Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rapid fall in blood pressure after removal of the constricting clip in two-kidney one-clip (2K-1C) hypertension in the rat is not fully explained by inhibition of the renin-angiotensin system or change in sodium balance. It has been postulated that compounds released in the renal venous effluent following unclipping of 2K-1C rats have a central opiate-like action and endogenous opioids are recognized to have profound hypotensive properties. To investigate this, we removed the clip from, or performed a sham operation in, early phase (less than 6 weeks) 2K-1C hypertensive rats during an infusion of naloxone, an opioid antagonist, or vehicle alone. The infusion of naloxone did not affect the pattern of blood pressure fall in either unclipped or sham-operated rats. Both naloxone-treated and control groups were similarly normotensive at 24 hr postoperation, the MAP being significantly lower than in the sham-operated groups, which regained previously hypertensive levels. Heart rate was unchanged 24 hr postoperatively in all groups. Morphine-induced bradycardia and hypotension were significantly reduced by naloxone infusion. Thus, naloxone infusion had no effect on blood pressure or heart rate in either the sham-operated or the unclipped groups, indicating that endogenous opioids do not have a major role in the reversal of renovascular hypertension under these circumstances.
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PMID:Failure of naloxone to influence surgical reversal of two-kidney, one-clip hypertension in the rat. 354 Sep 75

Two different patterns of response to a pressor stimulus occurred in conscious rabbits. This difference was not apparent when a depressor stimulus was applied. At levels of mean arterial pressure exceeding 120 mmHg one group of animals exhibited a marked bradycardia which was due to sympathetic inhibition in addition to vagal activation while this sympathetic component appeared to be lacking in the second group of animals. Naloxone (0.1 mg/kg i.v.) markedly reduced the sympathetic inhibition elicited by phenylephrine but had no significant effect on the reflex vagal stimulation. Naloxone thereby abolished the difference in sensitivity of baroreflex control of heart rate in response to a pressor stimulus between the two groups of rabbits. Naloxone did not influence the sensitivity of the reflex response to nitroprusside. Morphine (2 mg/kg) increased the vagal component of the baroreceptor reflex in response to a pressor stimulus and the sensitivity of the reflex response to nitroprusside in all the rabbits, and this was antagonized by naloxone (0.1 mg/kg). Morphine also potentiated and naloxone antagonized the bradycardic response at levels of MAP exceeding 120 mmHg, in those rabbits which appeared to lack the cardiac sympathetic inhibitory component of the reflex. The results show that endogenous and exogenous opiates can increase the reflex bradycardia in response to a pressor stimulus in the conscious rabbit. The difference in baroreflex sensitivity in different animals may result from their varying ability to activate endogenous opioid systems which depress cardiac sympathetic activity.
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PMID:Endogenous opiates mediate cardiac sympathetic inhibition in response to a pressor stimulus in rabbits. 652 4

The antinociceptive efficacy of different opioid-receptor agonists following their intrathecal (i.t.) administration was examined in awake, unanesthetized rats in a model of visceral pain. Cumulative i.t. doses of the mu-preferring opioid-receptor agonist morphine produced dose-dependent attenuation of the change (increase) in mean arterial pressure (delta MAP) and elevation of the visceromotor threshold to colorectal distension (CRD). Similar dose-dependent antinociceptive effects were produced after i.t. administration of the mu opioid-receptor-selective agonist DAMPGO. Morphine and DAMPGO were equipotent against the delta MAP to phasic CRD (80 mm Hg, 20 sec), but DAMPGO was more than 6 times more potent than morphine in elevating the visceromotor threshold to an incrementing CRD. Intrathecal administration of the delta opioid-receptor-selective agonist DPDPE produced, like morphine and DAMPGO, a dose-dependent attenuation of the delta MAP to CRD; DPDPE was one-tenth as potent as morphine or DAMPGO. DPDPE also dose-dependently elevated the visceromotor threshold to CRD, but its efficacy was only half that of morphine or DAMPGO. The kappa opioid-receptor-selective agonist U 50488H was without antinociceptive efficacy after i.t. administration, but did attenuate responses to CRD after systemic administration. The antinociceptive effects produced by morphine and DAMPGO were antagonized by i.t. pretreatment with naloxone and the effects produced by DPDPE were antagonized by i.t. pretreatment with the delta opioid-receptor-selective antagonist naltrindole. These data indicate that local mu and delta, but not kappa, opioid receptors can modulate visceral nociceptive transmission in the spinal cord.
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PMID:Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat. 857 89

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.
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PMID:Effect of morphine on sympathetic nerve activity in humans. 1238 64