemia (arterial Po₂ 4.0 kPa) during which ritanserin (0.035 mg kg^-1 i.v.) was administered, was used. During hypoxaemia a decrease was seen in mean arterial pressure (MAP) by 27%, capillary flow by 25%, muscle oxygen pressure by 32% and laser-Doppler flowmetry (LDF) flow by 24%. After the administration of ritanserin the mean arterial pressure was further reduced by 7%, whereas the capillary flow increased by 59% and the muscle oxygen pressure by 31 %. The LDF flow remained unchanged. These results demonstrate that, in this animal model, a decrease in skeletal muscle capillary flow and oxygenation during hypoxaemia can be reversed by the administration of ritanserin, despite a further reduction in blood pressure.     

Changes in skeletal muscle size, fibre-type composition and capillary supply after chronic venous occlusion in rats

Aim: We have previously shown that surgical occlusion of some veins from skeletal muscle results in muscle hypertrophy without mechanical overloading in the rat. The present study investigated the changes in muscle‐fibre composition and capillary supply in hypertrophied muscles after venous occlusion in the rat hindlimb. Methods: Sixteen male Wistar rats were randomly assigned into two groups: (i) sham operated (sham‐operated group; n = 7); (ii) venous occluded for 2 weeks (2‐week‐occluded group; n = 9). At the end of the experimental period, specimens of the plantaris muscle were dissected from the hindlimbs and subjected to biochemical and histochemical analyses. Results: Two weeks after the occlusion, both the wet weight of plantaris muscle relative to body weight and absolute muscle weight showed significant increases in the 2‐week‐occluded group (～15%) when compared with those in the sham‐operated group. The concentrations of muscle glycogen and lactate were higher in the 2‐week‐occluded group, whereas staining intensity of muscle lipid droplets was lower in the 2‐week‐occluded group than those in the sham‐operated group. The percentage of type I muscle fibre decreased, whereas that of type IIb fibre increased in the 2‐week‐occluded group when compared with the sham‐operated group. Although the expression of vascular endothelial growth factor‐188 mRNA increased, the number of capillaries around the muscle fibres tended to decrease (P = 0.07). Conclusion: Chronic venous occlusion causes skeletal muscle hypertrophy with fibre‐type transition towards faster types and changes in contents of muscle metabolites.     

Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats

Since exercise capacity is related to the mitochondrial respiration rate in skeletal muscle and both parameters are potentially modulated by the onset of diabetes and by inhibition of the angiotensin-converting enzyme (ACE), we investigated whether skeletal muscle oxidative functions and exercise capacities are impaired in chronic streptozotocin-induced diabetic (STZ) rats and whether ACE inhibition could reverse such abnormalities. The ACE inhibitor perindopril (2 mg kg(-1) day(-1)) was given for a period of 5 weeks to 7-month-old STZ rats (DIA-PE, n = 8) whose haemodynamic function, skeletal muscle mitochondrial function and exercise capacity were compared with those of untreated diabetic (DIA, n = 8) and control rats (CONT, n = 8). Increased arterial blood pressure (157 +/- 12 versus 130 +/- 6 mmHg, P < 0.05) and reduced exercise capacity (29 +/- 2 versus 91 +/- 2 min, respectively, P < 0.01) were observed in DIA compared with CONT. The oxidative capacity of the gastrocnemius muscle was significantly reduced in DIA compared with CONT rats (5.4 +/- 0.5 versus 10.6 +/- 0.7 micromol O(2) min(-1)(g dry weight)(-1), respectively, P < 0.001). Moreover, the coupling between oxidation and phosphorylation was significantly impaired in DIA (-52%, P < 0.001). Angiotensin-converting enzyme inhibition (ACEi) normalized blood pressure without improving mitochondrial function (4.3 +/- 0.8 micromol O(2) min(-1) (g dry weight)(-1) in DIA-PE rats) but reduced exercise capacity to even lower levels (10 +/- 1 min, P < 0.01). Exercise capacity correlated positively with blood pressure in DIA-PE (r = 0.79, P < 0.05). In experimental type 1 diabetic rats, both skeletal muscle mitochondrial respiration and exercise capacity are impaired. The ACEi failed to restore the muscular function and worsened exercise capacity. Further studies will be useful to determine whether an inadequate muscular blood flow secondary to the reduction in mean systemic blood pressure can explain these results.     

L-精氨酸和一氧化氮抑制剂对大鼠血管钙化的影响

观察给予一氧化氮合酶(NOS)的抑制剂左旋硝基精氨酸(L-NNA)或底物L-精氨酸(L-Arg)对血管钙化的影响。利用维生素D3和尼古丁制备大鼠血管钙化模型，测定大鼠尾动脉压，血管钙含量、碱性磷酸酶活性及^45Ca沉积；并检测血管组织的L-Arg转运，NOS活性及NO2^-和cGMP含量。发现钙化大鼠血压略升高；动脉钙含量、ALP活性及^45Ca沉积明显增加，von Kossa染色可以看到明显的钙化颗粒；钙化血管组织NOS活性升高；NO和cGMP含量均减少。给予L-NNA或L-Arg后，与单纯钙化组相比，L-NNA干预组的L-Arg转运、NOS活性及NO和cGMP的含量均降低；而L-Arg干预组上述指标的变化正相反。同时，L-NNA干预组的钙化程度比钙化组加重，而L-Arg干预组的钙化程度比钙化组减轻；提示血管钙化时NO—NOS—cGMP途径发生紊乱，干预NO—NOS—cGMP途径可以影响钙化的进程。