Reduced vascular responsiveness after a single bout of dynamic exercise in the conscious rabbit MARY

GAUKLER

Department

HOWARD

of Physiology,

AND

Northeastern

STEPHEN

E. DICARLO

Ohio Universities

College

of Medicine,

Rootstown,

Ohio 44272

threefold increase in plasma adenosine after 5 min o HOWARD, MARYGAUKLER,ANDSTEPHEN E. DICARLO.R~duced vascular responsiveness after a single bout of dynamic exerstrenuous rowing in human subjects. Supporters of thr cise in the conscious rabbit. J. Appl. Physiol. 73(6): 2662-2667, adenosine hypothesis suggest that it is a mediator of skel

1992.--We measuredagonist-induced changes in iliac artery blood flow velocity (IFV) independent of baroreflex-mediated compensatory mechanismsin chronically instrumented New Zealand White rabbits (n = 8). Animals were instrumented with a Doppler flow probe around the right common iliac artery. A Teflon catheter was inserted into the right iliolumbar artery for local infusion of the vasoactive agonists. Another Teflon catheter was inserted in the left femoral artery for the measurementof pulsatile and meanarterial (MAP) blood pressuresand heart rate (HR). The cu-adrenergicreceptor agonist phenylephrine (PE, 1.32-10.0pg), the &- and &-adrenergic receptor agonist isoproterenol (IP, 0.022-0.11pg), and the purinergic receptor agonist adenosine(AD, 10.0-100.0 pg) were injected into the functionally isolated hindlimb, and dose-responsecurves were generated. Changesin IFV were obtained without changesin MAP or HR. Exercise increasedHR, MAP, and IFV (65.3 & 7.1 beats/min, 11.1t 2.2 mmHg, and 2.2 t 0.3 kHz, respectively). The maximum responsesto PE, AD, and IP were reduced 29.0 t 6.7, 50.7 * 8.5, and 61.0 ,t 8.1%, respectively, after exercise.In conclusion, exerciseattenuated adrenergic and purinergic receptor-mediated vascular responsesin the intact consciousrabbit.

eta1 muscle vasodilation during exercise (10). Recently, in a preliminary investigation, we reporter that a single bout of treadmill running significantly at tenuated a-adrenergic receptor-mediated vascular con traction in an isolated aortic ring preparation (15). Thir in vitro approach provided a direct evaluation of the con tractile properties of aortic vascular smooth muscle inde, pendent of influences from neurohumoral factors. It ir important to note that the effects of a single bout of dy namic exercise on the contractile responsiveness to phen ylephrine in the isolated aortas persisted despite 2 h o: washing in the organ baths. This suggested that the ef, fects of exercise were due not to a constant exposure to : change in environment but rather to a physiological adap, tation to exercise. However, it is unknown whether thiz decreased vascular sensitivity occurs in the intac conscious animal, because it has not been possible to iso, late systemic vascular responses from the baroreflex, mediated compensatory mechanism without the use o: pharmacological intervention (6, 8). It is also unknowr whether a decreased vascular response to agonist-in. adrenergic receptors;blood flow velocity; purinergic receptors; duced vasodilation occurs after a single bout of dynamic vascular smooth muscle exercise. We have developed a model that allows us to directly measure agonist-induced changes in regional blood flow ARTERIOLES are densely innervated by noradrenergic independent of baroreflex-mediated compensatory mechnerve fibers and contain both a- and P-adrenergic recep- anisms in an intact conscious rabbit (Fig. 1). Using this tors. The a-adrenergic receptors, which are directly in- model, we tested the hypothesis that a single bout oj nervated, are most sensitive to norepinephrine released treadmill running attenuates adrenergic and purinergic from sympathetic nerve terminals. The noninnervated receptor-mediated vascular responses. vascular P-adrenergic receptors are most sensitive to circulating epinephrine. However, both receptors can re- METHODS spond to elevated levels of either agonist. Activation of cr-adrenergic receptors results in vasoconstriction, Design. This study was designed to determine whethel whereas P-adrenergic receptors mediate vasodilation. Ara single bout of treadmill running attenuates adrenergic or purinergic receptor-mediated vascular responses in an terioles are therefore capable of both epinephrine-induced vasodilation and norepinephrine-induced vaso- intact conscious rabbit. Experiments were conducted on constriction. Arterioles also dilate in response to adenoeight conscious rabbits (New Zealand White, 1.8 t 0.1 sine; in fact, adenosine is recognized as one of the most kg). Common iliac blood flow velocity (IFV), heart rate potent endogenous vasodilators known. (HR), and pulsatile (AP) and mean arterial blood presLudbrook and Graham (22) examined the hemodysures (MAP) were recorded under control conditions and namic and metabolic responses of rabbits to treadmill during bolus injections of the a-adrenergic receptor agoexercise. Running at a moderate speed of 13 mlmin for I nist phenylephrine (PE, 1.32-10.0 pg), the p1- and &min resulted in a fourfold increase in plasma norepinephadrenergic receptor agonist isoproterenol (IP, 0.022-O. 11 rine and more than a fivefold increase in epinephrine pg), and the purinergic receptor agonist adenosine (AD: concentration. Similarly, Parkinson (25) reported a 10.0-100.0 pg) into the functionally isolated hindlimb 2662

(X61-7567192 $2.00 Copyright 0 1992 the American Physiological Society

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Uoppler

flow probe

infusion

iliolumbar

artery

yJJJytheter

right cummon

iliac

left common

iliac

FIG. 1. Isolated hindlimb model: schematic representation of instrumentation used for experimental protocols. This model allowed us to isolate regional vascular responses from baroreflex-mediated compensatory mechanism in the intact conscious rabbit.

(Fig. 1). These experiments involved determination of vascular responses during three experimental trials: 1) a control condition (controL I), 2) after a single bout of treadmill running (poste~~ise), and 3) a repeated control condition (control 2). Each experimental trial was separated by 248 h of rest. These procedures provided data on the effects of a single bout of treadmill running on adrenergic and purinergic receptor-mediated responses. Instrumentation. The surgical instrumentation (Fig. 1) made it possible to functionally isolate a hindlimb in the intact conscious rabbit. All instrumentation was performed using sterile surgical procedures. Anesthesia was maintained with intramuscular injection of “rabbit cocktail”: zylazine (5 mg/kg), chlorpromazine (2 mg/kg), and ketamine (26 mg/kg); supplemental doses were administered as needed. The rabbits were instrumented with an epoxy cuff-type pulsed Doppler ultrasonic flow probe positioned around the right common iliac artery. Just distal to the flow probe, a Teflon catheter was inserted into the right iliolumbar artery for local infusion of the vasoactive agonists. Additionally, another Teflon catheter was inserted in the left femoral artery for the measurement of AP, MAP, and HR. It is important to note that the experimental model made it possible to change blood flow in the hindlimb without changing systemic MAP, AP, or HR, because we selected dose ranges below those that elicited systemic responses. Thus the hindlimb vasculature was functionally isolated from baroreflex compensation. Catheters were flushed every other day, filled with heparin (1,000 U/ml), and plugged with a paraffinfilled obturator. Animals were monitored for signs of in-

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fection, weighed daily, and treated with antibiotics if necessary. The animals were allowed to recover for lo-14 days before experimentation. At the time of experimentation, all animals had recovered to preoperative weight; they were healthy and gaining weight. Arterial pressure was determined by connecting the femoral arterial catheter to a Gould P23XL pressure transducer that was coupled to a Gould RS3600 recorder. MAP was derived electronically with a low-pass filter. Heart rate was determined with a Gould electrocardiogram (model 20-4615-65, Biotach), which was triggered from the arterial blood pressure pulse. The pulsed Doppler flow probes were connected to a multichannel ultrasonic flow-dimension system with 20-MHz high-velocity modules, constructed by the instrumentation development laboratories at Baylor College of Medicine. The Doppler flow-dimension system measures blood flow velocity in kilohertz Doppler shift, which is directly proportional to absolute blood flow as determined with an electromagnetic system (13, 14). PE, AD, and IP were administered by bolus injection via the catheter placed in the iliolumbar artery. Dose-response curves were obtained for each agonist in two separate control periods and after a single bout of treadmill running. Each dose-response curve consisted of four to six bolus injections. The bolus doses were given at 4-min intervals in ascending order until the entire dose-response curve was obtained. The dose-response curves were always generated in the order of PE, AD, and IP. Normal saline was used as the vehicle for the agents and to flush the catheter. Saline injections did not alter the measured variables, indicating no vehicle or volume effect. Experimental protocol. One week before instrumentation, the rabbits were trained to sit in a standard rabbit holder, which gently restricts them to a sitting position. The head was not restrained. On the day of the experiments, the rabbits were positioned in the same standard rabbit holder, which was positioned inside a Faraday cage that was isolated from all extraneous environmental influences. Rarely did the rabbits exhibit discomfort; if it occurred, the experiments were terminated. On day 1 of the experiment (control I), the animals were adapted to the laboratory environment for 30-45 min before the collection of control data. After the adaptation period, a PE dose-response curve was obtained. The rabbit was then allowed 30 min to recover from the drug administration. Subsequently, an AD dose-response curve was obtained, followed by another 30-min recovery period, Finally, an IP dose-response curve was generated. After data collection, the animals were returned to their housing facilities. On day 2 of the experiment (postexercise) the animals were treated identically to experimental clay I, except in the postexercise trial the adaptation time was replaced by a single bout of treadmill running. Each rabbit ran on a motor-driven treadmill (24 m/min) until exhaustion (17.8 -t 1.9 min). Immediately after exercise (- 10 min), data were collected as described. On day 3 of the experiment (control 2), the rabbits were treated identically to experimental day 1. Data collection took -3.5 h to complete. Each experimental trial was separated by 248 h of rest.

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1. Resting hemodynamic variables during 2 control periods and immediately after exercise TABLE

Control I HR, beatdmin MAP, mmHg IFV, kHz

260.0t9.3 76.0t2.9 4.1t0.3

Postexercise 320.0tll.O* 85.O-t4.8* 6.2t0.6*

0

Control

2

260.0t7.1 71.0+3.0 4.0t0.3

Values are means + SE for 8 rabbits during 3 experimental trials: co&rot 1, 4.2 + 0.6 min postexercise, and control 2. Dynamic exercise significantly increased heart rate (HR), mean arterial blood pressure (MAP), and iliac blood flow velocity (IFV) (65.3 t 7.1 beats/min, P = 0.001; 11.1 t 2.2 mmHg, P = 0.037; and 2.2 t 0.3 kHz, P = 0.005; respectively). There was no significant difference in resting hemodynamic variables between controZ tr&!s 1 and 2. * Significantly different, control vs. postexercise (P 5 0.05).

2. Hemodynamic variables durirtg 3 experimental trials immediately before dose-responsecurves for each agonist were generated

8m 0 Q) > 9 03 =ZE IrJs 0 0 5 0 cv

HR, beats/min PE AD IP

251.3k8.8

256.9t9.2 266.3k10.3

MAP, mmHg PE AD IP IFV, kHz PE AD

76.623.5 76.7t2.4

75.Ok3.1 3.9*0*3 4.2t0.4 4.4t0.4

IP Values

are means

t SE for 8 rabbits

Postexercise

Control

302.5tl3.3* 292.5-1-13.2-t 295.7kl3.1

264.2k10.2 259.2t7.4 284.225.8

75.7t3.4 74.7~4.2 70.3~4.6

75.8t3.3 74.5k3.8 73.723.2

4.6k0.4 4.4t0.5 4.5kO.4

4.OkO.6 4.3t0.4 4.720.5

during

3 experimental

2

-1

-2

-3

-4

control

1

f-

control

2

a -5

I

0

2



I

-

4

I

-

6

I

*

1

810

dose phenylephrine (PSI) FIG. 2. Phenylephrine (PE) dose-response curve. Peak changes (A) in iliac blood flow velocity (IFV) to bolus injections of PE under experimental trials of control 1, postexercise, and control 2. A single bout of treadmill running significantly attenuated a-adrenergic receptor-mediated vascular responses. Values are means t SE (n = 8). * P II 0.05, control vs. postexercise.

7

T

* =E 0 Q) >

A

6

f-control bcontrol

2 1

5

trials.

HR remained significantly elevated immediately before generation of both phenylephrine (PE) and adenosine (AD) dose-response curves. IP, isoproterenol. Significant difference, control vs. postexercise: * P = 0.006;

f-

l.-

TABLE

ControlI

EXERCISE

post-exercise

t P = 0.044.

Calculations and statistical analysis. The dose-response curves were constructed from the peak response to each dose for each individual agonist. Values are means t SE of all individual peak responses recorded at the various dose concentrations. The curves were analyzed using a two-way analysis of variance (ANOVA) with repeated measures. Differences observed were further evaluated by the Bonferroni t test (32). An a level of ~0~05 was used to determine statistical significance (control vs. postexercise). This a level was two sided. RESULTS

Table 1 presents resting HR, MAP, and IFV during the three experimental trials of control 1, postexercise (immediately after exercise, 4.2 t 0.6 min), and control 2. There was no significant (P > 0.05) difference in the resting hemodynamic parameters between controZ 1 and controL 2; therefore these trials were averaged for statistical comparisons with the postexercise trial. A single bout of treadmill running significantly increased HR (65.3 t 7.1 beats/min, P = O.OOl), MAP (11.1 t 2.2 mmHg, P = 0.037), and IFV (2.2 t 0.3 kHz, P = 0.005). Table 2 presents the resting hemodynamic variables immediately before the dose-response curves for each agonist were generated. Table 2 was necessary to demonstrate that MAP and IFV had returned to control levels before generation

o!*T-““” 0 10 20

30

40

50

60

dose adenosine FIG 3. Adenosine (AD) dose-response curve. Peak changes in IFV to bolus injections of AD for control 1, postexercise, and control 2. A single bout of treadmill running significantly attenuated purinergic receptor-mediated vascular responses. Values are means + SE (n = 8).

* P I 0.05, control

vs. postexercise.

of the dose-response curves. However, HR remained significantly elevated immediately before generation of both the PE (P = 0.006) and AD (P = 0.044) dose-response curves. Peak changes in IFV during bolus injections of PE, AD, and IP under the three experimental trials are presented in Figs. 2, 3, and 4, respectively. There were no significant differences in the vascular responses for control I and 2 trials for each agonist; therefore these trials were averaged for statistical comparisons with the vascular response af’ter exercise. A two-way ANOVA indicated that a single bout of treadmill runnine significant;lv de-

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81

j: tpost-exercise jc *

0~

0.02

0.04

0.06

* *

0.08

0.10

dose isoproterenol (Pa FIG. 4. Isoproterenol (IP) dose-response curve. Peak changes in IFV to bolus injections of IP for control I, p&exercise, and control 2. A single bout of treadmill running significantly attenuated P-adrenergic receptor-mediated vascular responses. Values are means t SE (n = 8). * P 5 0.05, control vs. postexercise.

creased the vascular response to each agent. The repeated-measures ANOVA demonstrated a significant treatment effect (control vs. postexercise) for PE (P = 0.034), AD (P = 0.013), and IP (P = 0.003). This treatment effect indicates that the same doses of each agonist produced a significantly smaller effect on IFV postexercise. There were no significant treatment X dose interactions for PE (P = 0.185), AD (P = 0.587), or IP (P = 0.138). Although the ANOVA indicated a difference in IFV response postexercise, a Bon .ferroni t test was conducted to determine exactly which . doses were attenuated postexercise. This test showed that a single bout of treadmill running significantly (P < 0.05) attenuated the vascular response to each agonist at every dose. DISCUSSION

The major finding in this study is that a single bout of treadmill -running significantly attenuated adrenergic and purinergic receptor-mediated vascular responsiveness in the intact conscious rabbit. These results are confirmed by the repeated-measures ANOVA, which revealed two important outcomes. First, there was a significant treatment effect (control vs. postexercise) for all three agonists. That is, the same doses of each agonist produced significantly smaller effects on IFV postexercise. These results sugges lt that a sing1 .e bout of dynamic exercise possibly reduced the n .umber 0 f adrenergic and purinergic receptors or attenuated th .e receptor transduction process (functional reduction of receptors). In addition, there were no significant treatment X dose interaction .sfor a.ny of the agonists. T his outcom .e i.ndicates that the control and postexercise curves were parallel (i.e., had similar shapes) and may further suggest that exercise had no effect on receptor affinity. For the first time, it was possible to change blood flow in the hindlimb of an intact conscious rabbit without changing arterial blood pressure or heart rate. This is an important consid-

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2665

eration because any change in hemodynamic variables would alter baroreflex function, which in turn would indirectly affect vascular responsiveness and blood flow velocity. Therefore it is important to reiterate that mean arterial blood pressure, pulse pressure, and heart rate were never altered by any of the bolus injections. Thus we are confident that baroreflex-mediated compensatory mechanisms were not elicited and that we directly evaluated the effects of a single bout of exercise on vascular function. The ability of the vasculature to respond to a-adrenergic receptor activation was decreased by a single bout of treadmill running (Fig. 2). Thus one may postulate that the ability of the vasculature to constrict in response to sympathetic nervous system activation may be significantly attenuated. Indirect support for this concept is provided by Bjurstedt et al. (l), who examined the responses of individuals to 70’ head-up tilt before and after strenuous exercise. These investigators reported an increased incidence of orthostatic collapse immediately after a single bout of strenuous leg exercise. Although several mechanisms may be responsible, Bjurstedt et al. concluded that the orthostatic collapse was due to a decline in systemic resistance, inasmuch as cardiac filling pressures were not significantly different in the postexercise period. The mechanism responsible for the decline in systemic resistance may be a reduced response to aadrenergic receptor activation. Several additional studies have reported orthostatic intolerance in individuals after a single bout of exercise; however, the mechanisms responsible were unknown (7,29). Although reduced cardiac filling was assumed to be responsible for postexercise orthostatic intolerance (1), it now appears likely that the inability to tolerate orthostatic stress after exercise may be due to a reduced ability of the vasculature to respond to a-adrenergic receptor activation. Although not investigated in this study, the reduced vasoconstrictor response to a-adrenergic receptor activation may contribute to the incidence of postexertional hypotension, a postexercise depression in systemic arterial blood pressure after a single bout of dynamic exercise (1, 5, 7, 9, 12, 24, 29, 30, 34). This response has been documented in normotensive and hypertensive animals (24, 30, 34). Floras et al. (9) monitored postganglionic sympathetic nerve activity (SNA) directly from the peroneal nerve in individuals with borderline hypertension before and after a single bout of treadmill running. The authors concluded that a single bout of dynamic exercise sufficient to produce postexertional hypotension lowers postganglionic muscle SNA. Furthermore, they postulated that a decrease in SNA may be a component of the mechanism responsible for postexertional hypotension. Hagberg et al. (12) found a significant decrease in systolic blood pressure, cardiac output, and stroke volume, but no change in heart rate and an increase in total peripheral resistance after a single exercise bout. These results suggest that a reduced cardiac output is responsible for the hypotensive effects of exercise. Similarly, Overton et al. (24) recorded regional vascular resistances before and immediately after a single bout of dynamic exercise (treadmill running) in spontaneously hypertensive rats. Although arterial blood pressure was reduced, there

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was no change in regional vascular resistance postexercise. Because heart rate was reduced, the investigators concluded that the exercise-induced hypotension was due to a decreased cardiac output. However, recent results from the same laboratory failed to record an exercise-induced reduction in cardiac output after a single bout of dynamic exercise (5). In the present study, a difference was also observed in the vascular response to IP. The dose-response curve (Fig. 4) illustrates an attenuated response of the vasculature to P-adrenergic receptor-mediated vasodilation after exercise. This finding is supported by two studies that examined ,&adrenergic receptor alterations after a single bout of dynamic exercise (2, 11). Friedman et al. (11) reported a decrease in cardiac ,@adrenergic receptor responsiveness after 1 h of treadmill running at 60-70% maximum heart rate in adult mongrel dogs. Similarly, Butler et al. (2) reported a decrease in P-adrenergic receptor sensitivity in human lymphocytes after 15 min of treadmill running at 90% maximal heart rate. These data support our findings of an attenuated ,&adrenergic receptor response after a single bout of treadmill running. The response to AD, a major metabolic vasodilator present in high concentrations during and after exercise, was also significantly attenuated after treadmill running. The attenuated vascular response to AD and IP suggests an exercise-induced attenuation of membrane receptors and/or postreceptor intracellular vasodilator mechanisms. However, because AD and IP both stimulate the adenylyl cyclase-adenosine 3’,5’-cyclic monophosphate (CAMP) pathway through G protein-regulated mechanisms (18), it is nut possible to determine whether the exercise bout altered receptor or intracellular secondmessenger mechanisms. We did not investigate the mechanisms responsible for the attenuated response to AD; however, it is nut likely that components within the CAMP second-messenger system are responsible for our observations. If the decrease in vascular responsiveness were due to an alteration in the second-messenger system, one might expect that the response to PE would be enhanced, because the vasoconstrictor response would not be opposed by the dilator system. Interestingly, these findings of an attenuated response to AD after a single bout of exercise are in contrast to studies (6,19,20) that have examined the coronary vascular response to AD in exercise-trained animals. The mechanisms responsible for the attenuated adrenergic and purinergic receptor-mediated vascular responses are unknown; however, factors that are known to alter vascular receptor responsiveness (high concentrations of active hormones, increased body temperature, local acidosis, and increasing levels of Pco,) are significantly increased during and after a single bout of dynamic exercise (3,4,16,17,23,26--28,31). For example, it is well known that changes in the concentrations of many biologically active substances can regulate target organ sensitivity to the same substance (l&21). That is, exposure of target cells to high concentrations of a hormone results in subsequent decreases in sensitivity, an effect termed desensitization, refractoriness, tolerance, or tachyphylaxis (21). During exercise, catecholamines are significantly increased (16, 17), which may result in a

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functional downregulation of a- and/or P-receptors (3,4, 11, 21, 33). In addition, during exercise, plasma adenosine is significantly increased (25). Accordingly, one would postulate that the vascular response to adenosine would be attenuated. Roberts et al. (26) reported that the affinity of aadrenergic receptors for norepinephrine was attenuated as incubation temperature increased above 23*C. Additionally, Stokke et al. (31) reported that acidosis caused by an increase in the PCO, shifted the norepinephrine dose-response curve to the right. Because a single bout of dynamic exercise significantly increases body temperature (27, 28) and decreases local pH (16, 17), one could postulate that a single bout of treadmill running might decrease vascular sensitivity. In conclusion, factors associated with a single bout of treadmill running attenuated adrenergic and purinergic receptor-mediated vascular responses in the intact conscious rabbit. Although we did not directly investigate these factors in this study, we postulate that they may include 1) increased catecholamines, 2) increased body temperature, and 3) increased lactic acid production. This work has been supported by National Heart, Lung, and Blood Institute Grant HL-45245. Address for reprint requests: S. E. DiCarlo, Dept. of Physiology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272. Received 12 November 1991; accepted in final form 19 June 1992. REFERENCES H., G. ROSENHAMER, U. BALLDIN, AND V. KATKOV. Orthostatic reactions during recovery from exhaustive exercise of short duration. Acta Physiol. Scund. 119: 25-31, 1983. 2. BUTLER, J., J. G. KELLY, K. O’MALLEY, AND F. PIDGEON. P-Adrenoceptor adaptation to acute exercise. J. physiol. Lo&. 344: ll31. BJURSTEDT,

117,198X 3. COLUC~I,

W. S., AND R. W. ALEXANDER. Norepinephrine-induced alteration in the coupling of a,-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells. Proc. N&L.

Aad. Sci. USA 83: 1743-1746,1986. 4. COLUCCI, W. S., M. A. GIMBRONE,

5.

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AND R. W. ALEXANDER. Phorbol diester modulates a-adrenergic receptor-coupled calcium efflux and a-adrenergic receptor number in cultured vascular smooth muscle cells. Circ. Res. 58: 393-398, 1986. DEVINE, M. D., L. A. SEBASTIAN, K. A. MONNIN, AND C. M. TIPTON. Training and post-exercise hypotension with hypertensive rats (SHR) (Abstract). Physiologist 34: 267, 1991. DICARLO, S. E., R. W. BLAIR, V. S. BISHOP, AND H. L. STONE. Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation. J. Appl. Physiul. 66: 421-428, 1989. EICHNA, L. W., S. M. HORVATH, AND W. B. BEAN. Post-exertional orthostatic hypotension. Am. J. Med. Sci. 213: 641-654, 1947. EVANS, J. M., J. N. FUNK, J. B. CHARLES, D. C. RANDALL, AND C. F. KNAPP. Endurance training in dogs increases vascular responsiveness to an ar,-agonist. J. Appl. Physiol. 65: 625-632, 198%. FLORAS, J. S., C. A. SINKEY, P. E. AYLWARD, D. R. SEALS, P. N. THOREN, AND A. L. MARK. Postexercise hypotension and sympathoinhibition in borderline hypertensive men, Hypertension Dal-

las 14: 28-35,19%9. 10. FORRESTER, T. Adenosine or adenosine triphosphate? In: VusodiZution, edited by P. M. Vanhoutte and I. Leusen. New York: Raven, 1981, p. 205-229. D. B., G. A. ORDWAY, AND R. S. WILLIAMS. Exercise11. FRIEDMAN,

induced functional desensitization of canine cardiac P-adrenergic receptors. .J. Appl. PhysioZ. 62: 1721-1723, 1987. 12. HAGBERG, J. M., S. J. MONTAIN, AND W. H. MARTIN. Blood pres-

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13. 14.

15. 16. 17. 18.

19. 20. 21.

22. 23.

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sure and hemodynamic responses after exercise in older hypertensives. J. Appl. Fhysiol. 63: 270-276, 1987. HARTLEY, C. J., AND J. S. COLE. An ultrasonic pulsed Doppler system for measuring blood flow in small vessels. J. Appl. Physiol. 37: 626-629,1974. HAYWOOD, J. R., R. A. SHAFFER, C. FASTENOW, G. D. FINK, AND M. J. BRODY. Regional bIood flow measurement with pulsed Doppler flowmeter in conscious rat. Am. J. Physiol. 241 (Heart Circ. Physiol. 10): H273-H278, 1981. HOWARD, M. G., S. E. DICARLO, J. N. STALL~NE. Acute exercise attenuates phenylephrine induced contraction of rabbit isolated aortic rings. IMed. Sk. Sports Exercise 24: 1102-1107, 1992. JOVER, B., B. P. MCGRATH, AND J. LUDBROOK. Haemodynamic and metabolic responses of laboratory rabbits to near-maximal treadmill exercise. C&z. Exp. Purmacol. Physiol. 14: 811-823, 1987. KLUGER, M. J., E. R. NADEL, M. HITCHCOCK, AND J. A. J. STOLWIJK. Energy balance and lactic acid production in the exercising rabbit. Am. J. Physiol. 223: 1451-1454, 1972. KUKOVETZ, W. R., G. POCH, AND S. HOLZMAN. Cyclic nucleotides and relaxation of vascular smooth muscle. In: Vusodilution, edited by P. M. Vanhoutte and I. Leusen. New York: Raven, 1981, p. 339-353. LAUGHLIN, M. H. Effects of exercise training on coronary transport capacity. J. Appl. Physiot. 58: 468-476, 1985. LAUGHLIN, M. H., K. A. OVERHOLSER, AND M. J. BHATTE. Exercise training increases coronary transport reserve in miniature swine. J, Appl. Physiol. 67: 1140-1149, 1989. LEFKUWITZ, R. J., M. G. CARON, AND G. L. STILES. Mechanisms of membrane-receptor regulation. Biochemical, physiological, and clinical insights derived from studies of adrenergic receptors. N. EngZ. J. Med. 310: 1570~X179,19&4. LIJDBROOK, J., MD W. F. GRAHAM. Circulatory responses to onset of exercise: role of arterial and cardiac baroreflexes. Am. J. Physiol. 248 (Heart Circ. Physiot. 17): H457-H467, 1985. LURIE, K. G., G. TSUJIMOTO, AND B. B. HOFFMAN. Desensitization of alpha-l adrenergic receptor-mediated vascular smooth muscle contraction. J. Pharmucol. Exp. Ther. 234: 147-152, 1985.

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Reduced vascular responsiveness after a single bout of dynamic exercise in the conscious rabbit.

We measured agonist-induced changes in the iliac artery blood flow velocity (IFV) independent of baroreflex-mediated compensatory mechanisms in chroni...
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