Time- and order-dependent changes in functional and NO-mediated dilation during exercise training

Lash, Julia M., and H. Glenn Bohlen. Time- andorder-dependent changes in functional and NO-mediated dilation during exercise training. J. Appl. Physiol.82(2): 460-468, 1997.Arterial vessel responses to sodiumnitroprusside (SNP) and acetylcholine (ACh) were measured in thespinotrapezius muscle of sedentary (Sed) and treadmill-trained (Tr)rats to determine whether these endothelium-dependent (ACh) and-independent (SNP) mechanisms contribute to thetraining-induced increase in functional vasodilation previouslyobserved. Control and maximal vessel diameters were similar between Sedand Tr. After 8 wk of training, functional dilation (2-, 4-, and 8-Hzcontractions) was enhanced in all orders of vessels studied[terminal feed artery (FA), largest arterioles (1A), andintermediate-sized arterioles (2A)], but responses to SNP wereincreased only in FA. Responses to ACh were not significantly increasedin any vessel order. After 16 wk of training, functional dilation hadregressed in Tr such that only the FA response to 4 Hz wassignificantly elevated relative to Sed. However, the FA and 1Aresponses to SNP were significantly greater in Tr than in Sed, as werethe 1A and 2A responses to ACh. These results show a dissociation offunctional dilation and SNP- or ACh-mediated responses, as well asage-dependent interactions, a time-dependent progression, and vesselorder specificity in the adaptations to training.

     

Nonuniform effects of endurance exercise training on vasodilation in rat skeletal muscle.

Endurance exercise training (Ex) has been shown to increase maximal skeletal muscle blood flow. The purpose of this study was to test the hypothesis that increased endothelium-dependent vasodilation is associated with the Ex-induced increase in muscle blood flow. Furthermore, we hypothesized that enhanced endothelium-dependent dilation is confined to vessels in high-oxidative muscles that are recruited during Ex. To test these hypotheses, sedentary (Sed) and rats that underwent Ex (30 m/min x 10% grade, 60 min/day, 5 days/wk, 8-12 wk) were studied using three experimental approaches. Training effectiveness was evidenced by increased citrate synthase activity in soleus and vastus lateralis (red section) muscles (P < 0.05). Vasodilatory responses to the endothelium-dependent agent acetylcholine (ACh) in situ tended to be augmented by training in the red section of gastrocnemius muscle (RG; Sed: control, 0.69 +/- 0.12; ACh, 1.25 +/- 0.15; Ex: control, 0.86 +/- 0.17; ACh, 1.76 +/- 0.27 ml x min(-1) x 100 g(-1) x mmHg(-1); 0.05 < P < 0.10 for Ex vs. Sed during ACh). Responses to ACh in situ did not differ between Sed and Ex for either the soleus muscle or white section of gastrocnemius muscle (WG). Dilatory responses of second-order arterioles from the RG in vitro to flow (4-8 microl/min) and sodium nitroprusside (SNP; 10(-7) through 10(-4) M), but not ACh, were augmented in Ex (vs. Sed; P < 0.05). Dilatory responses to ACh, flow, and SNP of arterioles from soleus and WG muscles did not differ between Sed and Ex. Content of the endothelial isoform of nitric oxide synthase (eNOS) was increased in second-order, fourth-order, and fifth-order arterioles from the RG of Ex; eNOS content was similar between Sed and Ex in vessels from the soleus and WG muscles. These findings indicate that Ex induces endothelial adaptations in fast-twitch, oxidative, glycolytic skeletal muscle. These adaptations may contribute to enhanced skeletal muscle blood flow in endurance-trained individuals.     

Functional adaptations of rat skeletal muscle arterioles to aerobic exercise training.

This study tested the hypothesis that both structural and functional adaptations of arterioles occur within the skeletal muscle of rats aerobically trained for 8-10 wk with treadmill exercise. The training regimen used has been shown to elicit a 37% increase in plantaris citrate synthase activity but did not result in an elevation in citrate synthase activity in the spinotrapezius or gracilis muscles of rats used in this study. In the in vivo resting spinotrapezius muscle, arteriole diameters were similar in sedentary (SED) and trained (TR) rats. However, large- (1A) and intermediate- (2A) sized arterioles dilated proportionately more in TR than in SED rats during 1- to 8-Hz muscle contractions, even though the passive mechanical properties (circumference-passive wall tension relationships) were similar between groups. Vascular casts demonstrated a trend for an increase in the number of small (3A) arterioles and an approximately 20% increase in the passive diameter of 1A and 2A arterioles in the spinotrapezius muscle of TR rats. In contrast, in the gracilis muscle, arteriole diameters and density were identical in SED and TR rats, but the capillary-to-muscle fiber ratio was approximately 15% higher in TR rats. The results suggest that aerobic exercise training can greatly increase functional vasodilation and induce a slight increase in vascular density in skeletal muscle tissues, even if the oxidative capacity of these tissues is not increased by the training regimen.     

Improved functional vasodilation in obese Zucker rats following exercise training

Obese individuals exhibit impaired functional vasodilation and exercise performance. We have demonstrated in obese Zucker rats (OZ), a model of morbid obesity, that insulin resistance impairs functional vasodilation via an increased thromboxane receptor (TP)-mediated vasoconstriction. Chronic treadmill exercise training improves functional vasodilation in the spinotrapezius muscle of the OZ, but the mechanisms responsible for the improvement in functional vasodilation are not clear. Based on evidence that exercise training improves insulin resistance, we hypothesized that, in the OZ, exercise training increases functional vasodilation and exercise capability due to decreases TP-mediated vasoconstriction associated with improved insulin sensitivity. Six-week-old lean Zucker rats (LZ) and OZ were exercised on a treadmill (24 m/min, 30 min/day, 5 days/wk) for 6 wk. An oral glucose tolerance test was performed at the end of the training period. We measured functional vasodilation in both exercise trained (spinotrapezius) and nonexercise trained (cremaster) muscles to determine whether the improved functional vasodilation following exercise training in OZ is due to a systemic improved insulin resistance. Compared with LZ, the sedentary OZ exhibited impairments in glucose tolerance and functional vasodilation in both muscles. The TP antagonist SQ-29548 improved the vasodilator responses in the sedentary OZ with no effect in the LZ. Exercising training of the LZ increased the functional vasodilation in spinotrapezius muscle, with no effect in the cremaster muscle. Exercising training of the OZ improved glucose tolerance, along with increased functional vasodilation, in both the spinotrapezius and cremaster muscles. SQ-29548 treatment had no effect on the vasodilator responses in either cremaster or spinotrapezius muscles of the exercise-trained OZ. These results suggest that, in the OZ, there is a global effect of exercising training to improve insulin resistance and increase functional vasodilation via a decreased TP-mediated vasoconstriction.     

Pressure dependence of baroreceptor-mediated vasoconstriction in rat skeletal muscle

To determine whether microvessels in resting or contracting skeletal muscle constrict during baroreceptor activation, vascular diameters were measured in the spinotrapezius muscle of adult rats (n = 12) during occlusion of the common carotid arteries. Neural and myogenic components were distinguished using two types of occlusion: 1) "normal" (arterial pressure was allowed to increase with baroreceptor activation) and 2) "isobaric" (arterial pressure was maintained constant by decreasing blood volume). During normal occlusions, intermediate and small arteriolar diameters decreased in resting and contracting muscle (10-15% and 25-30%, respectively). Large arterioles and all-sized venules distended slightly (approximately 5%) in resting muscle, but diameters were maintained or decreased in contracting muscle. When arterial pressure was maintained constant (isobaric), the microvascular responses to baroreceptor activation in both resting and contracting muscle were essentially eliminated. We conclude that nearly all the arteriolar constriction observed in the spinotrapezius muscle during normal carotid artery occlusion is myogenic in origin, secondary to increased arterial pressure. This pressure-dependent constriction is augmented during skeletal muscle contraction and functional vasodilation.     

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits.

Exercise training is known to improve vasodilating mechanisms mediated by endothelium-dependent relaxing factors in the cardiac and skeletal muscle vascular beds. However, the effects of exercise training on visceral vascular reactivity, including the renal circulation, are still unclear. We used the experimental model of the isolated perfused rabbit kidney, which involves both the renal macro- and microcirculation, to test the hypothesis that exercise training improves vasodilator mechanisms in the entire renal circulation. New Zealand White rabbits were pen confined (Sed; n = 24) or treadmill trained (0% grade) for 5 days/wk at a speed of 18 m/min during 60 min over a 12-wk period (ExT; n = 24). Kidneys isolated from Sed and ExT rabbits were continuously perfused in a nonrecirculating system under conditions of constant flow and precontracted with norepinephrine (NE). We assessed the effects of exercise training on renal vascular reactivity using endothelial-dependent [acetylcholine (ACh) and bradykinin (BK)] and -independent [sodium nitroprusside (SNP)] vasodilators. ACh induced marked and dose-related vasodilator responses in kidneys from Sed rabbits, the reduction in perfusion pressure reaching 41 +/- 8% (n = 6; P < 0.05). In the kidneys from ExT rabbits, vasodilation induced by ACh was significantly enhanced to 54 +/- 6% (n = 6; P < 0.05). In contrast, BK-induced renal vasodilation was not enhanced by training [19 +/- 8 and 13 +/- 4% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P > 0.05)]. Continuous perfusion of isolated kidneys from ExT animals with N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), an inhibitor of nitric oxide (NO) biosynthesis, completely blunted the additional vasodilation elicited by ACh [reduction in perfusion pressure of 54 +/- 6 and 38 +/- 5% for ExT and L-NAME + ExT, respectively (n = 6; P < 0.05)]. On the other hand, L-NAME infusion did not affect ACh-induced vasodilation in Sed animals. Exercise training also increased renal vasodilation induced by SNP [36 +/- 7 and 45 +/- 10% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P < 0.05)]. It is concluded that exercise training alters the rabbit kidney vascular reactivity, enhancing endothelium-dependent and -independent renal vasodilation. This effect seems to be related not only to an increased bioavailability of NO but also to the enhanced responsiveness of the renal vascular smooth muscle to NO.     

Effects of aging and exercise training on spinotrapezius muscle microvascular PO2 dynamics and vasomotor control

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O(2) delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O(2) delivery to O(2) uptake, evidenced through improved microvascular Po(2) (Pm(O(2))), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ～6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify Pm(O(2)) in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline Pm(O(2)) (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting Pm(O(2)) and the time-delay before Pm(O(2)) fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the Pm(O(2)) in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.     

Interval sprint training enhances endothelial function and eNOS content in some arteries that perfuse white gastrocnemius muscle.

The purpose of this study was to test the hypothesis that interval sprint training (IST) selectively increases endothelium-dependent dilation (EDD) and endothelial nitric oxide synthase and/or superoxide dismutase-1 protein content in arteries and/or arterioles that perfuse the white portion of rat gastrocnemius muscle (WG). Male Sprague-Dawley rats completed 10 wk of IST (n = 62) or remained sedentary (Sed) (n = 63). IST rats performed six 2.5-min exercise bouts, with 4.5 min of rest between bouts (60 m/min, 15% incline), 5 days/wk. EDD was assessed from acetylcholine (ACh)-induced increases in muscle blood flow measured in situ and by ACh-induced dilation of arteries and arterioles [first to third order (1A-3A)] that perfuse red gastrocnemius muscle (RG) and WG. Artery protein content was determined with immunoblot analysis. ACh-induced increases in blood flow were enhanced in WG of IST rats. eNOS content was increased in conduit arteries, gastrocnemius feed artery, and fourth-order arterioles from WG and fifth-order arterioles of RG but not in 2As from RG. EDD was examined in 2As and 3As from a subset of IST and Sed rats. Arterioles were canulated with micropipettes, and intraluminal pressure was set at 60 cmH2O. Results indicate that passive diameter (measured in 0 calcium PSS) of WG 2As was similar in IST and Sed, whereas diameter of WG 3As was greater in IST (96 +/- 8 microm) than Sed (73 +/- 4 microm). WG 2As and 3As of IST rats exhibited greater spontaneous tone, but sensitivity to stretch, phenylephrine, and sodium nitroprusside was similar to Sed arterioles. ACh-induced dilation was enhanced by IST in WG 2As but not in RG 2As or WG 3As. We conclude that IST induces vascular adaptations nonuniformly among arteries that perfuse WG muscle.     

Time course of vasodilatory responses in skeletal muscle arterioles: role in hyperemia at onset of exercise

At the onset of dynamic exercise, muscle blood flow increases within 1-2 s. It has been postulated that local vasodilatory agents produced by the vascular endothelium or the muscle itself contribute to this response. We hypothesized that only vasodilators that act directly on the vascular smooth muscle could produce vasodilation of skeletal muscle arterioles in <2 s. To test this hypothesis, we determined the time course of the vasodilatory response of isolated skeletal muscle arterioles to direct application of potassium chloride, adenosine, acetylcholine, and sodium nitroprusside. Soleus and gastrocnemius muscles were dissected from the hindlimbs of male Sprague-Dawley rats. First-order arterioles (100-200 microm) were isolated, cannulated on micropipettes, and pressurized to 60 cmH(2)O in an organ bath. Vasodilatory agents were added directly to the bath, and diameter responses of the arterioles were recorded in real time on a videotape recorder. Frame-by-frame analysis of the diameter responses indicated that none of the vasodilator agents tested produced significant diameter increases in <4 s in either soleus or gastrocnemius muscle arterioles. These results indicate that, although these local vasodilators produce significant vasodilation of skeletal muscle resistance arterioles, these responses are not rapid enough (within 1-2 s) to contribute to the initiation of the exercise hyperemic response at the onset of dynamic exercise.     

Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane-receptor-mediated vasoconstriction

Individuals with hyperglycemia exhibit impaired exercise performance and functional vasodilatory response. Based on the importance of arachidonic acid (AA) metabolites in functional vasodilation and the increased thromboxane-to-prostacyclin ratio in diabetes, we hypothesized that chronic hyperglycemia in diabetes increases thromboxane-receptor (TP)-mediated vasoconstriction, resulting in an attenuated functional vasodilation. Three groups of lean Zucker rats (8 wk) were used to test the effects of chronic hyperglycemia on endothelial function: normal, streptozotocin (STZ; 70 mg/kg ip), and STZ + insulin (2 U/day). After 4 wk of treatment, spinotrapezius arcade arterioles were chosen for microcirculatory observation. Arteriolar diameter was measured following muscle stimulation and 10 microM AA application in the absence and presence of 1 microM SQ-29548 (TP antagonist). STZ rats exhibited significantly higher fasting glucose levels and attenuated functional and AA-induced dilation compared with normal animals. SQ-29548 improved the vasodilatory responses in STZ rats but had no effect in controls. Insulin treatment normalized both the glucose levels and the vasodilatory responses, and SQ-29548 treatment had no effect on functional or AA-mediated vasodilation in STZ + insulin animals. These results suggest that the impaired functional vasodilation in diabetic rats is due to hyperglycemia-mediated increases in TP-mediated vasoconstriction.     

Effects of Pseudomonas aeruginosa endotoxin on vasodilation in the intact spinotrapezius muscle.

The purpose of this study was to determine whether short-term exposure to clinically relevant concentrations of Pseudomonas aeruginosa lipopolysaccharide (LPS) impairs vasoreactivity of resistance arterioles in the intact spinotrapezius muscle microcirculation and, if so, to determine the mechanisms mediating this response. Using intravital microscopy, we found that 60-min suffusion of P. aeruginosa LPS (0.03-3.0 microg/ml) on the in situ hamster spinotrapezius muscle elicited an immediate, profound, and prolonged concentration-dependent vasodilation (P < 0.05). This response was reversible once suffusion of P. aeruginosa LPS was stopped. Pretreatment with N(G)-nitro-L-arginine methyl ester (10.0 microM), a nonselective nitric oxide (NO) synthase inhibitor, but not N(G)-nitro-D-arginine methyl ester, abrogated P. aeruginosa LPS-induced vasodilation and elicited a small, albeit significant, vasoconstriction. Indomethacin had no significant effects on P. aeruginosa LPS-induced responses. P. aeruginosa LPS had no significant effects on acetylcholine- and nitroglycerin-induced vasodilation in the spinotrapezius muscle. Collectively, these data indicate that short-term exposure to clinically relevant concentrations of P. aeruginosa LPS evokes an immediate, potent, prolonged, and reversible NO-dependent, prostaglandin-independent vasodilation in skeletal muscles in vivo. We suggest this response could play an important role in the pathophysiology of the profound vasomotor dysfunction observed in the peripheral circulation of patients with P. aeruginosa sepsis syndrome.     

In vivo visualization of subendocardial arteriolar response in renovascular hypertensive hearts

Time-sequential responses to endothelium-dependent and -independent vasodilators and angiotensin-converting enzyme (ACE) inhibitors were studied in the subendocardial arterioles (Endo) of canine renovascular hypertension (HT) compared with subepicardial arterioles (Epi; both <120 microm) by charge-coupled device intravital microscope. Vascular responses to acetylcholine, papaverine, and cilazaprilat were compared between normotensive (NT) and HT dogs [4 wk and 12 wk of HT (4wHT and 12wHT)]. The acetylcholine-induced vasodilation of Endo in both 4wHT and 12wHT was smaller than that of NT (both P < 0.01 vs. 4wHT and 12wHT), and that of Epi was smaller than that of NT only in 12wHT (P < 0.05). The papaverine-induced vasodilation of Endo, but not Epi, was impaired only in 12wHT (both P < 0.01 vs. NT and 4wHT). Vasodilation by cilazaprilat remained unchanged at 4wHT and 12wHT in both Epi and Endo. In conclusion, at the early stage, the endothelium-dependent response of Endo was impaired, whereas at the later stage, the endothelium-dependent and -independent responses of Endo and the endothelium-dependent response of Epi were impaired. However, the vasodilatory responses to the ACE inhibitor were maintained in both Endo and Epi of HT.     

Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: association with caveolins and caveolae

Obesity is a risk factor for hypertension and other vascular disease. The aim of this study was to examine the effect of diet-induced obesity on endothelium-dependent dilation of rat cremaster muscle arterioles. Male Sprague-Dawley rats (213 ± 1 g) were fed a cafeteria-style high-fat or control diet for 16-20 wk. Control rats weighed 558 ± 7 g compared with obese rats 762 ± 12 g (n = 52-56; P < 0.05). Diet-induced obesity had no effect on acetylcholine (ACh)-induced dilation of isolated, pressurized (70 mmHg) arterioles, but sodium nitroprusside (SNP)-induced vasodilation was enhanced. ACh-induced dilation of arterioles from control rats was abolished by a combination of the K(Ca) blockers apamin, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), and iberiotoxin (IBTX; all 0.1 μmol/l), with no apparent role for nitric oxide (NO). In arterioles from obese rats, however, IBTX had no effect on responses to ACh while the NO synthase (NOS)/guanylate cyclase inhibitors N(ω)-nitro-L-arginine methyl ester (L-NAME; 100 μmol/l)/1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μmol/l) partially inhibited ACh-induced dilation. Furthermore, NOS activity (but not endothelial NOS expression) was increased in arteries from obese rats. L-NAME/ODQ alone or removal of the endothelium constricted arterioles from obese but not control rats. Expression of caveolin-1 and -2 oligomers (but not monomers or caveolin-3) was increased in arterioles from obese rats. The number of caveolae was reduced in the endothelium of arteries, and caveolae density was increased at the ends of smooth muscle cells from obese rats. Diet-induced obesity abolished the contribution of large-conductance Ca(2+)-activated K(+) channel to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles, while increasing NOS activity and inducing an NO-dependent component.     

Effects of high-intensity intermittent swimming on glucose transport in rat epitrochlearis muscle

Recently (K. Kawanaka, I. Tabata, and M. Higuchi. J. Appl. Physiol. 83:429-433, 1997), we demonstrated that glucose transport activity after repeated 10-s-long in vitro tetani in rat epitrochlearis (Epi) muscle was negatively correlated with the postcontraction muscleglycogen concentration. Therefore, we examined whether high-intensityintermittent swimming, which depletes muscle glycogen to a lower levelthan that observed after ten 10-s-long in vitro tetani, elicits higherglucose transport than that observed after ten 10-s-long in vitrotetani, which has been regarded as the exercise-induced maximalstimulus for glucose transport. In male rats,2-deoxy-D-glucose transport rate in Epi muscle after eight bouts of high-intensity intermittent swimming with a weight equal to18% of body mass (exercise duration: 20 s, rest duration between exercise bouts: 40 s) was higher than that observed after the ten10-s-long tetani (2.25 ± 0.08 vs. 1.02 ± 0.16µmol · ml intracellular water¹ · 20 min¹). Muscleglycogen concentration in Epi after eight bouts of high-intensity intermittent swimming was significantly lower than that observed afterten 10-s-long in vitro tetani (7.6 ± 0.5 vs. 14.8 ± 1.4 µmolglucose/g muscle). These observations show that the high-intensity intermittent swimming increases glucose transport in rat Epi to a muchhigher level than that induced by ten 10-s-long in vitro tetani, whichhas been regarded as the exercise-related maximal stimulus for glucosetransport. Furthermore, this finding suggests that the lower muscleglycogen level after high-intensity intermittent swimming than after invitro tetani may play a role, because there was a significant negativecorrelation between glucose transport and muscle glycogen concentrationin Epi after high-intensity swimming and in vitro tetani.

     

Effect of standing on neurohumoral responses and plasma volume in healthy subjects

Upright posture leads to rapid pooling of blood inthe lower extremities and shifts plasma fluid into surrounding tissues. This results in a decrease in plasma volume (PV) and inhemoconcentration. There has been no integrative evaluation ofconcomitant neurohumoral and PV shifts with upright posture in normalsubjects. We studied 10 healthy subjects after 3 days of stableNa⁺ andK⁺ intake. PV wasassessed by the Evans blue dye method and by changes in hematocrit.Norepinephrine (NE), NE spillover, epinephrine (Epi), vasopressin,plasma renin activity, aldosterone, osmolarity, and kidney responseexpressed by urine osmolality and byNa⁺ andK⁺ excretion of the subjects inthe supine and standing postures were all measured. Wefound that PV fell by 13% (375 ± 35 ml plasma) over ~14 min,after which time it remained relatively stable. There was a concomitantdecrease in systolic blood pressure and an increase in heart rate thatpeaked at the time of maximal decrease in PV. Plasma Epi and NEincreased rapidly to this point. Epi approached baseline by 20 min ofstanding. NE spillover increased 80% and clearance decreased 30% with30 min of standing. The increase in plasma renin activity correlatedwith an increase in aldosterone. Vasopressin increased progressively,but there was no change in plasma osmolarity. The kidney responseshowed a significant decrease inNa⁺ and an increase inK⁺ excretion with upright posture.We conclude that a cascade of neurohumoral events occurs with uprightposture, some of which particularly coincide with the decrease in PV.Plasma Epi levels may contribute to the increment in heart rate withmaintained upright posture.

     

Age impairs Flk-1 signaling and NO-mediated vasodilation in coronary arterioles

Impairment of flow-induced vasodilation in coronary resistance arterioles may contribute to the decline in coronary vasodilatory reserve that occurs with advancing age. This study investigated the effects of age on flow-induced signaling and activation of nitric oxide (NO)-mediated vasodilation in coronary resistance arterioles. Coronary arterioles were isolated from young (approximately 6 mo) and old (approximately 24 mo) male Fischer-344 rats to assess vasodilation to flow, vascular endothelial growth factor (VEGF), and ACh. Flow- and VEGF-induced vasodilation of coronary arterioles was impaired with age (P相似文献   

Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles.

It has been hypothesized that microgravity-induced orthostatic hypotension may result from an exaggerated vasodilatory responsiveness of arteries. The purpose of this study was to determine whether skeletal muscle arterioles exhibit enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order arterioles isolated from soleus and white gastrocnemius muscles were tested in vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but diminished maximal vasodilation to Ado and SNP in both muscles. In addition, vasodilatory responses in arterioles from control rats varied between muscle types. Maximal dilations induced by Iso (soleus: 42 +/- 6%; white gastrocnemius: 60 +/- 7%) and Ado (soleus: 51 +/- 8%; white gastrocnemius: 81 +/- 6%) were greater in arterioles from white gastrocnemius muscles. These data do not support the hypothesis that microgravity-induced orthostatic hypotension results from an enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore, the data support the concept that dilatory responsiveness of arterioles varies in muscle composed of different fiber types.     

Time course of flow-induced vasodilation in skeletal muscle: contributions of dilator and constrictor mechanisms

The purpose of this study was to determine the time course of flow-induced vasodilation in soleus and gastrocnemius muscle arterioles and the mechanisms that underlie vasodilatory responses to an increase in intraluminal flow. Vasodilation was assessed during 20 min of continuous exposure to intraluminal flow. Both soleus and gastrocnemius muscle arterioles dilated in response to flow, although the magnitude of vasodilation was greater in arterioles from the gastrocnemius muscle. Neither blockade of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) nor blockade of cyclooxygenase with indomethacin inhibited the initial vasodilation (0-2 min) in arterioles from either muscle. In contrast, vasodilation to sustained exposure to flow (2-20 min) was eliminated by treatment with L-NAME in arterioles from both muscles. Both depolarization with 40 mM KCl and blockade of Ca(2+)-activated K(+) channels inhibited the initial flow-induced dilation, and the inhibition was greater in gastrocnemius muscle arterioles than soleus muscle arterioles. In the presence of L-NAME, prolonged exposure to flow resulted in constriction in soleus and gastrocnemius muscle arterioles. This constriction was abolished by endothelin receptor blockade. These results indicate that the time course and magnitude of flow-induced vasodilation differs between arterioles from soleus and gastrocnemius muscles. The immediate response to increased flow is greater in gastrocnemius muscle arterioles and involves activation of K(+) channels. In arterioles from both soleus and gastrocnemius muscles, vasodilation to sustained flow exposure occurs primarily through production of nitric oxide. In the absence of nitric oxide, sustained exposure to flow results in pronounced constriction that is mediated by endothelin.     

Sympathetic drive to liver and nonhepatic splanchnic tissue during heavy exercise

Coker, Robert H., Mahesh G. Krishna, D. Brooks Lacy, Eric J. Allen, and David H. Wasserman. Sympathetic drive to liver andnonhepatic splanchnic tissue during heavy exercise. J. Appl. Physiol. 82(4): 1244-1249, 1997.Thecontribution of sympathetic drive and vascular catecholamine deliveryto the splanchnic bed during heavy exercise was studied in dogs thatunderwent a laparotomy during which flow probes were implanted onto theportal vein and hepatic artery and catheters were inserted into thecarotid artery, portal vein, and hepatic vein. At least 16 days aftersurgery, dogs completed a 20-min heavy exercise protocol (mean workrate of 5.7 ± 1 miles/h, 20 ± 2% grade). Arterial epinephrine(Epi) and norepinephrine (NE) increased by ~500 and ~900 pg/ml,respectively, after 20 min of heavy exercise. Because Epi is notreleased from the splanchnic bed and because Epi fractional extraction(FX) = NE FX, NE uptake by splanchnic tissue can be calculated despite simultaneous release of NE. Basal nonhepatic splanchnic (NHS) FXincreased from a basal rate of 0.52 ± 0.09 to a peak of 0.64 ± 0.05 at 10 min of exercise. Hepatic Epi FX increased froma basal rate of 0.68 ± 0.10 to 0.81 ± 0.09 at 20 min of exercise. Even though NHS extraction of Epi reduced portal veinEpi levels by ~60%, the release of NE from NHS tissue maintainedportal vein NE at levels similar to those in arterial blood. NHS NEspillover increased from a basal rate of 5.7 ± 1.4 to 11.7 ± 2.8 ng · kg¹ · min¹at 20 min of exercise. Hepatic NE spillover increased from a basal rateof 5.0 ± 1.2 ng · kg¹ · min¹to a peak of 14.2 ± 2.8 ng · kg¹ · min¹at 15 min of exercise. These results show that1) approximately two- and threefoldincreases in NHS and hepatic NE spillover occur during heavy exercise,demonstrating that sympathetic drive to these tissues contributes tothe increase in circulating NE; 2) the high catecholamine FX by the NHS tissues results in an Epi level atthe liver that is considerably lower than that in the arterial blood;and 3) circulating NE delivery tothe liver is sustained despite high catecholamine FX due tosimultaneous NHS NE release.

     

Alterations in Nitric Oxide Activity and Sensitivity in Early Streptozotocin-Induced Diabetes Depend on Arteriolar Size

Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks'' streptozotocin-diabetic rats (n = 6) and of agematched controls (n = 8), basal inside diameters of A2–A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after N^G-nitro-L-arginine. In diabetic rats, cholinergic vasodilatation in A2–A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin-diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree.