In a previous study prolonged low-frequency muscle stimulation in the hind leg of the spontaneously hypertensive rat (SHR) was shown to induce a reduction in blood pressure (about 15 mmHg) that lasted for many hours. We showed in that study that endorphin and serotonin systems were involved. In the present study drugs with selective affinity for the serotonin (5-HT) receptors were used to analyse further the involvement of different serotonin systems. In one group of SHR, a prestimulatory dose of metitepine maleate (a 5-HT1 and 5-HT2 receptor antagonist) completely abolished the post-stimulatory depressor response. The long-lasting depressor response was still present, although less pronounced, after a bolus dose of the 5-HT2 blocking agent ritanserin (R 55667) at the start of stimulation. The 5-HT3 receptor antagonist ICS 205-930 did not influence the response at all, nor did the selective 5-HT1a receptor agonist 8-OH-DPAT enhance the depressor response. These results indicate that the reduction in blood pressure after muscle stimulation is mainly mediated by the 5-HT1 receptor.

In a previous study, prolonged low‐frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long‐lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5‐HT) systems were involved. More recently, we have shown that the 5‐HT1 receptors are involved in the post‐stimulatory decrease in blood pressure.In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 ±10% (P < 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h.One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post‐stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5‐HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5‐HT1&2 receptor antagonist) abolished the post‐stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205–930 (5‐HT2 and 5‐HT3 blocking agents respectively).In another group of experiments, the serotonin receptor antagonists were administered post‐stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.Thus, intact 5‐HT systems were necessary to elicit the analgesia to muscle stimulation and the response was mediated by the 5‐HT1 receptor. However, the results indicate that serotonin is not required to maintain the analgesia once it has been elicited.

We have previously shown that prolonged low-frequency muscle stimulation, inducing contractions of the gastrocnemius muscle, in conscious spontaneously hypertensive rats leads to an opioid-mediated post-stimulatory reduction in blood pressure and analgesia. In the present study we investigated whether muscle stimulation would also induce a post-stimulatory reduction in behavioural activity in the spontaneously hypertensive rats. Selective opioid receptor antagonists were used to analyse the involvement of endogenous opioids. Muscle stimulation, lasting 60 min, induced a post-stimulatory sedation that outlasted the stimulation for hours. Sniffing, locomotor activity and total behavioural activity were significantly reduced. The post-stimulatory reduction in activity was reversed back to control levels by a high dose of naloxone (15 mg kg-1 i.v.). The selective mu-receptor antagonist beta-funaltrexamine, given intracerebroventricularly before stimulation, did not influence the development of the post-stimulatory drop in activity. The delta-receptor antagonist ICI 154,129 had no effect at all on the already developed sedation, whereas MR 2266 BS, a kappa-receptor antagonist (3 mg kg-1 i.v.), completely reversed the drop in activity. These results show that muscle stimulation gives rise to an opioid-mediated post-stimulatory reduction in activity in spontaneously hypertensive rats. The results also indicate the involvement of the opioid kappa-receptor in the behavioural response.

In a previous study, electrically induced contractions of the gastrocnemius muscle in conscious spontaneously hypertensive rats were shown to induce a blood pressure reduction of 15-20 mmHg lasting several hours. We showed in that study that endogenous opioid systems were involved. In this study, drugs with selective affinity for different opioid receptors were used to analyse further the involvement of endogenous opioid systems in the post-stimulatory drop in blood pressure in spontaneously hypertensive rats. Prestimulatory intracerebroventricular administration of beta-FNA (a mu-receptor antagonist) did not significantly influence the response at all, nor did a lower intravenous dose of naloxone reverse the post-stimulatory drop in blood pressure. High-dose naloxone (15 mg kg-1) increased post-stimulatory blood pressure by around 10 mmHg. About 50% of the drop thus remained after this treatment. A similar, partial reversal of the decreased blood pressure was seen after intravenous administration of a delta-receptor antagonist, ICI 154,129. However, the depressor response was completely reversed by a low intravenous dose of MR 2266 BS (a kappa-receptor antagonist). These results suggest that the reduction in blood pressure after muscle stimulation is mainly mediated by the opioid kappa-receptor. A certain involvement of the delta-receptor is also indicated.

In a previous study, prolonged low-frequency muscle stimulation, inducing dynamic contractions in the hind leg of unanaesthetized rats, was shown to give rise to a hypoalgesia. The increase in pain threshold, measured as squeak threshold to noxious electric pulses, lasted 3 h. In the present study, the involvement of the endogenous opioid system in the post-stimulatory analgesia was investigated using selective opioid receptor antagonists. The post-stimulatory analgesia was completely reversed back to prestimulatory control levels by naloxone, 1 mg kg -1 . ICI 154, 129 and MR 2266 BS, selective δ- and ±-receptor antagonists respectively, did not significantly influence the post-stimulatory analgesia, although ICI 154, 129 had a minor pain threshold-lowering effect. Rats pretreated with β-funaltrexamine, a μ-preceptor antagonist, did not exhibit any post-stimulatory analgesia. These results suggest that opioid systems are involved in the increase in pain threshold after muscle stimulation and that the analgesic response is both elicited and maintained by the μ-preceptor.

The effect of chronic voluntary exercise on resting blood pressure and heart rate was measured in two different age groups of spontaneously hypertensive rats (SHR). In the younger group, left ventricular dimensions were also measured. The younger group was 9 weeks old at the start of the experiment and was in a period of rapid blood-pressure rise. The older group, 13 weeks old at the start of the experiment, already had established hypertension. During a period of 6 weeks, the animals ran spontaneously in wheels mounted in their cages and reached a maximum of 6-7 km per 24 h. Age-matched, sedentary SHR were used as controls. Both groups of runners showed a decrease in body weight in comparison to controls. The younger runners exhibited a delayed onset of hypertension. They also showed a significantly increased left ventricular (LV) end-diastolic volume for every measured end-diastolic pressure between 7.5 mmHg and 20 mmHg (P less than 0.05). This suggests the development of a structural growth-dependent increase of the internal LV radius while LV weight and wall-to-lumen ratio were largely unaltered in younger runners compared with controls. In SHR with established hypertension, physical training did not reduce arterial blood pressure but heart rate was significantly lower than in the controls. These results thus indicate that an early onset of physical exercise in SHR may delay the development of hypertension. In addition, a more favourable cardiac design could also be seen.

In the present study we investigated the influence of voluntary exercise on exploratory behavior and on aggression in the spontaneously hypertensive rat (SHR). Twenty-four SHR (8 weeks old) were randomly assigned to either an exercise group or a sedentary control group. The animals in the exercise group exhibited a spontaneous wheel running activity of 5-6 km/day during 6 weeks. The characteristic hyperexploratory behavior of SHR was lowered in the exercise group (p less than .001) as compared to the control group. The runners also showed a tendency for less aggression. In the postexercise period, when the runners' wheels were locked, the exercise group had a significant rise in aggression (p less than .01) vs the controls. The exploratory behavior returned immediately to the level of the controls, but we found no further increase in any of the parameters measured. However, the runners showed a type of displaced aggression exhibited as digging and biting in the test cage. This evidence suggests that voluntary exercise lowers the hyperexploratory behavior and aggression in the SHR and that an abrupt stop in exercise gives an "abstinence" reaction.