INTRODUCTION

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ARTERIAL PRESSURE (AP) is reduced below preexercise levels after a single bout of low-intensity, short-duration, dynamic exercise (10, 20). The postexercise hypotension (PEH) has been demonstrated in hypertensive individuals (1, 11, 12) and animals (4, 5, 9, 21). In hypertensive individuals, PEH is most often associated with elevations in cardiac output (CO) as well as reductions in peripheral resistance (15) and sympathetic nerve activity (SNA) (11, 15). It is important to note, however, that the hemodynamic factors mediating PEH have not been determined in hypertensive animals.

For results obtained in animal models of PEH to have clinical significance, the hemodynamic responses in hypertensive animals must be similar to the responses in hypertensive individuals. Furthermore, the overall hemodynamic responses and how they are mediated must be similar. These are important considerations because if postexercise hemodynamic responses are similar in hypertensive individuals and animals, then the animal model provides a situation where invasive manipulation of the autonomic nervous system can be performed to acquire new information, to test hypotheses, and to develop interventions designed to prevent the morbidity and mortality associated with hypertension.

The purpose of this study was to test the hypothesis that postexercise reductions in AP are associated with reductions in total peripheral resistance (TPR) and SNA. This purpose was achieved by measuring AP, heart rate (HR), and CO before, during, and after a single bout of dynamic exercise in spontaneously hypertensive rats (SHR). In a second group of SHR, AP and HR were also measured before, during, and after exercise, whereas lumbar SNA (LSNA) was measured before and after exercise.

	METHODS

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Design

Surgical Procedures

Protocol 1. All instrumentation was performed using aseptic procedures. Rats were anesthetized with an intramuscular injection of xylazine (8 mg/kg), chlorpromazine hydrochloride (4 mg/kg), and ketamine hydrochloride (40 mg/kg). Supplemental doses were administered as needed. A right thoracotomy was performed through the third intercostal space. The sleeve of the pericardium that extends onto the ascending aorta was dissected free of surrounding tissue. A 3.0-mm epoxy-type Doppler ultrasonic flow probe was positioned around the vessel. The flow probe wires were tunneled subcutaneously and exteriorized at the back of the neck. The animals were allowed at least 7 days to recover from the surgery. During the recovery period, animals were carefully monitored for signs of infection and weight loss, familiarized with running on a motor-driven treadmill, and trained to rest quietly in a large Plexiglas box. At the end of the recovery period, all animals were healthy and gaining weight. At this time, the rats were anesthetized as described above, and a Teflon catheter was inserted into the descending aorta via the left common carotid artery for measurements of AP and HR. The catheter was tunneled beneath the skin and exteriorized at the back of the neck. The arterial catheter was flushed daily with heparinized saline, filled with heparin (1,000 U/ml), and plugged with a paraffin-filled obturator. The animals were allowed at least 4 days to recover from the surgery. During the recovery period, animals were again monitored for signs of infection and weight loss.

Protocol 2. Rats were anesthetized with pentobarbital sodium (45 mg/kg ip), and a Teflon catheter was placed into the descending aorta as described for protocol 1. Subsequently, the lumbar sympathetic trunk was approached between L₃ and L₅ by a ventral abdominal approach. The aorta was reflected ventrally, and the left psoas muscle was reflected laterally to expose the sympathetic trunk. The sympathetic trunk lies on the quadratus lumborum muscle located under the aorta. To avoid touching the nerve, we removed a small portion (5-10 mm) of the surrounding muscle, creating a pocket around the nerve. After the pocket was filled with warm saline, bipolar electrodes were placed around the isolated lumbar sympathetic trunk for the recording of LSNA. The nerve was not touched by the surgical instruments, and therefore it maintained its connective tissue and blood supply. Each electrode was constructed of a multistranded stainless steel Teflon-coated wire (part no. 316 SS 7/44T, Medwire, Mount Vernon, NY) with the exposed end wound into a single loop. Silicone gel (Wacker Sil-Gel 604) was used to isolate the electrodes from the surrounding tissue and to ensure contact with the nerve. A surgical steel suture was used to close the abdominal muscle and to serve as the ground electrode. The recording electrodes and ground electrode were tunneled beneath the skin and exteriorized at the back of the neck. The experiments were performed either 1 or 2 days after surgery.

Experimental Measurements

SNA signals were initially amplified (1,000-5,000×) with a Grass P511 differential preamplifier and high-impedance probe (HIP 511GA, West Warwick, RI). The probe, amplifier, and animal were located inside a shielded Faraday cage. The low- and high-pass filters were set at 30-, 100-, and 1,000 Hz. The action potentials were displayed on an oscilloscope (Tektronix 5111A, Beaverton, OR) and monitored with a Grass AM8 audio monitor. Whole nerve activity was obtained by rectifying and integrating the action potentials with a root mean square (RMS) integrator, which was coupled to a Gould RS3600 (Cleveland, OH) recorder. Mean nerve activity was derived electronically using a low-pass filter with a time constant of 3.2 s. All data were displayed on a physiograph (model RS3600, Gould Instruments) and were sampled by a data-acquisition system and laboratory computer (MacLab 8 analog-to-digital converter and Macintosh computer, Milford, MA) for subsequent analysis. Background noise for LSNA was determined on the day of the experiment at the end of the postexercise period, after the animal was killed. Postmortem noise was subtracted from the raw LSNA recording before analysis. Extreme care was taken to distinguish LSNA from an electromyogram or movement artifact. Artifacts were identified as a distinctive change in the audible signal or changes in the average burst height and/or shape. Only data sections free of artifacts were analyzed.

Experimental Procedures

Evaluation of LSNA

Data Analysis

	RESULTS

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Effect of Exercise on MAP and HR

View larger version (38K): [in this window] [in a new window]   Fig. 1.   Ten-second recordings of lumbar sympathetic nerve activity (LSNA), arterial pressure (AP), and heart rate (HR) in preexercise (A) and postexercise conditions (B). After a single bout of dynamic exercise, LSNA and AP were reduced below preexercise values. RMS, root mean square; bpm, beats/min.

View larger version (27K): [in this window] [in a new window]   Fig. 2.   Mean arterial pressure (MAP) (A) and HR (B) before, during, and after a single bout of dynamic exercise. A single bout of dynamic exercise resulted in a postexercise reduction in MAP of 15 ± 4 mmHg (10 min after exercise). This hypotension persisted throughout the postexercise period. Despite the significant reduction in MAP after exercise (*P < 0.05, pre- vs. postexercise), preexercise and postexercise HR values did not differ significantly (P > 0.05, pre- vs. postexercise). Dashed lines, average preexercise values.

HR before, during, and after exercise was determined during two experimental protocols. HR responses for protocol 1 and protocol 2 did not differ significantly (P > 0.05); therefore, HR responses were averaged and are presented in Fig. 2B. HR was 347 ± 14 beats/min before exercise (0 min) and increased to 497 ± 7 beats/min during exercise (10 min, P < 0.05). At 40 min of exercise, HR was 494 ± 5 beats/min. Ten minutes after exercise, HR decreased to 386 ± 11 beats/min. The steady-state HR after exercise was not significantly different from the preexercise HR.

Effect of Exercise on CO and TPR (Protocol 1)

View larger version (28K): [in this window] [in a new window]   Fig. 3.   Cardiac output (CO) (A) and total peripheral resistance (TPR) (B) before, during, and after a single bout of dynamic exercise. A single bout of dynamic exercise resulted in a postexercise reduction in TPR of 8.8 ± 2 mmHg/kHz (10 min after exercise). This reduction in TPR persisted throughout postexercise period. In contrast, CO was elevated 1.5 ± 0.4 kHz (10 min after exercise) and remained elevated throughout the postexercise period (*P < 0.05, pre- vs. postexercise). Dashed lines, average preexercise values.

TPR decreased from 28 ± 3 mmHg/kHz before exercise (0 min) to 22 ± 2 mmHg/kHz during exercise (10 min, P < 0.05). At 40 min of exercise, TPR was 18 ± 1 mmHg/kHz. TPR remained decreased (19 ± 2 mmHg/kHz) after exercise (10 min, P < 0.05). Thus TPR was decreased by 8.8 ± 2 mmHg/kHz 10 min after exercise and remained significantly lower than preexercise values for the entire postexercise period.

Preexercise and Postexercise LSNA (Protocol 2)

View larger version (16K): [in this window] [in a new window]   Fig. 4.   LSNA before and after a single bout of dynamic exercise. A single bout of dynamic exercise resulted in a postexercise reduction of LSNA by 48 ± 5% (10 min after exercise). This reduction in LSNA persisted throughout the postexercise period (*P < 0.05, pre- vs. postexercise). Dashed line, average preexercise value.

	DISCUSSION

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Results from this study demonstrate that after a single bout of dynamic exercise, AP, SNA, and TPR are reduced while CO is elevated above preexercise levels. These results suggest that the postexercise reductions in AP are due, in part, to reductions in TPR. Furthermore, the reductions in TPR are due, in part, to reductions in SNA. The PEH was not due to reductions in CO because CO remained elevated in the postexercise period. The design of this study did not include a postexercise recording period that was long enough to demonstrate that both SNA and blood pressure had returned to preexercise levels. A design that included monitoring these parameters until they had returned to preexercise baseline levels would have strengthened the results of this investigation.

The reduction in SNA in SHR after a single bout of dynamic exercise is supported in work by Thorén and colleagues (26, 29). These investigators reported that renal (26) and mesenteric (29) SNA were reduced after prolonged stimulation of the sciatic nerve in SHR. The reduction in SNA may be due to a resetting of the operating point of the arterial baroreflex to a lower pressure (4, 7, 13, 14). It has also been proposed that postexercise sympathoinhibition may be mediated by a facilitation of inhibitory cardiopulmonary reflexes because cardiac afferent blockade attenuated the hypotensive effect of a single bout of dynamic exercise (9), and other investigators (1, 6) have shown that the inhibitory influence of cardiac afferents on the circulation may be enhanced after exercise. The reduction in SNA may be beneficial for individuals with hypertension. For example, an increase in sympathetic activity and/or responsiveness is associated with the development and maintenance of hypertension (3, 19, 27). Furthermore, reductions in sympathetic activity may be important in the prevention of cardiac arrhythmias. It has been shown both experimentally and clinically that increases in sympathetic activity are involved in the development of ventricular fibrillation, a major cause of cardiac sudden death (2, 23-25). Therefore, any intervention that decreases SNA, such as mild-to-moderate dynamic exercise, may contribute to a reduction in AP and help to prevent cardiac arrhythmias. Our findings of a postexercise reduction in SNA support the findings of a number of studies in hypertensive individuals (6, 11).

The postexercise reduction in TPR may be due to the reduction in SNA and a decreased vascular responsiveness to -adrenergic receptor activation. Recent evidence has shown that a single bout of dynamic exercise significantly attenuated the vasoconstrictor response to phenylephrine in an isolated aortic ring preparation (17) and in the intact conscious rabbit (18) and rat (22, 28). This suggests that the ability of the vasculature to respond to a change in SNA or a sustained catecholamine increase after exercise is significantly reduced. Because the vasculature is less responsive to an elevated plasma catecholamine concentration after exercise, a higher level of SNA may be required to maintain AP. However, a single bout of dynamic exercise sufficient to produce postexertional hypotension has been observed to lower postganglionic muscle SNA and plasma norepinephrine concentration (6, 10, 13). These effects could explain the significant postexercise reduction in TPR (6, 8). The reduction in TPR may be beneficial for individuals with hypertension in terms of lowering resting AP and improving overall cardiovascular function. Our findings of a postexercise reduction in TPR support the findings of studies in hypertensive individuals (6, 15).

The postexercise elevation in CO (Fig. 3A) is due to an increase in stroke volume inasmuch as preexercise and postexercise HR values were not different (Fig. 2B). An increased preload and/or myocardial contractility and decreased afterload may contribute to the increase in stroke volume. The elevation in CO may be beneficial for improving overall cardiovascular function. For example, it is generally accepted that there is an excess postexercise oxygen consumption. Therefore, an elevated CO may be required to facilitate this enhanced oxygen consumption. In addition, a postexercise elevation in CO would be beneficial in maintaining tissue perfusion and allowing adequate recovery from the metabolic demands of the exercise. Our findings of a postexercise elevation in CO are consistent with results from hypertensive individuals (6, 15).

In summary, results from this study demonstrate that a single bout of dynamic exercise reduces AP. The new finding is that the decrease in AP was associated with a decrease in SNA and TPR and an increase in CO in the SHR. Our results from hypertensive rats are consistent with previous results obtained from hypertensive individuals. Taken together, these data suggest that the SHR may be a useful and applicable model for understanding PEH in hypertensive individuals.