Biomedical subjects

J M Lash

Publications and source records attributed to J M Lash.

34 records · Page 2Linked to original sources

PubMed1993

Adrenergic and pressure-dependent vascular regulation in sedentary and trained rats.

In this study, we determined if aerobic exercise training alters adrenergic or pressure-dependent vascular regulation in the rat hindlimb or intestine. Pressor responses to bilateral carotid artery occlusion and systemic phenylephrine (PE) infusion were not altered by training. During occlusion, peak and steady-state changes in hindlimb vascular resistance (HLR) were significantly greater in trained (24 and 13%) than in sedentary (8 and -3%) rats; a similar trend existed for intestinal vascular resistance (IR). The pressure-dependent contribution was consistent between groups (HLR: peak 55-85%, steady state 25-45%; IR: peak and steady state 40-65%). During PE infusion, increases in IR and HLR were similar between groups. The increase in HLR was substantially pressure dependent in both groups (approximately 50% at highest dose) as was the change in IR in trained rats. However, the IR response to PE was not pressure dependent in sedentary rats. The direct effects of PE were similar between sedentary and trained rats in the hindlimb but were suppressed in the intestine of trained rats compared with sedentary rats. Therefore, aerobic exercise training altered adrenergic and pressure-dependent vasoregulatory mechanisms in both skeletal muscle and intestinal tissues.

Animals↗

PubMed1992

Effects of downhill running on the responses to an oral glucose challenge.

Because muscle damage from eccentric exercise has been associated with alterations in muscle glycogen metabolism, this study determined the effects of exercise on the insulin and glucose responses to an oral glucose tolerance test (OGTT). In a repeated-measures design, 11 subjects undertook either no exercise, 2 min of isokinetic leg exercise, or 50 min of level or downhill running. No exercise was performed and diet was controlled during the 48 hrs after the treatments and before the OGTT. Ratings of muscle soreness and CK activity were significantly elevated 48 hrs after downhill running. Level running also increased CK activity but did not induce muscle soreness. Isokinetic exercise did not affect either one. Blood glucose responses to the OGTT were similar among the treatments. In contrast, the insulin responses to the OGTT following downhill running were significantly increased. These results suggest that eccentric exercise associated with downhill running that results in delayed muscle soreness is associated with the development of a mild insulin-resistant condition.

Adult↗

PubMed1992

Intestinal lymphatic vessels release endothelial-dependent vasodilators.

This study evaluated the possibility that the endothelial cells of microscopic lymphatic vessels can release vasoactive agents which affect the lymphatic vessels and nearby arterioles. Microinotophoresis of acetylcholine (ACh) or bradykinin (BK) onto the wall of quiescent submucosal lymphatic vessels in the rat small intestine had no discernible effects on their diameters but caused spontaneously active mesenteric lymphatic vessels to constrict. Application of ACh or BK to the arteriolar wall caused significant vasodilation. Release of either drug onto the wall of a nearby lymphatic produced arteriolar dilation that was approximately 80% of that observed with direct application to the arteriolar wall; drug application into parenchymal tissue produced a dilation less than 25% of that observed during application to the lymphatic. NG-monomethyl-L-arginine application to the lymphatic blocked all ACh-induced lymphatic-mediated responses but had no effect on the response to direct ACh application to the arteriolar wall or any of the responses to BK application. These results are consistent with the hypothesis that lymphatic endothelial cells are capable of releasing agents that dilate nearby arterioles and cause spontaneously active lymphatic vessels to constrict.

Acetylcholine↗

PubMed1992

Systemic responses to carotid occlusion in the anesthetized rat.

We evaluated the effects of four standard anesthetization regimens on the systemic cardiovascular responses to bilateral common carotid artery occlusion in 28 adult male rats. Rats were randomly assigned to anesthesia groups: thiopental sodium (PT; 100 mg/kg ip), alpha-chloralose (CH; 100 mg/kg iv), ketamine hydrochloride plus acepromazine (KA; 135 mg/kg and 1.5 mg/kg sc), and pentobarbital sodium (PB; 50 mg/kg ip). PT and PB animals had similar baseline heart rates (HR; 333 and 345 beats/min, respectively) and arterial pressures (MAP; 126 and 118 mmHg, respectively), whereas both were lower in CH and KA (314 and 288 beats/min, 92 and 85 mmHg). During bilateral carotid occlusion, PT demonstrated the largest change in MAP (dMAP; +27 mmHg) but the smallest change in HR (dHR; +8 beats/min). CH and PB demonstrated similar dHR (+24 and +16 beats/min) and dMAP (+20 and +19 mmHg). KA demonstrated a significant dHR (+14 beats/min), but the average dMAP was not statistically significant (+3 mmHg). Therefore, carotid occlusion in rats anesthetized with PT, PB, or CH consistently elicits a systemic arterial pressor response comparable with that reported for conscious animals. When the magnitude and stability of baseline HR and MAP are also considered, PT and PB anesthetization seem to be the most reliable for evaluation of the carotid occlusion pressor response in rats.

Anesthetics↗

PubMed1992

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.

Adaptation, Physiological↗

PubMed1991

New technique to completely isolate carotid sinus baroreceptor regions in rats.

We developed a method by which we can completely isolate the carotid sinus baroreceptor regions in the rat. The carotid sinus baroreceptor region is exposed and, with the use of extra-fine forceps, a human hair is placed around and tied at the root of the bifurcation. This procedure occludes the external carotid artery and blood flow to the carotid body. An injector is then attached to a catheter in the common carotid artery. We introduce a cylindrical rubber plug into either the palentine or internal carotid artery. A second plug is introduced to occlude the other artery. In six of the eight rats studied, these procedures completely isolated the carotid sinus region. In those cases where a small leak persisted at a carotid sinus pressure of 180 mmHg, we introduced a small particle of the animal's own previously clotted blood. Carotid sinus pressure was either randomly changed between 40 and 180 mmHg in 20-mmHg increments or in sequential 20-mmHg steps from 40 to 180 mmHg while measuring the animal's pulsatile and mean blood pressures. Arterial pressure-carotid sinus pressure relationship indicates that there is a highly sigmoidal relationship between the two pressures. The peak gain of the carotid sinus reflex system had a range from 1.5 to 4.0 and a mean value of 2.07 +/- 0.08. Our data indicate that the rat exhibits a significant carotid sinus baroreceptor reflex response. This technique combined with other techniques will allow for the study of neural control of cardiovascular function in the rat.

Animals↗

PubMed1991

Mechanical characteristics and active tension generation in rat intestinal arterioles.

The contributions of active and passive wall tension to regulation of arteriolar diameters were determined for large (1A), intermediate (2A), and small (3A) arterioles in the small intestine of the anesthetized rat. Active tension (Ta) contributed greater than 85% of total wall force at rest in 2A and 3A and 75-80% of total force in 1A. Ta was approximately 90% of peak active tension (Ta,peak) for large through small arterioles, even though absolute Ta varied by fourfold. A linear relationship between microvascular pressure and Ta was observed for decreases in pressure in all arterioles. Ta remained nearly constant for pressure increases of 40% in 2A and 3A but was increased in 1A. Because of the plateau of the circumference-Ta relationship near Ta,peak, superfusion of progressively increasing concentrations of norepinephrine or adenosine resulted in maintenance of the close Ta-Ta,peak relationship unless the vessel diameter changed greater than 25%. These results indicate that, while arteriolar diameters vary substantially, near-peak Ta is generated for a variety of physiological conditions.

Adenosine↗

PubMed1991

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.

Animals↗

PubMed1991

Structural and functional origins of suppressed acetylcholine vasodilation in diabetic rat intestinal arterioles.

This study evaluated the possible impairments to endothelium-mediated vasodilation by structural and functional properties of the intestinal arterioles in adult (20-21-week-old) rats after 8-11 days or 7-8 weeks of streptozotocin-induced diabetes. Arteriolar intravascular pressures and luminal diameters were simultaneously measured during iontophoretic application of acetylcholine, bradykinin, and nitroprusside to the outer vessel wall, and passive diameter-pressure relations were obtained during maximal vasodilation. Microvascular pressures and circumference-passive wall tension relations were similar between all diabetic and normal rats and did not appear to significantly influence vasodilation. Both acute and chronic hyperglycemia were associated with near complete suppression of acetylcholine-induced vasodilation in large arterioles, and the threshold dose for vasodilation of intermediate arterioles was approximately 10-fold higher in diabetic rats. In both diabetic groups, dilatory responses to nitroprusside were normal, and in chronically diabetic rats, the relative vasodilation in response to various doses of bradykinin was equivalent to that found in normal rats. These observations indicate that a very specific deficit of acetylcholine-induced endothelium-derived relaxing factor action rapidly develops in intestinal arterioles of diabetic rats, but the arteriolar wall mechanical properties, cGMP-mediated muscle relaxation, and endothelial release of the bradykinin-stimulated relaxing factor are not compromised after 7-8 weeks of chronic hyperglycemia.

Acetylcholine↗

PubMed1991

Hemodynamic effects of varied graft diameters in the venous system.

Both in vivo and mathematical models of venous hypertension were used to evaluate the hemodynamic effects of 4, 6, 8, and 10 mm diameter cross-femoral venous bypass grafts (CFBs). Eighteen grafts (length 138 +/- 3.4 mm) were tested in paired sequential fashion (four grafts, 4 and 8 mm; five grafts, 6 and 10 mm) in nine greyhounds (femoral vein diameter, 7.7 +/- 0.09 mm). Bilateral hindlimb venous pressures and flows were measured before and after unilateral iliofemoral venous ligation, 30 minutes after CFB insertion, and for 5 minutes after venous flow augmentation induced by stimulated muscle contraction. CFBs of all sizes were equally effective at relieving the occlusive venous hypertension at rest. Muscle contraction elevated venous pressure in all ligated hindlimbs (p less than 0.0001); however, the pressure returned to baseline by 3 minutes in dogs with 6, 8, and 10 mm grafts but remained elevated (p less than 0.05) with the 4 mm grafts even after 5 minutes. Peak graft flow (first 90 seconds after contraction) was significantly greater through the 8 mm grafts than through the 4 mm grafts (p less than 0.01), although no difference was noted in flow rates between 6 and 10 mm grafts. The pressure gradient across the graft as predicted by the mathematic model for 6 to 10 mm conduits was less than 5 mm Hg for flows up to 1000 ml/min, although the pressure gradient of the 4 mm graft exceeded 5 mm Hg at 200 ml/min and approached 30 mm Hg at 1000 ml/min. Therefore, data from both canine and mathematical models agreed that, at rates approximating human resting flow (1000 ml/min), no adverse short-term hemodynamic consequences result from CFB conduits of 6 to 10 mm diameter.

Animals↗

PubMed1991

Inadequacy of saphenous vein grafts for cross-femoral venous bypass.

A mathematic model of unilateral iliac vein obstruction was used to establish the theoretic basis for selecting saphenous vein or a larger diameter prosthetic cross-femoral venous bypass graft for relief of obstructive venous hypertension. Common femoral vein resting and postexercise peak flows, and common femoral vein and saphenous vein diameters were measured in 18 healthy individuals and used to estimate the pressure gradient (dP) across 20 cm long cross-femoral venous bypass grafts of saphenous vein or 4, 6, 8, 10, and 12 mm prosthetic conduits, in the presence of a transpelvic venous collateral network of varied cross section. The upper limits of normal for the gradients in our model (dPstd) were set at 4 mm Hg for resting flows and 6 mm Hg after exercise. Mean saphenous vein diameter was 4.3 +/- 0.22 mm, which was 36.5% +/- 1.73% of common femoral vein diameter. When the saphenous veins of two thirds of the individuals in our study were used as theoretic cross-femoral venous bypass conduits, greater than 80% of postobstruction peak cross-femoral venous bypass graft flow had to be carried by collaterals to maintain a gradient less than or equal to dPstd. We demonstrated that 4.5 to 6.0 mm diameter saphenous cross-femoral venous bypass grafts would be hemodynamically efficacious in relieving venous hypertension, but only when implanted in parallel with an existing venous collateral network that limited the preoperative dP to 4.5 to 7.5 mm Hg at resting flows and 7.0 to 11.5 mm Hg after exercise; only 44% of saphenous veins were adequate for cross-femoral venous bypass grafts by these criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Maturation of the rat intestinal microvasculature from juvenile to early adult life.

The same region of intestinal ileum was compared in the same rats at 10 and 20 wk of age to determine if reported differences in vessel density between these ages were the result of changes in vessel numbers. The number and branching pattern of arterioles observed remained remarkably constant during the 10 wk between observations, and minimal enlargement of bowel mass occurred. No significant change in average maximum diameter of arterioles was observed. Although the total number of small arterioles did not change, vessels were gained and lost at an equal rate (7%) between 10 and 20 wk. There was no significant changes in means or frequency distributions of intercapillary distances in the radial or longitudinal bowel muscle layers. The results indicate that the intestinal microvascular branching pattern changes very little from juvenile to adult life. However, a slow turnover of small arterioles does occur, indicating an ongoing remodeling of the terminal vasculature during juvenile life.

Aging↗

PubMed1990

Exercise alters cardiac myosin isozyme distribution in obese Zucker and Wistar rats.

Recent evidence suggests that exercise training may significantly increase the expression of the cardiac myosin isozyme V1 in the diabetic heart, a change associated with improved cardiac functional capacity. To test this hypothesis, cardiac myofibrillar adenosinetriphosphatase (ATPase) activity and myosin isozyme profiles were determined in trained and sedentary male hyperinsulinemic obese Zucker (OZT, OZS) and obese Wistar (OWT, OWS) rats. Lean sedentary (LZS, LWS) animals served as age-matched controls. Myofibrillar ATPase activity and the relative quantity of the high-ATPase isozyme V1 was significantly lower in both strains of sedentary obese rats than in the respective lean sedentary controls (P less than 0.05). Both 5 (OZT) and 10 wk (OWT) of moderate treadmill training increased these markers of cardiac myosin biochemistry in the obese animals (P less than 0.05). Thus, endurance exercise training remodels the cardiac isomyosin profile of hyperinsulinemic rats and, in doing so, may enhance cardiac contractility and functional capacity. Such changes may reflect an improvement in glucose availability and utilization in these hearts.

Animals↗

PubMed1989

Capillary basement membrane thickness and capillary density in sedentary and trained obese Zucker rats.

The purpose of this study was to determine whether the obese Zucker rat (OZR) develops diabeteslike peripheral vascular disease and evaluate the effects of exercise training (treadmill running, 15 m/min, 17% grade, 60 min/day, 5 days/wk, for 6 or 12 wk) on skeletal muscle vascular disease. Capillary density (CD) and capillary basement membrane (CBM) thickness were measured in the plantar muscle of sedentary and trained OZR and sedentary lean Zucker rats (LZRs). At 11 wk old, when profoundly obese, hyperinsulinemic, and insulin resistant, OZRs had lower CD and thicker CBM than LZRs. These characteristics are consistent with the expression of human diabetic microangiopathy and imply altered diffusion capacity due to increased diffusion distance and changes in the capillary wall. Between 11 and 18 wk of age, OZRs became hyperglycemic. No age-related changes in CD were observed in lean or obese animals, and OZRs had lower CDs than LZRs at 18 wk of age. CBM thickness decreased from 11 to 18 wk of age in both lean and obese animals, but the decline was proportionally greater in OZRs, and the CBM of obese animals was only slightly thicker than in lean 18-wk-old animals. Exercise training did not alter CD or CBM thickness in 11-wk-old animals. In contrast, training for 6 or 12 wk increased both CD and CBM thickness in 18-wk-old animals, normalizing CD but further increasing CBM thickness relative to LZRs. Correlational analysis revealed that CBM thickness is related to basal insulin concentration (r = .29, P less than .05) but not to basal glucose (r = .12, P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Training-induced vascular and metabolic adaptations in normo(11 week)- and hyper(18 week)-glycemic obese Zucker rats.

The purpose of this study was to investigate the peripheral vascular and metabolic adaptations induced by aerobic training in normoglycemic (11-week-old) and hyperglycemic (18-week-old) insulin-resistant male obese Zucker rats (OZR). OZR were treadmill trained 6-11 (T6-11), 11-18 (T11-18), or 6-18 (T6-18) weeks of age at 15 m/min. 17 percent grade, 1 hour/day, 5 days/week. Forty-eight hours after the last training session and after a 12 hour fast, a tail vein blood sample was obtained for analysis of glucose and insulin concentrations, cholesterol, and glycosylated hemoglobin fraction. Glucose uptake and hindlimb vascular resistance were measured during extracorporeal perfusion of the hindlimb (1.0mU insulin/ml). Trained animals were compared to sedentary age-matched obese (S-OZR) and lean (LZR) animals. S-OZR were hyperinsulinemic and obese at 6 weeks of age, mildly hypercholesterolemic and hyperglycemic at 11 weeks, and profoundly hyperglycemic at 18 weeks. Training did not affect body weight or serum cholesterol. Fasting insulin and glucose concentrations were not different between sedentary and trained OZR, except T6-18 which had higher insulin and lower glucose concentrations. The insulin/glucose ratio was lower in OZR animals and was not altered by 6-7 week training (T6-11, T11-18), but was normalized by 12 week training (T6-18). No significant differences in glycosylated hemoglobin fractions were observed between groups. Normalization of glucose uptake was observed in trained 11-week-old OZR, and a statistically non-significant (P = 0.10) 40 percent improvement was observed in trained 18-week-old OZR. Hindlimb vascular resistance was elevated in the S-OZR, relative to LZR, at 11 and 18 weeks of age, and was reduced with training. One hour/day exercise training normalized hindlimb vascular resistance and glucose uptake in 11-week-old OZR, but only moderately improves these vascular and metabolic variables in 18-week-old hyperglycemic animals. Prolonged (12 weeks) training reduced the severity of fasting hyperglycemia in older animals, but at the expense of an increased fasting insulin concentration.

Adaptation, Physiological↗

PubMed1987

Perivascular and tissue PO2 in contracting rat spinotrapezius muscle.

This study evaluated the possibility that during skeletal muscle contractions tissue O2 tension (Po2) around arterioles and venules decreases substantially more than in the middle of the capillary bed and thereby influences functional hyperemia. Periarteriolar [H+] and [K+] were also measured because most large arterioles are in close proximity to venules such that the biochemical status of the periarteriolar tissue could be influenced by a large decrease in O2 availability in the annulet of tissue surrounding the venules. Stimulation frequencies in the range of 2-12 Hz were used to activate the rat spinotrapezius muscle. Periarteriolar and capillary bed Po2, [H+], and [K+] changed during the first few minutes of stimulation but were restored to near resting concentrations as the functional hyperemia developed. However, perivenular Po2 decreased rapidly to approximately 50-60% of the resting gas tension as contractions began, and only minor recovery occurred. Elevation of tissue and periarteriolar Po2 with an O2-enriched superfusion solution did not prevent dilation during contractions to the same diameter as during the response at very low superfusion Po2. Therefore, the extent to which O2 influences arteriolar dilation and exercise hyperemia in the spinotrapezius muscle of the rat may depend less on periarteriolar and capillary bed Po2 than on the release of vasoactive materials from the nearby perivenular tissues as the availability of O2 decreases.

Animals↗