naloxone and Arterial-Occlusive-Diseases

Topics: Anticoagulants; Arterial Occlusive Diseases; Calcium Channel Blockers; Carotid Artery Diseases; Cerebral Infarction; Humans; Intracranial Embolism and Thrombosis; Naloxone

Recently, opioid receptors have been shown to be expressed on group III and IV afferents, which comprise the sensory arm of the exercise pressor reflex. Although the stimulation of opioid receptors in the central nervous system has been shown to attenuate the exercise pressor reflex, the effect on the reflex of their stimulation in the periphery is unknown. We therefore tested the hypothesis that the activation of peripheral mu-opioid receptors attenuates the exercise pressor reflex. The pressor responses to static contraction were compared before and after the injection of the mu-opioid receptor agonist [d-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO; 1 microg) into the abdominal aorta of decerebrated rats in which one femoral artery had been occluded 72 h previously (n = 10) and in control rats whose femoral arteries were freely perfused (n = 8). DAMGO attenuated the peak pressor response to contraction in rats whose femoral arteries had been occluded (before: increase of 34 + or - 3 mmHg and after: increase of 22 + or - 2 mmHg, P = 0.008); the inhibitory effect of DAMGO was prevented by the injection of naloxone (100 microg) into the abdominal aorta (before: increase of 29 + or - 5 mmHg and after: increase of 29 + or - 5 mmHg, P = 0.646, n = 7). An intravenous injection of DAMGO (1 microg, n = 6) had no effect on the peak pressor response to contraction in both groups of rats. DAMGO had no effect on the peak pressor response to contraction in rats whose femoral arteries were freely perfused (before: Delta 23 + or - 4 mmHg, after: Delta 23 + or - 3 mmHg, n = 6) but appeared to have a small effect on topography of the response. DAMGO had no effect on the peak pressor response to tendon stretch in both groups of rats (both P > 0.05). We conclude that the stimulation of peripheral mu-opioid receptors attenuates the exercise pressor reflex in rats whose femoral arteries have been ligated for 72 h.

Topics: Animals; Arterial Occlusive Diseases; Baroreflex; Chronic Disease; Constriction, Pathologic; Disease Models, Animal; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Femoral Artery; Hindlimb; Injections, Intra-Arterial; Injections, Intravenous; Ligation; Male; Muscle Contraction; Muscle, Skeletal; Naloxone; Narcotic Antagonists; Neurons, Afferent; Physical Exertion; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Time Factors

The authors examined the effect of the opiate antagonists naloxone and thyrotropin-releasing hormone (TRH) on neurological outcome and the size of areas of cerebral infarction in a rat model of focal cerebral ischemia. The middle cerebral artery (MCA) was permanently occluded in 66 adult Sprague-Dawley rats. The rats were randomly divided into three groups. In 20 Group I rats, TRH in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2 mg/kg/hr for 4 hours. In 20 Group II rats, naloxone in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2-mg/kg/hr for 4 hours. In 26 Group III rats, physiological saline was administered as an initial 0.5-cc bolus followed by continuous infusion of 0.5 cc/hr for 4 hours. All solutions were given in volumes of 0.5 cc for the bolus and 0.5 cc/hr for continuous infusion, and all infusions were begun within 10 minutes of MCA occlusion. Twenty-four hours after treatment, the rats underwent a careful neurological examination and were then sacrificed immediately. The size of areas of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride staining techniques. The neurological grade of the rats correlated with the size of infarcted areas among all grades, irrespective of treatment (p less than 0.01). Neither naloxone nor TRH improved neurological function or reduced the size of infarction compared to saline-treated control rats. Treatment with TRH caused a significant increase in mean arterial blood pressure during infusion, but naloxone had no effect. These results suggest that neither TRH nor naloxone are effective in the treatment of acute focal cerebral ischemia.

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Cerebral Arteries; Cerebral Infarction; Male; Naloxone; Narcotic Antagonists; Nervous System; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone

The effects of clonidine, a central alpha 2 agonist, on changes in blood pressure caused by muscle afferent nerve (ergoreceptor) activation and baroreceptor manipulation were studied in cats. Prolonged isometric contractions (ergoreceptor activation) of the gastrocnemius and plantaris muscles increased mean arterial pressure by 53 mmHg. This pressor response was not altered by naloxone (0.5 mumol.litre-1) but was eliminated by clonidine (0.5-2.0 micrograms) when injected into the cerebral aqueduct. Brief occlusion of the carotid artery (15-30 s) caused mean arterial pressure to increase by 32-42 mmHg at rest. Neither naloxone nor clonidine altered the magnitude of the reflex pressor response to carotid occlusion. Similar increases in pressure were measured when occlusion was applied during fatiguing isometric contractions; thus baroreceptor induced increases in pressure were superimposed on the ergoreceptor induced blood pressure changes. Naloxone did not affect the changes in pressure caused by either reflex response. Clonidine continued to eliminate the pressor response to muscular contraction but did not affect the pressure increase when the carotid occlusion was applied during contractions. Electrical stimulation of the carotid sinus nerve caused blood pressure to decrease by 36 mmHg during rest and by 41 mmHg during fatiguing isometric contractions. Clonidine did not alter the depressor response to carotid sinus nerve stimulation. These data may indicate that separate pathways centrally mediate the changes in blood pressure caused by ergoreceptor and baroreceptor afferent activation. The integration of the ergoreceptor pathway may involve a catecholaminergic-opioidergic system but the present results do not suggest a similar interaction for the baroreceptor integration.

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Carotid Artery Diseases; Cats; Clonidine; Isometric Contraction; Muscle Contraction; Naloxone; Pressoreceptors; Reflex

The effects of naloxone or thyrotropin releasing hormone (TRH) upon neurologic outcome were evaluated in gerbil models of cerebral ischemia. Following temporary bilateral carotid occlusion, hypotension was transiently reversed by these endorphin antagonists. However, neither drug altered time to awaken, time to death, or the severity of neurologic signs (ptosis, movement, retracted paws, circling, righting reflexes, seizures, or opisthotonus) when evaluated by a blinded rater. Hot plate escape and roto-rod performance were also unaltered by naloxone or TRH; TRH, but not naloxone, increased respiratory rates. Thus, the transient improvement of cardiorespiratory function produced by these drugs is unrelated to the morbidity and mortality associated with temporary cerebral ischemia in the gerbil. Additional studies evaluating the effects of naloxone or TRH upon neurologic outcome following permanent unilateral carotid occlusion also failed to show any therapeutic effects of these drugs. Both morphine and TRH exacerbated the effects of ischemia. Of gerbils which developed neurologic impairment, the deficit was usually ipsilateral to the occluded carotid. Collectively, these results indicate that neither naloxone nor TRH prevents ischemic deficits in the gerbil. Further studies with different cerebral ischemia models in other species are required to clarify the possible therapeutic effects of these drugs in experimental stroke.

Topics: Animals; Arterial Occlusive Diseases; Brain Ischemia; Carotid Artery Diseases; Disease Models, Animal; Gerbillinae; Male; Motor Activity; Naloxone; Thyrotropin-Releasing Hormone

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Cats; Myocardial Depressant Factor; Naloxone; Shock; Splanchnic Circulation