Biomedical subjects

M H Laughlin

Publications and source records attributed to M H Laughlin.

At least 55 records · Page 3Linked to original sources

PubMed1998

Acetylcholine is a vasodilator of porcine skeletal muscle arteries.

The purpose of this study was to test the hypothesis that porcine skeletal muscle arteries exhibit concentration-dependent vasodilation in response to acetylcholine (ACH) as observed in other mammals. We conducted three experiments. First, vasorelaxation responses to ACH were examined in isolated segments of femoral and brachial arteries, mounted on myographs and studied in vitro. Second, we determined whether resistance arteries from porcine skeletal muscle exhibit vasodilation in response to ACH by isolating second order arterioles (2-A) from the medial (MHT), deep-long (LOH) and lateral (LAT) heads of the triceps brachii muscles of four pigs. The rationale for selection of arterioles from these muscles was that these muscles represent muscles composed primarily of slow-oxidative, fast-oxidative-glycolytic, and fast-glycolytic muscle fiber types, respectively. 2-As were isolated and cannulated with micropipettes and intraluminal pressure set at 60 cm H2O. In both sets of in vitro experiments, we determined responses to an endothelium-independent dilator, sodium nitroprusside (10(-10)-10(-4) M), and to endothelium-dependent agents ACH (10(-10)-10(-4) M), and bradykinin (BK; 10(-11)-10(-6) M). Third, we used transcutaneous ultrasound imaging to measure changes in artery diameters and Doppler-principle measurements of blood flow velocities to estimate changes in total blood flow in the femoral vascular bed. Results reveal that ACH and BK produced similar vasorelaxation responses in femoral and brachial arteries and vasodilation of skeletal muscle 2-As. Also, ACH produced increases in blood flow and decreases in vascular resistance in the femoral vascular bed. These results indicate that the arterial tree of porcine skeletal muscle exhibits ACH-induced, endothelium-dependent vasodilation.

Acetylcholine↗

PubMed1998

Regulation of skeletal muscle perfusion during exercise.

For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

Animals↗

PubMed1998

Exercise training-induced adaptations in the coronary circulation.

Aerobic exercise training induces an increase in coronary blood flow capacity that is associated with altered control of coronary vascular resistance and, therefore, coronary blood flow. The relative importance of metabolic, myogenic, endothelium-mediated, and neurohumoral control systems varies throughout the coronary arterial tree, and these control systems contribute in parallel to regulating coronary vascular resistance to differing degrees at each level in the coronary arterial tree. In addition to this nonuniformity of the relative importance of vascular control systems in the coronary arterial tree, it appears that exercise training-induced adaptations are also distributed spatially, in a nonuniform manner throughout the coronary tree. As a result, it is necessary to examine training-induced adaptations throughout the coronary arterial tree. Adaptations in endothelium-mediated control play a role in training-induced changes in control of coronary vascular resistance, and there is evidence that the effects of training may be different in large coronary arteries than in the microcirculation. Also, there is evidence that the mode, frequency, and intensity of exercise training bouts and duration of training may influence the adaptive changes in endothelial function. Exercise training has also been shown to induce changes in responses of coronary vascular smooth muscle to vasoactive agents and alterations in the cellular-molecular control of intracellular Ca2+ in coronary vascular smooth muscle of conduit coronary arteries and to enhance myogenic reactivity of coronary resistance arteries. Exercise training also appears to have different effects on vascular smooth muscle in large coronary arteries than in the microcirculation. For example, adenosine sensitivity is increased in conduit coronary arteries and large resistance arteries after training but is not altered in small coronary resistance arteries of trained animals. Although much remains to be studied, evidence clearly indicates that chronic exercise alters the phenotype of coronary endothelial and vascular smooth muscle cells and that plasticity of these cells plays a role in adaptation of the cardiovascular system in exercise training.

Acetylcholine↗

PubMed1998

Effects of hyperthyroidism on vascular contractile and relaxation responses.

Previous research has shown that skeletal muscle blood flow, at rest and during muscular contractions, is elevated in the hyperthyroid state. We hypothesized that reduced vascular contractile and enhanced endothelium-dependent relaxation responses contribute to these observations. To test these hypotheses, male rats were administered triiodothyronine (Hyper, n = 27; 300 micrograms/kg) for 6-12 wk. Compared with euthyroid control rats (Eut, n = 27), Hyper exhibited left ventricular hypertrophy (Eut, 2.01 +/- 0.04 mg/g body wt; Hyper, 2.70 +/- 0.06; P < 0.0005) and greater oxidative enzyme activity in several skeletal muscles (all P < 0.0005). Vascular rings, 2-3 mm in axial length, were prepared from abdominal aortas, and responses to vasoactive agents were determined in vitro. Compared with Eut, vascular rings with intact endothelium from Hyper exhibited reductions in contractile responses to norepinephrine (NE) across a range of NE concentrations (P < 0.05). Maximal tension developed in response to NE was reduced approximately 30% in hyperthyroidism (Eut, 3.8 +/- 0.2 g; Hyper, 2.6 +/- 0.4; P < 0.01). Contractile responses to NE were not different between Eut and Hyper in rings denuded of endothelium. Maximal vasorelaxation responses to acetylcholine (ACh), after precontraction with NE (10(-7) M), were enhanced in the hyperthyroid state (Eut, 65.1 +/- 4.8%; Hyper, 84.0 +/- 7.1; P < 0.05). Enhanced vasorelaxation to ACh was also observed when precontraction was induced by prostaglandin F2 alpha. These findings indicate that vascular contractile and relaxation responses are altered in male hyperthyroid rats.

Acetylcholine↗

PubMed1998

Exercise training increases L-type calcium current density in coronary smooth muscle.

Exercise training produces numerous adaptations in the coronary circulation, including an increase in coronary tone, both in conduit and resistance arteries. On the basis of the importance of voltage-gated Ca2+ channels (VGCC) in regulation of vascular tone, we hypothesized that exercise training would increase VGCC current density in coronary smooth muscle. To test this hypothesis, VGCC current was compared in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 micrometer), and large arterioles (75-150 micrometer) from endurance-trained (Ex) or sedentary miniature swine (Sed). After 16-20 wk of treadmill training, VGCC current was determined using whole cell voltage-clamp techniques. In both Ex and Sed, VGCC current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit arteries. Exercise training increased peak inward currents approximately twofold in smooth muscle from all arterial sizes compared with those from Sed (large arteriole, -12.52 +/- 2.05 vs. -5.74 +/- 0.99 pA/pF; small artery, -6.20 +/- 0.97 vs. -3.18 +/- 0.44 pA/pF; and conduit arteries, -4.22 +/- 0.30 vs. -2.41 +/- 0.55 pA/pF; 10 mM Ba2+ external). Dihydropyridine sensitivity, voltage dependence, and inactivation kinetics identified this Ca2+ current to be L-type current in all arterial sizes from both Sed and Ex. Furthermore, peak VGCC current density was correlated with treadmill endurance in all arterial sizes. We conclude that smooth muscle L-type Ca2+ current density is increased within the coronary arterial bed by endurance exercise training. This increased VGCC density may provide an important mechanistic link between functional and cellular adaptations in the coronary circulation to exercise training.

Animals↗

PubMed1998

Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats.

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

Animals↗

PubMed1998

Vasoconstrictor responses of coronary resistance arteries in exercise-trained pigs.

Coronary resistance arteries isolated from exercise-trained pigs have been shown to exhibit enhanced myogenic reactivity (J. M. Muller, P. R. Myers, and M. Harold Laughlin. J. Appl. Physiol. 75: 2677-2682, 1993). The purpose of this study was to test the hypothesis that exercise training results in enhanced vasoconstrictor responses of these arteries to all vasoconstrictor stimuli [specifically acetylcholine (ACh), endothelin-1 (ET-1), KCl, and the Ca2+ channel-agonist Bay K 8644]. Female Yucatan miniature swine were trained (Trn) on a motor-driven treadmill (n = 16) or remained sedentary (Sed, n = 15) for 16-20 wk. Arteries 50-120 micron in diameter were isolated and cannulated with micropipettes, and intraluminal pressure was set at 60 cmH2O throughout experiments. Vasoreactivity was evaluated by examining constrictor responses to increasing concentrations of ACh (10(-9) to 10(-4) M), ET-1 (10(-10) to 10(-8) M), KCl (bath replacement with isotonic physiological saline solution containing 30 or 80 mM), and Bay K 8644 (10(-9) to 10(-6) M). Constricted diameters are expressed relative to the passive diameter observed after 100 microM SNP. All four constrictors produced similar decreases in diameter in arteries from both groups [ACh: 0.52 +/- 0.07 (Trn) and 0.54 +/- 0,06 (Sed); ET-1: 0.66 +/- 0.05 (Trn) and 0.70 +/- 0.07 (Sed); KCl: 0.66 +/- 0.05 (Trn) and 0.70 +/- 0.07 (Sed); Bay K 8644: 0.86 +/- 0.05 (Trn) and 0. 76 +/- 0.05 (Sed)]. Present results combined with previous observations indicate that exercise training does not alter vasoconstrictor responses of porcine coronary resistance arteries but specifically increases myogenic reactivity. Thus the underlying cellular mechanisms for myogenic tone are altered by training but not receptor-mediated mechanisms (ACh and ET-1) nor voltage-gated Ca2+ channels (KCl and Bay K 8644) in coronary resistance arteries.

Acetylcholine↗

PubMed1998

Exercise training increases K+-channel contribution to regulation of coronary arterial tone.

The present study examined whether regulation of coronary tone in conduit arteries (>1.0 mm ID) is altered by exercise training. Yucatan miniature swine were treadmill trained for 16-20 wk (Ex) and compared with sedentary counterparts (Sed). Endothelium-denuded arterial rings were stretched to optimal length and allowed to equilibrate for 60 min. Inhibition of either Ca2+-activated channels [1 mM tetraethylammonium (TEA) or 10 nM iberiotoxin (IBTX)] or voltage-dependent K+ channels [1 mM 4-aminopyridine (4-AP)] significantly increased resting tension in both groups; however, the effect of all K+-channel blockers was greater in Ex. Addition of 1 mM sodium nitroprusside reduced resting tension in both groups, confirming the presence of active basal tone; however, sodium nitroprusside-sensitive tone was increased approximately twofold in Ex compared with Sed group. Perforated patch-clamp experiments on isolated smooth muscle cells demonstrated no effect of exercise training on whole cell TEA-sensitive, 4-AP-sensitive, or basal K+ current. Similarly, whereas TEA, 4-AP, and IBTX all decreased resting membrane potential, there was no difference in depolarization between groups. The greater effect of TEA on resting tension in Ex could be mimicked in Sed by addition of the Ca2+-channel agonist BAY K 8644. In conclusion, the greater response to K+-channel blockers after exercise training is consistent with an increased contribution of K+ channels to regulation of basal tone in conduit coronary arteries. The lack of an effect of training on K+ current characteristics or membrane potential responses in isolated cells suggests that a requisite factor for enhanced K+-channel activation in arteries from Ex, possibly stretch, is absent in isolated cells.

4-Aminopyridine↗

PubMed1997

Altered basal and adenosine-mediated protein flux from coronary arterioles isolated from exercise-trained pigs.

Solute flux per unit surface area and concentration gradient, (J(S)/SdeltaC), was quantified in arterioles isolated from hearts of sedentary (SED) and exercise-trained (EX) female Yucatan Miniature Swine. Apparent permeability (P(S)) was assessed from measures of J(S)/SdeltaC for two proteins, alpha-lactalbumin (alpha-lact) and porcine serum albumin (PSA), under basal conditions and following 5 min suffusion with 10(-5) M adenosine (ADO). Both proteins were labelled with the fluorescent dye tetramethyl rhodamine isothiocyanate. Basal P(S) to alpha-lact differed with exercise training ((P(S)alpha-lact)SED = 5.2+/-1.8 (median+/-median absolute deviation (MAD), n = 9 pigs) versus (P(S)alpha-lact)EX = 7.4+/-1.1 x 10(-7) cm s(-1), n = 9, P < 0.05). For the larger protein PSA, basal P(S) did not change with training (P(S)PSA)SED = 50+/-1.6, N = 11 vs. (P(S)PSA)EX = 4.1+/-1.2 x 10(-7) cm s(-1), N = 11). Suffusion of the arterioles (33+/-4 microm diameter, n = 18 vessels) from SED hearts (n = 14) with 10(-5) M ADO decreased P(S)alpha-lact 15+/-8% relative to control and was without effect on P(S)PSA. By contrast, in arterioles (39+/-4 microm diameter, n = 22 vessels) from EX hearts (n = 14), ADO increased P(S)alpha-lact and P(S)PSA by 32 and 65% respectively, indicating that receptor-mediated changes in permeability were also sensitive to exercise training. These data demonstrate that, for coronary arterioles, permeability to macromolecules adapts to exercise training. The adaptive mechanisms may involve more than one structural component of the vessel wall as the changes in permeability were size-dependent.

Adenosine↗

PubMed1997

Exercise effect on canine and miniswine cardiac catecholamines and enkephalins.

Chronic exercise changes cardiac function and responsiveness to autonomic control. Catecholamines and enkephalins are neuroendocrine transmitters involved in autonomic regulation and signaling. We hypothesized that intermittent increased sympathetic stimulation caused by exercise training would decrease cardiac catecholamine and enkephalin content. Dogs and miniswine were exercise trained and hearts extracted for catecholamine and enkephalin measurements. Atrial catecholamine content is greater than ventricular content in dog heart which is in keeping with the greater atrial neuronal density. In contrast, porcine epinephrine content was evenly distributed across heart sections and norepinephrine content was greater on the right side than the left. Changes in miniswine and dog heart catecholamine content after exercise training were different. Canine cardiac norepinephrine content decreased and porcine norepinephrine content increased. This indicates a difference in cardiac adrenergic control in miniswine versus canines. Methionine-enkephalin (met-enk) distribution across canine heart is uniform, unlike the miniswine, where the atria contain more than the ventricles. Proenkephalin processing produces four met-enk sequences and one met-enk-arg-phe; despite this, ventricles of both species contain more met-enk-arg-phe immunoreactivity than met-enk. Therefore, proenkephalin processing is incomplete in heart tissue. Exercise training in the dog resulted in decreased cardiac met-enk, decreased left atrial met-enk-arg-phe, and increased ventricular met-enk-arg-phe. Porcine cardiac enkephalin concentration was unchanged by training. The changes in the enkephalins may be explained by changes in proenkephalin processing and/or release. Met-enk-arg-phe is particularly good at modulating vagal stimulation of the canine heart. The changes in tissue content seen after exercise training may be a result of the exercise-induced change in autonomic tone to the heart. These data suggest species dependent changes in autonomic regulation.

Analysis of Variance↗

PubMed1997

Time course of enhanced endothelium-mediated dilation in aorta of trained rats.

Previous work has demonstrated that 10 wk of exercise training enhances the responsiveness of rat abdominal aortas to acetylcholine (ACh), an endothelium-dependent vasodilator. The purpose of this study was to determine the time course for this training-induced adaptation of vascular endothelium. Additionally, the contribution of the cyclooxygenase and nitric oxide synthase mechanisms to the enhanced endothelium-mediated relaxation were examined. Male rats were divided into sedentary (SED) and exercise groups. Exercised animals were further subdivided into postexercise (POST-EX), 1 DAY, 1 WK, 2 WK, 4 WK and 10 WK groups. Exercise consisted of treadmill running at 30 m.min-1 (15 degrees incline) for 1 h.d-1 (5 d.wk-1 for the 1 WK, 2 WK, 4 WK, and 10 WK groups). Maximal vasodilator responses induced by 10(-4) M ACh (10(-7) M norepinephrine preconstriction) were determined on abdominal aortic rings in vitro immediately after a single exercise bout in POST-EX rats and 24 h after a single bout of exercise in 1 DAY animals. Maximal 10(-4) M ACh-induced dilation of aortas from 1 WK, 2 WK, 4 WK, and 10 WK animals was determined 24 h after the last exercise bout. Soleus muscle citrate synthase activity was greater in 2 WK (31 +/- 1 mumol.min-1.g wet wt-1), 4 WK (34 +/- 2), and 10 WK (36 +/- 1 mumol.min-1.g wet wt-1) rats than in SED (27 +/- 1 mumol.min-1.g wet wt.-1) animals. Maximal ACh-induced relaxation was greater in aorta from 4 WK (72 +/- 2%) and 10 WK (79 +/- 1%) rats than SED (61 +/- 2%) rats. ACh-mediated dilatory responses remained enhanced in the presence of the cyclooxygenase blocker indomethacin (10(-5) M), but were abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (300 microM). In addition, the expression of endothelial nitric oxide synthase (ecNOS) protein in aortas from 4 WK (P = 0.057) and 10 WK (P < 0.05) rats was greater than in aortas from SED animals. These data indicate that the enhanced endothelium-dependent, ACh-mediated dilation of the rat aorta is present by 4 wk of endurance exercise training. This adaptation appears to be mediated primarily through the nitric oxide synthase pathway and is associated with an increased expression of ecNOS.

Acetylcholine↗

PubMed1997

A review of effects of hypothyroidism on vascular transport in skeletal muscle during exercise.

Hypothyroidism is a common thyroid disease characterized by exercise intolerance. Both exercise capacity and endurance are compromised in the hypothyroid state. Studies involving rats performing treadmill running have shown that blood flows during exercise to high oxidative, extensor-type muscles are lower in hypothyroid rats compared with those in euthyroid rats. Abnormal cardiac and vascular function appear to contribute to this hypoperfusion. Experiments involving isolated arterial vessel segments have demonstrated that potential for constriction is normal in vessels from hypothyroid animals; however, reduced vasodilator potential is associated with hypothyroidism. Dysfunction of both endothelium and vascular smooth muscle appear to contribute to blunted potential for vasodilation. Altered ability to generate vasodilatory substances and/or changes in responses to these vasodilators may account for vascular dysfunction. It appears that impaired vascular function interacts with other factors such as poor myocardial function and changes in energy metabolism to compromise exercise tolerance.

Animals↗

PubMed1997

Heterogeneity of L-type calcium current density in coronary smooth muscle.

Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible factor may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+ current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 microm), and large arterioles (75-125 microm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased approximately 2.5- and approximately 1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (-5.58 +/- 0.53, -3.54 +/- 0.34, and -2.26 +/- 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative as -40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (-13.23 +/- 0.88, -6.22 +/- 1.35, and -8.62 +/- 0.81 mV, respectively; P < 0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

Animals↗

PubMed1997

Flow-induced dilation of rat soleus feed arteries.

Flow-induced dilation is thought to contribute to dilation of skeletal muscle arteries and arterioles during exercise hyperemia. We sought to determine whether rat soleus feed arteries (SFA) exhibit flow-induced dilation and to evaluate the potential contribution of flow-induced dilation of SFA to exercise hyperemia. Rat SFA were isolated and cannulated to allow pressure and intraluminal flow to be independently controlled. Intraluminal pressure was maintained at 90 cmH2O throughout the experiment. All SFA (n = 13) developed spontaneous tone and dilated in response to flow. Flow of 10 and 14 microliters/min produced a 34 +/- 14 and 56 +/- 17 microns increase above basal diameter (135 +/- 12 microns), respectively. Flows > 14 microliters/min produced little further dilation. Maximum flow-induced dilation was 86 +/- 3% of passive diameter determined in calcium-free physiological saline solution. Calculated shear stress was maintained at 4-6 dyn/cm2 at flows of 10-20 microliters/min but increased at greater flows because SFA did not dilate further. To determine whether dilation in response to flows in this range may contribute to exercise hyperemia, we estimated in vivo SFA blood flows from previously published soleus blood flow data. Anesthetized rats are estimated to have flows of 10 microliters/min per SFA, and conscious rats are estimated to have flows of 95 (nonexercising), 153 (walking), and 225 (running) microliters/min per SFA. Corresponding shear stresses were estimated to be 26 (anesthetized), 47 (conscious, nonexercising), 75 (walking), and 111 (running) dyn/cm2. Because estimated in vivo values for both flow and wall shear stress are far greater than the flow and/or shear stresses at which maximal flow-induced dilation occurs in vitro, we conclude that flow-induced dilation contributes little to dilation of SFA during locomotory exercise.

Animals↗

PubMed1997

Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs.

The purpose of this study was to develop a method by which endothelial cell nitric oxide synthase (ecNOS) mRNA expression could be measured in single coronary resistance arteries and to test the hypothesis that ecNOS gene expression is upregulated by exercise training. Yucatan miniature swine were randomly assigned to exercise-trained (ET; n = 5) or sedentary (Sed; n = 4) groups for 16 wk. Individual coronary resistance arteries (50-100 microns) were dissected, frozen in liquid nitrogen, and homogenized in a LiCl buffer, mRNA was isolated from each vessel, and ecNOS gene expression was assessed using reverse transcriptase (RT)-polymerase chain reaction (PCR) standardized by coamplifying ecNOS with glyceraldehyde 3-phosphate dehydrogenase (GAPHD). The ecNOS-to-GAPDH amplicon ratio was significantly greater in coronary resistance arteries isolated from ET pigs than in Sed controls. On the basis of these data, it is concluded that RT-PCR can be used on single coronary resistance arteries to assess cell-specific mRNA expression and that ecNOS gene expression is upregulated by exercise training in porcine coronary resistance arteries.

Animals↗

PubMed1997

Short-term exercise training alters responses of porcine femoral and brachial arteries.

The primary purpose of this study was to test the hypothesis that short-term exercise training enhances endothelium-dependent relaxation of porcine femoral and brachial arteries. Miniature swine ran on a treadmill for 1 h at 3.5 miles/h, twice daily, for 7 consecutive days (Trn; n = 8). Compared with sedentary controls (Sed; n = 7), Trn swine exhibited increased skeletal muscle citrate synthase activity (P < 0.05). Vascular rings approximately 3 mm in axial length were prepared from segments of femoral and brachial arteries, and responses to vasoactive agents were determined in vitro. Sensitivity to bradykinin (BK) was enhanced in brachial vascular rings from Trn swine compared with those from Sed swine, as indicated by lower concentration of vasorelaxing agent eliciting 50% of maximal response values [Sed, 8.63 +/- 0.09 (-log M); Trn, 9.07 +/- 0.13; P < 0.05]. This difference between groups was preserved in brachial rings in which formation of nitric oxide and vasodilator prostaglandins were inhibited [Sed, 8.57 +/- 0.17 (-log M); Trn, 8.97 +/- 0.13; P < 0.05]. Sensitivity to BK was not different between Sed and Trn in femoral arterial rings. Relaxation responses to the calcium ionophore A-23187 and sodium nitroprusside were not altered with training. Femoral and brachial arterial rings from Trn swine, compared with those from Sed swine, exhibited augmented vasocontraction across a range of concentrations and increased sensitivity to norepinephrine (all P < 0.05). These findings indicate that responses of porcine femoral and brachial arteries change in response to short-term training. Together with findings from previous studies involving longer term training, our data suggest that vascular adaptations may differ at different time points during long-term endurance exercise training.

Animals↗

PubMed1997

Skeletal muscle biochemical adaptations to exercise training in miniature swine.

The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16-20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 +/- 1.1 mumol.min-1.g-1; Trn, 23.9 +/- 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 +/- 6%; Trn, 10 +/- 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 +/- 2; Trn, 22 +/- 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

Adaptation, Physiological↗

PubMed1997

Contractile responsiveness of coronary arteries from exercise-trained rats.

The purpose of this study was to determine whether exercise training alters vasomotor reactivity of rat coronary arteries. In vitro isometric microvessel techniques were used to evaluate vasomotor properties of proximal left anterior artery rings (1 ring per animal) from exercise-trained rats (ET; n = 10) subjected to a 12-wk treadmill training protocol (32 m/min, 15% incline, 1 h/day, 5 days/wk) and control rats (C; n = 6) restricted to cage activity. No differences in passive length-tension characteristics or internal diameter (158 +/- 9 and 166 +/- 9 micron) were observed between vessels of C and ET rats. Concentration-response curves to K+ (5-100 mM), prostaglandin F2alpha (10(-8)-10(-4) M), and norepinephrine (10(-8)-10(-4)) were unaltered (P > 0.05) in coronary rings from ET rats compared with C rats; however, lower values of the concentration producing 50% of the maximal contractile response in rings from ET rats (P = 0.05) suggest that contractile sensitivity to norepinephrine was enhanced. Vasorelaxation responses to sodium nitroprusside (10(-9)-10(-4) M) and adenosine (10(-9)-10(-4) M) were not different (P > 0.05) between vessels of C and ET rats. However, relaxation responses to the endothelium-dependent vasodilator acetylcholine (ACh; 10(-10)-10(-4) M) were significantly blunted (P < 0.001) in coronary rings from ET animals; maximal ACh relaxation averaged 90 +/- 5 and 46 +/- 12%, respectively, in vessels of C and ET groups. In additional experiments, two coronary rings (proximal and distal) were isolated from each C (n = 7) and ET (n = 7) animal. Proximal coronary artery rings from ET animals demonstrated decreased relaxation responses to ACh; however, ACh-mediated relaxation of distal coronary rings was not different between C and ET groups. NG-monomethyl-L-arginine (inhibitor of nitric oxide synthase) blocked ACh relaxation of all rings. L-Arginine (substrate for nitric oxide synthase) did not improve the blunted ACh relaxation in proximal coronary artery rings from ET rats. These studies suggest that exercise-training selectively decreases endothelium-dependent (ACh) but not endothelium-independent (sodium nitroprusside) relaxation responses of rat proximal coronary arteries; endothelium-dependent relaxation of distal coronary arteries is unaltered by training.

Acetylcholine↗