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J Appl Physiol 88: 1199-1206, 2000;
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Vol. 88, Issue 4, 1199-1206, April 2000

Rat small mesenteric artery function after hindlimb suspension

R. C. Looft-Wilson and C. V. Gisolfi

Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

To determine whether simulated microgravity in rats is associated with vascular dysfunction, we measured responses of isolated, pressurized mesenteric resistance artery segments (157- to 388-µm ID) to vasoconstrictors, pressure, and shear stress after 28-day hindlimb suspension (HS). Results indicated no differences between HS and control (C) groups in 1) sensitivity or maximal responses to vasoconstrictors (norepinephrine, phenylephrine, serotonin, KCl); 2) ID, external diameter, or ratio of wall thickness to ID; 3) distensibility; or 4) vasodilatory responses to shear stress. Myogenic tone was attenuated (P < 0.05) in HS arteries vs. C, as evidenced by 1) decreased magnitude of tone in larger vessels (second-order branch off superior mesenteric artery, 261- to 388-µm ID) at pressures >= 40 mmHg in the presence of phenylephrine (10-7 M) and 2) decreased magnitude of tone in smaller vessels (third-order branch off superior mesenteric artery, 157- to 277-µm ID), which exhibited spontaneous tone, at pressures >= 70 mmHg. This attenuation of myogenic tone after HS could contribute to orthostatic intolerance because myogenic tone contributes to the overall tone of resistance arteries.

isolated vessels; pressure myograph; myogenic tone; shear stress; vasoconstriction


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

AFTER SPACEFLIGHT, ASTRONAUTS commonly experience orthostatic intolerance (the inability to maintain blood pressure while standing). This condition has been attributed to the inability to adequately increase peripheral vascular resistance (4, 27, 39). This could be due to depressed sympathetic stimulation of the vasculature. Evidence for this hypothesis in humans is conflicting (13, 14, 20, 39); however, there is evidence of decreased baroreflex-mediated lumbar and renal sympathetic nerve activity in rats after simulated microgravity (27). This study and others used the widely accepted hindlimb suspension model (28) to produce physiological responses similar to those observed during microgravity exposure.

Another possible cause of orthostatic intolerance is decreased vascular responsiveness to sympathetic output. Several investigators have found that, after real or simulated microgravity in rats, there is decreased vasoconstriction (sensitivity and maximal response) to norepinephrine (and other vasoconstrictors) in portal vein, aorta, and carotid and femoral arteries (10, 32, 34). If this same decrement is also present in the resistance vessels (small arteries, arterioles), this could explain why both rats and humans have impaired vasoconstriction responses after real or simulated microgravity.

The present study determined whether simulated microgravity in rats results in altered microvascular function. Specifically, the in vitro responses to vasoconstrictors, shear stress, and pressure in mesenteric resistance arteries were examined. Mesenteric arteries were chosen because vasoconstriction of this vascular bed is necessary to maintain blood pressure during an orthostatic stress (33). Moreover, it has been reported that after simulated microgravity splanchnic vasoconstriction during exercise in rats is compromised (25) and that there is a decrease in mesentery vascular bed vasosonstriction to infused phenylephrine (31).

We used rat hindlimb suspension to simulate the physiological effects of microgravity. It has been previously shown that this model produces cardiovascular effects similar to those experienced by astronauts. Specifically, both astronauts and hindlimb-suspended rats exhibit loss of blood volume, orthostatic hypotension, and reduced aerobic exercise capacity (3, 24, 25, 40). It was hypothesized that hindlimb suspension would significantly alter small mesenteric artery function.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Animal protocol. The experimental protocol was approved by the University of Iowa Animal Care and Use Committee. Twenty-nine male Sprague-Dawley rats [296.3 ± 8.7 (SE) g body wt] underwent the hindlimb suspension procedure as described by Morey (28) for 28 days. In brief, the tail was bandaged along its length with a hook at the distal end. The hook was attached to a paper clip attached to a swivel and crossbar spanning the top of the cage. This allows the rat full mobility around the cage in a 360° arc. The floor of the cage has a plastic grate that allows the rat the ability to move itself around by grabbing the grate and also allows waste to drop out of the cage. The rats were suspended at an angle of 40-45° as measured from the angle of a line drawn through the anus and shoulder. Twenty-nine control rats (286.6 ± 8.1 g body wt) were housed in the same room in the same type of cage for 28 days. The ambient temperature was maintained at 26 ± 1°C, because it has been previously shown that hindlimb-suspended rats have a drop in body temperature when housed at the standard temperature of 21-23°C (37).

After the 28-day treatment, rats were anesthetized with pentobarbital sodium (Nembutal, 50 mg/kg ip). Hindlimb-suspended rats were injected while suspended and removed from suspension when fully anesthetized. While the animals were anesthetized, a midline incision was made, and the mesentery was tied off with silk sutures and removed. It was placed in a dissecting dish with ice-cold physiological salt solution (PSS; in mM: 119.0 NaCl, 4.7 KCl, 1.2 MgSO4, 1.2 KH2PO4, 25.0 NaHCO3, 2.5 CaCl2, 5.5 glucose, and 0.026 EDTA, pH 7.4).

Isolated-vessel protocol. The mesenteric arteries isolated were a second-order branch off the superior mesenteric artery. These arteries had an internal diameter of 261-388 µm when fully dilated in Ca2+-free PSS + EGTA (1 mM) and pressurized to 70 mmHg. This pressure was used as the baseline pressure during all experiments, because it corresponds with the in vivo pressure in arteries of this size in the rat (5, 12). After isolation, the artery was cannulated at one end with a glass micropipette, fastened with 10-0 nylon opthalamic sutures, and then flushed with PSS to remove any blood. The other end was cannulated, and the vessel was perfused with PSS and pressurized to 70 mmHg by using a pressure servo-control system (Living Systems, Burlington, VT). The vessel was superfused with PSS heated to 37°C and gassed with 95% O2-5% CO2.

Vessel function measurements included responses to vasoconstrictors (norepinephrine, KCl, serotonin), pressure (distensibility, myogenic tone), and shear-stress-induced vasodilation. In most cases, separate vessels were used for the different functional tests.

Responses to vasoconstrictors were determined by first measuring the change in luminal diameter to cumulative doses of norepinephrine (10-9 to 10-4 M), with 2 min between each dose to allow time for the response to stabilize. Vessel viability was confirmed by a reduction in luminal diameter >= 50% of baseline diameter at the highest dose of norepinephrine. Endothelium integrity was then determined by an increase in luminal diameter to acetylcholine (10-5 M) that was >= 80% of baseline diameter. The chamber was then flushed with 400 ml PSS, and the vessel was allowed to equilibrate for a total time of ~30 min. Then responses to increasing doses of KCl (20-100 mM) were measured, the chamber was flushed again, and responses to cumulative doses of serotonin (10-10 to 10-5 M) were measured. Responses to vasoconstrictors were always measured in this order, and endothelium integrity was again confirmed after the highest dose of serotonin by adding acetylcholine (10-5 M).

Active responses to pressure were measured in PSS by increasing the intraluminal pressure in 10-mmHg steps from 10 to 120 mmHg. Each step was maintained for 5 min. Some vessels exhibited spontaneous tone in PSS at pressures >50 mmHg. Because many vessels did not exhibit spontaneous tone, a subthreshold dose (dose that elicits <10% of maximal response) of phenylephrine (10-7 M) was added to the superfusate. Previous investigators have shown that norepinephrine and phenylephrine sensitize arteries to pressure and enhance myogenic tone (38). Responses to pressure steps were measured in the presence of phenylephrine by using the same protocol as with PSS. Passive responses to pressure were measured in Ca2+-free PSS + EGTA (in mM: 121.5 NaCl, 4.7 KCl, 1.2 MgSO4, 1.2 KH2PO4, 25.0 NaHCO3, 5.5 glucose, and 1.0 EGTA, pH 7.4), which fully relaxes the vessel. Myogenic tone was calculated at each pressure as follows: myogenic tone = active diameter/passive diameter · 100.

Responses to shear stress were measured by inducing flow through the vessel. Flow was induced by increasing the height of the inflow PSS perfusion reservoir and decreasing the height of the outflow reservoir an equal distance. This increases inflow pressure and decreases outflow pressure to the same degree but maintains the intraluminal pressure at 70 mmHg, because the cannula resistances were equal. Inflow and outflow pressures were measured with flow-through pressure transducers, and flow was measured with a microflowmeter (model GF-3060, Gilmont Instruments, Barrington, IL). Each flow step was produced by increasing the inflow pressure in increments of 10 mmHg to a maximum of ~130 mmHg and simultaneously decreasing the outflow pressure to a minimum of ~10 mmHg. Flow varied between arteries at each pressure step because of differences in vessel diameter and, therefore, resistance. Maximal flow ranged from 0.570 to 1.437 (SE) µl/s (control: 0.894 ± 0.136; hindlimb suspended: 0.968 ± 0.116 µl/s), which has been shown to produce maximal flow-induced vasodilation in small mesenteric arteries of a similar size under some conditions (6). Shear stress was calculated as follows: shear stress (dyn/cm2) = (4 · viscosity · flow)/(pi · radius3). Diameter responses to shear stress were measured before and after preconstriction with phenylephrine (10-6 M). Vessel diameter responses to flow were expressed relative to the calculated shear stress, because this is the physiological stimulus for vasodilation.

In a second group of experiments, smaller mesenteric artery (third-order branch off the superior mesenteric artery; 157- to 277-µm internal diameter) responses to increasing doses of phenylephrine (10-9 to 10-5 M), acetylcholine (10-9 to 10-5 M), and KCl (20-100 mM) were measured in this order. Vasodilation to acetylcholine (%relaxation) was expressed relative to the preconstricted diameter with phenylephrine (10-5 M), and the passive diameter as determined by addition of Ca2+-free PSS + EGTA (1 mM). Active and passive responses to pressure were also measured as above.

Chemicals. All drugs and chemicals were obtained from Sigma Chemical.

Data analysis and statistics. Norepinephrine, phenylephrine, serotonin, KCl, and acetylcholine dose responses were compared by two-way ANOVA with repeated measures. Drug concentration required to elicit half-maximal vasoconstriction (EC50) was calculated by using a computer program (Kaleidograph, version 3.0.2, Abelbeck Software) with concentration-response data fitted to the equation Y = M1[1 - e(-M2 ×M0)], where Y is the response obtained with a given NE concentration, M1 is the maximal attainable response, M0 is the concentration required for 50% maximum contraction, and M2 is a constant. EC50 was compared between groups by two-tailed unpaired t-test. Vessel dimensions (internal diameter, external diameter, wall thickness, and wall thickness-to-internal diameter ratio) were compared by one-way ANOVA. Diameter responses to shear stress were grouped in 2 dyn/cm2 increments (as graphed) to allow comparison by one-way ANOVA. Passive and active responses to pressure were compared by two-way ANOVA with repeated measures. Myogenic tone was indicated if active diameter was at least 10% smaller than passive diameter. Post hoc tests were performed by using least squares means. Significance in all analyses was determined by P <=  0.05.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

All rats, except one hindlimb-suspended rat that repeatedly escaped the tail harness, successfully completed the protocol. The 28-day hindlimb suspension treatment resulted in significantly less gain in body mass and significantly reduced hindlimb (gastrocnemius, soleus, plantaris) muscle mass compared with the control group (Table 1). Hindlimb muscle atrophy was indicated in the hindlimb suspension group by the decreased hindlimb muscle mass-to-body mass ratio (Table 1). Both absolute and normalized forelimb muscle (extensor carpi radialis) masses were similar between the two groups (Table 1). Adrenal mass was similar between the two groups when normalized to body mass, suggesting that hindlimb-suspended rats were not chronically stressed (7).

                              
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  		Table 1.   Final body, hindlimb muscle (gastrocnemius, soleus, plantaris), and forelimb muscle (extensor carpi radialis) masses

Isolated mesenteric resistance artery (~300-µm internal diameter) function. There were no significant differences in vasoconstriction responses of small mesenteric arteries to the receptor-mediated vasoconstrictors norepinephrine and serotonin or to the depolarization-mediated vasoconstrictor KCl between the two groups (Fig. 1, A-C).


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  		Fig. 1.   Vasoconstriction to cumulative superfused norepinephrine (A), cumulative superfused serotonin (B), and superfused KCl (C) in small mesenteric arteries (~300 µm ID). Values are means ± SE; n, no. of rats. A y-axis of 0 represents baseline diameter; value of 100 would indicate complete occlusion of vessel. Drug concentration required to elicit half-maximal vasoconstriction was not significantly different.

There was no evidence of gross remodeling in arteries of this size as measured by internal diameter, external diameter, or wall thickness-to-internal diameter ratio (Table 2). There were no differences in passive responses to pressure (distensibility; Fig. 2), suggesting that there were no alterations in connective tissue contents.

                              
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  		Table 2.   Small mesenteric artery dimensions when pressurized to 70 mmHg and fully relaxed with Ca2+-free PSS + EGTA (1 mM)



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  		Fig. 2.   Passive changes in diameter in response to pressure in small mesenteric arteries (~300-µm ID). Arteries were fully relaxed in Ca2+-free physiological saline solution + EGTA (1 mM). Diameters were normalized to the diameter at 10 mmHg. Values are means ± SE; n, no. of rats.

Responses of preconstricted arteries (48.2 ± 15.4% of baseline diameter) to increases in shear stress indicated no significant vasodilation responses in either group and no differences between the groups (Fig. 3). There were no significant vasodilation responses in any of the arteries (>10% increase in diameter), regardless of the maximal shear stress reached, except one vessel in the hindlimb-suspended group that dilated 10.6% at a maximal shear stress of 2.1 dyn/cm2. Other maximal diameter responses in this group, however, ranged from dilation of 3.0% to constriction of 14.4%. In the control group, maximal diameter responses ranged from dilation of 4.3% to constriction of 4.6%. Maximal shear stress ranged from 2.1 dyn/cm2 in one hindlimb-suspended artery to 4.7-78.3 dyn/cm2 in the other individual arteries. Mesenteric arteries of a similar size have been shown to vasodilate under some conditions (i.e., pregnancy) to shear stress greater than ~6-7 dyn/cm2 (6). Basal responses of arteries to flow were also tested before preconstriction. The data were not presented, however, because there were no significant vasodilation responses to flow due to the lack of myogenic tone in these vessels.


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  		Fig. 3.   Changes in diameter in response to graded shear stress in small mesenteric arteries (~300-µm ID). Arteries were preconstricted with superfused phenylephrine (10-6 M). Shear stress data group labeled >= 10 dyn/cm2 contains shear stresses ranging from 10.3 to 78.3 dyn/cm2. Values are means ± SE; n, no. of rats.

Active responses to increases in pressure (myogenic tone) were attenuated in the hindlimb-suspended arteries. This was evidenced by a decrease in the frequency of spontaneous myogenic tone exhibited (5 of 11 vessels exhibited significant tone in the control group, 1 of 8 in the hindlimb-suspended group). The magnitude of tone in the single hindlimb-suspended artery that exhibited tone was within 1 SD of the mean response of the control arteries (Fig. 4A). When sensitized with a subthreshold dose of phenylephrine (10-7 M), almost all vessels exhibited myogenic tone (6 of 8 control, 6 of 6 hindlimb suspended). There was, however, a significant decrease in magnitude of tone in the hindlimb-suspended group at all pressures 40 mmHg and greater (Fig. 4B). This difference was not due to a difference in sensitivity to phenylephrine, because there were no significant differences in vasoconstriction responses to a low, medium, and high dose of phenylephrine at a pressure of 70 mmHg between groups [10-7 M: control -11.8 ± 3.4 (SE), hindlimb suspended -6.2 ± 2.7; 10-6 M: control -45.2 ± 3.9, hindlimb suspended -35.2 ± 5.7; 10-5 M: control -74.2 ± 1.2, hindlimb suspended -73.3 ± 1.4% change in diameter], respectively.


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  		Fig. 4.   A: active changes in diameter (myogenic tone) in response to pressure in small mesenteric arteries (~300-µm ID). Only those arteries that exhibited tone (>10% reduction in diameter relative to the passive response) are shown, which include 5 of 11 control arteries and 1 of 8 hindlimb-suspended arteries. B: active changes in diameter (myogenic tone) in presence of superfused phenylephrine (10-7 M) in response to pressure in small mesenteric arteries (~300-µm ID). Diameters were normalized to passive diameters in Ca2+-free physiological saline solution + EGTA (1 mM), where a y-axis value of 100 indicates identical active and passive responses and no myogenic tone. Values are means ± SE; n, no. of rats. * P < 0.05. 

Isolated mesenteric resistance artery (~200-µm internal diameter) function. Smaller mesenteric arteries, which exhibited myogenic tone in one-half of the vessels in both groups without sensitization with a vasoconstrictor, also indicated an attenuation of tone in the hindlimb-suspended group at all pressures 70 mmHg and greater (Fig. 5).


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  		Fig. 5.   Active changes in diameter (myogenic tone) in response to pressure in small mesenteric arteries (~200-µm ID). Diameters were normalized to passive diameters in Ca2+-free physiological saline solution + EGTA (1 mM), where a y-axis value of 100 indicates identical active and passive responses and no myogenic tone. Only those arteries that exhibited tone (>10% reduction in diameter relative to passive response) were evaluated. Values are means ± SE; n, no. of rats. * P < 0.05.

There were no significant differences in responses to phenylephrine (Fig. 6) or KCl (data not shown) between groups. Responses to acetylcholine (Fig. 7) were also not different between groups, indicating that there was no general alteration in agonist-induced endothelium-dependent vasodilation. There were no significant differences in vessel dimensions (Table 2).


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  		Fig. 6.   Vasoconstriction to cumulative superfused phenylephrine in small mesenteric arteries (~200-µm ID). Values are means ± SE; n, no. of rats. A y-axis value of 0 represents baseline diameter; value of 100 would indicate complete occlusion of the vessel. Drug concentration required to elicit half-maximal vasoconstriction was not significantly different.



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  		Fig. 7.   Vasodilation to cumulative superfused acetylcholine in small mesenteric arteries (~200-µm ID) preconstricted with phenylephrine (10-5 M). Values are means ± SE; n, no. of rats. Diameters were normalized to preconstricted diameter (y-axis value of 0), and passive diameter was determined by addition of Ca2+-free physiological saline solution + EGTA (1 mM) (y-axis value of 100). Drug concentration required to elicit half-maximal vasoconstriction was not significantly different.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

We hypothesized that simulated microgravity would result in vascular dysfunction that could contribute to orthostatic intolerance. Our primary finding was that 28-day hindlimb suspension in rats attenuated myogenic tone in small mesenteric arteries and occurred in the absence or presence of vasoconstrictor stimulation. Because myogenic tone contributes to basal peripheral vascular resistance and to increased resistance in response to increased pressure, this attenuated myogenic tone could contribute to the orthostatic intolerance frequently observed in astronauts after spaceflight. The attenuated myogenic tone in the presence of norepinephrine is of particular importance, because norepinephrine release is expected in the mesenteric vascular bed during standing. For example, the difference in average diameter in second-order mesenteric arteries under 70-mmHg pressure in the presence of phenylephrine (control: 235.8, hindlimb suspended: 290.0 µm; Fig. 7) would result in a twofold greater resistance in control vs. hindlimb-suspended arteries. We also found that hindlimb suspension produced 1) no alterations in responses to vasoconstrictors or the vasodilator acetylcholine, 2) no gross remodeling, and 3) no increase in vasodilation to shear stress.

The attenuated myogenic tone in mesenteric arteries is consistent with a recently found reduction in myogenic tone in small skeletal muscle arteries in the rat gastrocnemius after hindlimb suspension (9). Both the mesenteric and gastrocnemius circulations have been shown to have increased blood flow during hindlimb suspension (25, 35). This increased blood flow may be a result of the reduction in myogenic tone, because mean arterial pressure is generally unchanged during hindlimb suspension (3, 11, 24). In contrast, Geary et al. (15) reported increased myogenic tone in small cerebral arteries of rats subjected to hindlimb suspension, which they postulated was in response to increased pressure in the cerebral circulation. The present findings indicate an opposite change in myogenic tone with hindlimb suspension, which could be due to a drop in pressure in the mesenteric vasculature or some other stimulus. Mesenteric and cerebral blood pressures, however, have not been measured in the rat during hindlimb suspension; therefore, these changes are hypothetical. There is evidence, however, that myogenic tone changes in response to chronic changes in pressure. For example, myogenic tone is increased in arteries during development of hypertension in spontaneously hypertensive rats (18).

Geary et al. (15) also found that enhanced myogenic tone in the cerebral circulation after hindlimb suspension was largely due to attenuated release of nitric oxide from the endothelium. This mechanism is possible, but not likely in the mesentery, because the myogenic response in the mesentery is generally not modified by endothelial factors in vitro (36).

In second-order mesenteric arteries, myogenic tone is rarely observed in vitro (36), which is consistent with our results. In third-order and smaller mesenteric arteries, however, Sun et al. (36) consistently observed myogenic tone. We found myogenic tone in only ~50% of third-order arteries, which could be due to the difference in rat strains used in our study vs. the study by Sun et al.

The mechanism of myogenic tone is not completely understood, but it is clear that activation of voltage-gated Ca2+ channels is necessary (2) and that activation of phospholipase C and protein kinase C are involved (17, 21, 30). These aspects of the pathway leading to myogenic tone are similar to the pathway for agonist-induced vasoconstriction, which is the proposed reason for why agonist stimulation enhances myogenic tone (26). Our finding that vasoconstriction responses to KCl-induced depolarization (which activates voltage-dependent Ca2+ channels) are not different between groups indicates that signaling events distal to depolarization are not different between groups. Similarly, responses to agonist-induced vasoconstriction were not different between groups. Agonist stimulation via norepinephrine and serotonin act through G-protein activation and subsequent activation of phospholipase C and protein kinase C. Therefore, our results indicate no differences in signaling events distal to G-protein activation. This lack of difference in the pathway common to agonist stimulation and myogenic tone indicates that the attenuated myogenic response in the hindlimb-suspended arteries is due to differences in some component of the myogenic tone pathway that is not common to the agonist pathway.

Another more recent component of the myogenic response in cerebral and renal arteries is generation of 20-hydroxyeicosatetraenoic acid (16). This molecule is a metabolite of arachidonic acid dependent on a cytochrome P-450 4A enzyme. It is a potent vasoconstrictor released from membrane phospholipids in response to vessel stretch. It acts by inhibiting Ca2+-activated K+ channels, which produces smooth muscle cell depolarization and vessel constriction. It may also contribute to mesenteric artery myogenic tone; therefore, attenuated myogenic tone in hindlimb-suspended arteries could involve this pathway.

Although other investigators have consistently found decreased responsiveness to vasoconstrictors in conduit arteries after hindlimb suspension (10, 32, 34), we observed no change in mesenteric resistance arteries. Thus the responses of conduit arteries do not necessarily represent those of resistance arteries after hindlimb suspension. Moreover, a recent study by Delp (9) indicates that vasconstrictor responsiveness is reduced in rat small arteries from white gastrocnemius muscle, but not the soleus muscle, after hindlimb suspension. Therefore, a generalized reduction in vasconstrictor responsiveness is not indicated in resistance vessels after hindlimb suspension. In resistance arteries, it is not yet clear why there are changes in vasoconstrictor responses to arteries in white gastrocnemius muscle but not in soleus muscle and mesentery. There are no in vivo hemodynamic data in these circulations that could account for these differences.

We found no differences in the gross dimensions of small mesenteric arteries between groups. Because changes in artery dimensions result from changes in flow or pressure, it is probable that there are no changes in flow or pressure of the magnitude necessary to stimulate vascular remodeling. Arterial wall thickness typically increases in response to elevated mean arterial blood pressure (1, 23). With hindlimb suspension at an angle of 40-45°, the bulk of the mesenteric vascular bed is elevated, causing a reduction in hydrostatic pressure. This drop in local pressure is probably insufficient to cause a decrease in arterial wall thickness. With increases or decreases in flow, arteries remodel by increasing and decreasing their diameter (but not wall thickness), respectively (19, 22). We observed no overall changes in internal or external diameter, despite the reported increase (~20%) in basal visceral blood flow during hindlimb suspension (35).

Small mesenteric arteries of the size used in this study typically do not vasodilate significantly to shear stress in vitro, except in some conditions such as pregnancy (6). We made a similar observation in arteries from both control and hindlimb-suspended rats. We tested the possibility, however, that hindlimb suspension might enhance vasodilation to shear stress, because this could contribute to orthostatic intolerance. Although, the results were negative, the high level of preconstriction with phenylephrine (-48.2 ± 15.4% change in luminal diameter) could have masked a mild, but significant, response to shear stress.

In summary, 28-day hindlimb suspension in rats attenuates myogenic tone in small mesenteric arteries. Because of the important contribution this vascular bed makes to total peripheral resistance during orthostatic stress, decreased myogenic tone in this vascular bed could contribute to orthostatic intolerance.


    ACKNOWLEDGEMENTS

We thank Sonia Panigrahy and Bonnie Vogl for assistance with animal care.


    FOOTNOTES

This study was supported by a National Aeronautics and Space Administration (NASA) Graduate Student Researchers Program Fellowship (GSRP97-050) and an American College of Sports Medicine-NASA Space Physiology Research Grant.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Address for reprint requests and other correspondence: C. V. Gisolfi, Dept. of Physiology and Biophysics, Bowen Science Bldg., Univ. of Iowa, Iowa City, IA 52242 (E-mail: carl-gisolfi{at}uiowa.edu).

Received 10 August 1999; accepted in final form 16 November 1999.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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J APPL PHYSIOL 88(4):1199-1206
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