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Biomedical subjects

N L Stephens

Publications and source records attributed to N L Stephens.

At least 91 records · Page 5Linked to original sources
PubMed1987

Prolonged isobaric relaxation time in small mesenteric arteries of the spontaneously hypertensive rat.

Prolonged isometric relaxation in hypertensive aortic and caudal arterial smooth muscle has been demonstrated; however, isobaric relaxation in resistance arteries is more pertinent to studies in hypertension. A comparative study of mesenteric arterial isobaric relaxation times was made using spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and MK-421 treated SHR (treatment commenced at 8 weeks of age and was maintained until sacrifice). Relaxation rates of vessels constricting against a range of pressures and achieving different degrees of narrowing or changes in circumference were analyzed. Comparisons were made between SHR, WKY, and MK-421 treated SHR arteries that had constricted from the same initial circumference and against the same magnitude of pressure. The SHR mesenteric arteries relaxed at a slower rate than did the WKY vessels. The normotensive MK-421 treated SHR showed the same prolonged relaxation rate as did the untreated SHR preparations. Thus the slower rate of relaxation in SHR arteries does not appear to be a consequence of the hypertension. Such prolonged time for narrowing would function to increase the average peripheral resistance and thus may contribute to the initiation and maintenance of increased blood pressure.

Animals↗
PubMed1987

Time dependence of series elasticity in tracheal smooth muscle.

The stress-strain curve for the series elastic component (SEC) of tracheal smooth muscle was obtained by quick releasing the muscle from isometric tension to various afterloads and measuring the elastic recoils (SEC lengths) at a specific time after stimulation. A family of such curves was obtained by releasing the muscle at different points in time during contraction. Stiffnesses of the SEC (slopes of the stress-strain curves) at a specific stress level calculated from these curves (constant-stress stiffness) showed significant difference from one another. The same difference can also be characterized by the slope of the linear stiffness-stress curve, the constant A. The constant A during a 10-s isometric contraction was maximal at 2 s. It then decreased with time. This stiffness behavior is only seen when the effect of stress is held constant or eliminated. If stress is allowed to increase with time as it does during a tetanus then stiffness appears to increase monotonically. The SEC stiffness during active contraction was found to vary within the boundaries of the stiffness of muscle in rigor (upper limit) and that at resting state (lower limit).

Animals↗
PubMed1987

Mechanical properties of vascular smooth muscle in hypertension.

Reports from several laboratories indicate that the early part of smooth muscle contraction is achieved by normally cycling crossbridges, while the later part is subserved by slowly cycling or latch-bridges. We have recently found that the early bridges are responsible for almost 75% of the maximum shortening of the muscle. The latch bridges appear to be responsible for force production. The earliest change in the mechanical properties of caudal arteries from spontaneously hypertensive rats (SHR) is an increase in maximum shortening ability (delta Lmax), at a time when there is no detectable change in maximal isometric tetanic tension (Po). This substantiates the hypothesis that changes in Po are late indices of disease. The increased delta Lmax is associated with increased maximal velocity of shortening (Vo) of early cross-bridges, whereas latch bridge activity is normal. This provides the first subcellular explanation for the increase in delta Lmax. Since hypertension must result from narrowing of blood vessels, delta Lmax is, parenthetically, the important variable to study. Changes in Po, while contributing to increased vascular wall stiffness, do not directly account for the increased resistance. The cause of the increased cycling rate of crossbridges is probably increased myosin ATPase activity, or myosin light-chain phosphorylation by the specific kinase. Studies in helical sections of caudal, and segments of mesenteric resistance arteries provided similar results, confirming the suitability of caudal arteries as a model of resistance vascular units. The larger vessel is of course much easier to work with.

Aging↗
PubMed1987

Local parasympathetic mechanisms for ragweed-sensitized canine trachealis hyperresponsiveness.

Previous studies from our laboratory showed an atropine-sensitive component in the hyperresponsiveness of ragweed-sensitized canine tracheal smooth muscle (TSM) in vitro to histamine and potassium. The present studies were undertaken to elucidate the nature of the parasympathetic element in this hyperresponsiveness. TSM strips were dissected from ragweed-sensitized and littermate control dogs and their isometric force generation was measured in vitro. Mechanical responses of sensitized TSM were characterized by hyperreactivity (upward shift of the dose-response relationship) to acetylcholine (ACh), atropine-sensitive spontaneous base line activity and prolonged isometric force plateaus. Control TSM did not contract spontaneously and basal tone was maintained passively. However, eserine could produce spontaneous base-line activity and prolonged isometric force plateau in control TSM that mimicked that observed naturally in sensitized TSM. Sensitized TSM was supersensitive (leftward shift of the dose-response relationship) to ACh and electrical field stimulation, and showed a significant leftward shift of the threshold dose to carbamylcholine (carbachol). However, sensitized and control TSMs were equally reactive to carbachol at doses of 10(-8) M and greater. Also, ACh dose-response curves of sensitized and control TSMs in the presence of the cholinesterase inhibitor eserine (10(-8) M) showed no significant differences in sensitivity or reactivity. These results were consistent with a role for local parasympathetic mechanisms such as altered ACh release and/or breakdown in the hyperresponsiveness of ragweed-sensitized canine TSM.

Acetylcholine↗
PubMed1986

Decreased velocity of shortening in arterial smooth muscle from older (28- to 31-week-old) spontaneously hypertensive rats.

An increased maximum velocity of shortening (Vmax) and increased shortening ability (delta Lmax) have been reported for caudal arterial smooth muscle from 16- to 18-week-old spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) control rats. It is known that hypertension results in hypertrophy of vascular smooth muscle. It is plausible that the faster Vmax of 16- to 18-week-old SHR arterial smooth muscle may slow down with age due to hypertrophy. The force-velocity (F-V) study done previously on caudal arterial strips from 16- to 18-week-old SHR and WKY rats was repeated on preparations from 28- to 31-week-old rats. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed that the 28- to 31-week-old SHR (n = 7) mean F-V curve was not different from the 28- to 31-week-old WKY (n = 5) mean F-V curve (p greater than 0.05), and the shortening ability of 28- to 31-week-old SHR arterial muscle was significantly depressed compared with 28- to 31-week-old WKY arterial muscle (p less than 0.01). In conclusion, (i) although Vmax is faster in younger (16- to 18-week-old) SHR compared with age-matched WKY caudal arterial smooth muscle, SHR Vmax is not different from WKY Vmax in the older (28- to 31-week-old) rats. (ii) Shortening ability is greater in 16- to 18-week-old SHR caudal arterial strips compared with 16- to 18-week-old WKY strips, but is significantly depressed in 28- to 31-week-old SHR compared with 28- to 31-week-old WKY preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Force-velocity curves for smooth muscle: analysis of internal factors reducing velocity.

In tracheal smooth muscle, we obtained quantitatively different force-velocity (F-V) curves at early (2 s) and late (8 s) stages of an isometric tetanus whose contraction time was 12 s. These were essentially two samples from a continuum of F-V curves operating between 0 and 12 s. The cross-bridge cycling velocity at 8 s was slower and less sensitive to external load change compared with that at 2 s. This is possibly due to the presence of two types of cross bridges with different F-V characteristics; at 2 s most of the bridges resemble a cycling type, whereas at 8 s there is a population of what Dillon et al. have called slowly cycling or latch type interactions. Another possibility is that, due to some intrinsic factors, the whole population of cross bridges gradually change their F-V characteristics. Functions a(t) and b(t) were obtained by applying load clamps at 1-s intervals throughout a tetanus (a and b are asymptote values derived from the F-V hyperbolic curves): a increased with time, b remained constant. Analysis suggested that a/b was a valid index of internal factors that affect shortening velocity of unloaded muscle, and it is progressively increased in value during contraction.

Animals↗
PubMed1986

Time dependence of shortening velocity in tracheal smooth muscle.

It seems fairly well established that in the early phase of smooth muscle contraction cross bridges cycle at a relatively rapid rate. Later on these are replaced by very slowly cycling cross bridges or "latch bridges," operating with high economy. We describe a method to identify the time at which the transition occurs. By abruptly applying a light afterload at varying time intervals after stimulation of a canine tracheal smooth muscle, a point in time could be identified when cross-bridge cycling slowed. This was called the transition time. Because this transition was load dependent, the study was repeated with the preload abruptly reduced to zero. This permitted analysis of data in terms of cross-bridge activity. Maximum zero load velocity (Vo) of the contractile machinery was plotted against time and yielded a biphasic curve. The descending limb of the curve was fitted by a curve of the form Vo(t) = alpha e-K1t + beta e-K2t; K1 was almost three times greater than K2. We speculate that the faster rate constant represented activity of the early rapidly cycling cross bridges, and the slower constant reflected cycling rates in the latch state. These results are consistent with the latch bridge hypothesis put forward by Dillon et al. and enable us to provide a first approximation of the relative velocities of the two types of cross bridges.

Animals↗
PubMed1986

Studies of myofibrillar ATPase in ragweed-sensitized canine pulmonary smooth muscle.

The maximal shortening velocities of tracheal and pulmonary vascular smooth muscle from ragweed-sensitized dogs were significantly higher than those of muscles from their littermate controls. Myofibrils of tracheal and pulmonary vascular smooth muscle from ragweed-sensitized and control dogs were obtained with use of Triton X-100 homogenizing solution. The myofibrillar adenosinetriphosphatase (ATPase) activities of the sensitized tissues were significantly higher (P less than 0.05) than those of their respective controls.

Adenosine Triphosphatases↗
PubMed1986

Changes in cross-bridge properties of sensitized airway smooth muscle.

We have reported previously that in ovalbumin-sensitized canine tracheal smooth muscle (TSM) the maximum ability to shorten is increased. This could account for the increased airway narrowing seen in vivo in allergic bronchoconstriction. It was associated with increased velocity of shortening. We now report that, by using an electromagnetic muscle lever system, quick releases were applied to control and sensitized TSM at 0.5-s intervals throughout the course of a lightly preloaded 10-s isotonic contraction. From the records obtained it is possible to determine that, early in contraction, shortening is brought about by relatively rapidly cycling [0.35 optimal muscle length units +/- 0.033/s (SE)] cross bridges. We also report that in the sensitized TSM it is the early bridges that increase their velocity by 26.6% (P less than 0.05) compared with similar bridges in muscles from control animals. Since 70% of the maximum shortening of the muscle occurs when early bridges are operative, it is likely that these bridges are responsible for the major part of the shortening. It is thus probable that increased allergic bronchoconstriction is produced by increased activity of early, rapidly cycling bridges. The bridges that are active late in the shortening show no difference between control and sensitized airway smooth muscles.

Animals↗
PubMed1986

Effect of atropine on the hyperresponsiveness of ragweed-sensitized canine tracheal smooth muscle.

The present studies were undertaken to obtain histamine (HIST) dose-response curves for tracheal smooth muscle (TSM) from an actively ragweed-sensitized canine model of asthma and to compare these results with 1) HIST dose-response data from littermate control dogs, 2) initially nonsensitized TSM passively sensitized (in vitro) to ragweed and 3) the dose-response curve to an agonist that opens primarily voltage-sensitive calcium channels, i.e., K+. Actively ragweed-sensitized TSM was significantly hyperreactive (upward shift of the dose-response curve) to HIST (1.882 kg of force produced normalized to cross-sectional area-kg/cm2 +/- 0.087 S.E. vs. littermate controls 1.151 +/- 0.253) and hypersensitive as indicated by the leftward shift in the median effective dose or ED50 (1.86 X 10(-6) +/- 0.24 vs. 5.54 X 10(-6) +/- 1.35 M). Passively sensitized TSM (using serum from ragweed-sensitized dogs) also showed a hyperreactivity to HIST when compared to control TSM incubated with control serum (1.204 +/- 0.127 vs. 0.825 +/- 0.081 kg/cm2). No significant difference was found in the ED50 values, indicating similar sensitivities. Atropine (10(-7) M) reduced the hypersensitivity of actively sensitized TSM significantly toward control values; however, the hyperreactivity persisted. Atropine did not affect responses to HIST in control TSM. Ragweed actively sensitized TSMs were also hyperreactive and hypersensitive to K+ when compared to littermate control TSM. Atropine abolished both the hyperreactivity and hypersensitivity to K+ but had no effect on the dose-response curve of control TSM to K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Force-velocity constants in smooth muscle: afterloaded isotonic and quick-release methods.

In using pharmacologic stimuli, force-velocity (FV) curves are usually obtained by the method of quick release (QR) and redevelopment of shortening at peak tetanic tension; the advantage of the method being that the active state is at maximum. However, the QR may itself reduce the intensity of the active state and result in reduced values of FV constants. We tested this by delineating FV curves in canine tracheal smooth muscle using both conventional afterloaded isotonic contractions (ALI), and redevelopment of shortening after QR methods. For both these studies a supramaximal tetanizing electrical stimulus was used. The analysis of 11 experiments revealed that the latter method resulted in statistically significant reductions of all FV constants except for Po (maximum isometric tetanic tension). The means and standard errors for the sets of constants for the ALI and QR, respectively, are as follows: Vmax (maximum velocity of shortening) = 0.275 lo (optimal muscle length)/s +/- 0.024 (SE), and 0.216 lo/s + 0.023; a (hyperbolic constant with units of force) = 294 g/cm2 +/- 35 and 236 g/cm2 +/- 32; b (hyperbolic constant with units of velocity) = 0.059 lo +/- 0.004 and 0.039 lo/s +/- 0.005; a/Po = 0.214 +/- 0.028 and 0.182 +/- 0.026; and Po = 1.362 kg/cm2 +/- 0.106 and 1.294 kg/cm2 +/- 0.097. These data clearly show that the quick-release method for measuring force-velocity relationships in canine smooth muscle results in significant underestimates of muscle shortening properties.

Animals↗
PubMed1985

Mechanics of caudal artery relaxation in control and hypertensive rats.

Alterations of smooth muscle function can just as easily stem from mechanical alterations in its ability to relax as from alteration in contraction. Since a failure of arterial smooth muscle to relax may contribute to the development of hypertension, we felt it necessary to study the relaxation process in greater depth. The effect of load on the time course of relaxation of rat caudal artery smooth muscle was analyzed either by comparing afterloaded contractions against various loads or by imposing abrupt alterations in load. Unlike mammalian striated muscles in which relaxation was reported sensitive to loading conditions, relaxation in the smooth muscle of the rat caudal artery (n = 17) was found to be largely independent of loading conditions. This type of relaxation has been termed "inactivation-dependent" relaxation; it is typical of muscle tissue in which the calcium sequestering apparatus is poorly developed. Our results suggest that calcium resequestration, or some biochemical process downstream to it, is the rate-limiting step during relaxation in arterial smooth muscle and that this is not qualitatively different for hypertensive arterial smooth muscle. These analytic techniques were used in the study of relaxation of hypertensive vessels. Quantitative analysis of the relaxation curves showed that both isometric and isotonic relaxation time was prolonged in hypertensive arterial smooth muscle. Prolonged isotonic relaxation indicates that hypertensive arteries remain narrowed for prolonged periods compared with normotensive vessels. Such narrowed vessels may be a factor in the increased total peripheral resistance seen in genetic hypertension.

Animals↗
PubMed1985

Force-velocity relationships in hypertensive arterial smooth muscle.

Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the force-velocity (F-V) relationship in hypertensive arterial smooth muscle. Increased shortening in arterial smooth muscle would result in greater narrowing of arteries. The objectives of this investigation were to see if there is (i) increased shortening or increased maximum change in muscle length (delta Lmax where L stands for muscle length), (ii) an increased maximum velocity of shortening (Vmax) measured in l omicron per second where l omicron is the optimal muscle length for tension development, and (iii) a difference in maximum isometric tension (P omicron) developed in spontaneously hypertensive rat (SHR; N = 6) compared with normotensive Wistar Kyoto rat (WKY;N = 5) caudal artery strips. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed the following: (a) the SHR mean P omicron of 6.21 +/- 1.01 N/cm2 was not different from the mean WKY P omicron of 6.97 +/- 1.64 N/cm2 (p greater than 0.05); (b) the SHR preparations showed greater shortening for all loads imposed; (c) the SHR Vmax of 0.016 l omicron/s was greater than the WKY Vmax of 0.013 l omicron/s (p less than 0.05). This study provides evidence that while hypertensive arterial smooth muscle is not able to produce more force than normotensive arterial smooth muscle, it is capable of faster and greater shortening. The latter could result in increased narrowing of hypertensive arteries and increased blood pressure.

Animals↗
PubMed1985

Tension-velocity relationships in hypertensive mesenteric resistance arteries.

Increased total peripheral resistance is the cardinal haemodynamic disorder in essential hypertension. This could be secondary to alterations in the mechanical properties of vascular smooth muscle. Adequate study has not been made of the tension-velocity (T-V) relationship in hypertensive resistance arterial smooth muscle. Increased narrowing in such arteries would result in increased resistance. The objectives of this investigation were to determine whether there is (i) increased narrowing capacity (-delta C/C omicron, where C stands for arterial internal circumference and C omicron is the optimal arterial internal circumference for maximum tension development); (ii) an increased maximum velocity of isobaric narrowing (Vmax) measured in C omicron per second; (iii) an increased wall thickness (h); and (iv) an increased active stress development (Tmax) in the spontaneously hypertensive rat (SHR; n = 5) compared with the normotensive Wistar Kyoto (WKY; n = 5) and MK-421 (an angiotensin I converting enzyme inhibitor) treated spontaneously hypertensive rat (MK-421 trt. SHR; n = 5) mesenteric resistance (diameter, less than 300 micron) arteries. Analysis of the data for arteries constricting isobarically against a range of pressures revealed that (a) the SHR -deltaC/C omicron values at pressures ranging from 20 to 120 mmHg (1 mmHg = 133.322 Pa) showed significantly increased narrowing compared with the MK-421 trt. SHR and WKY -deltaC/C omicron values in this same pressure range (p less than 0.01), and (b) the SHR derived Vmax of 0.83 +/- 0.08 C omicron/s was significantly faster than either the MK-421 trt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗