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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies by us established that dynorphin A-(1-8) concentration in the hippocampal formation of spontaneously hypertensive rat (SHR) brain was much less than in the hippocampus of normotensive controls. The connection between low dynorphins and SHR hypertension was unclear. The object of the present study was to determine (1) whether microinjections of dynorphin A-(1-8) into the hippocampus of anesthetized SHR would produce centrally mediated effects on arterial pressure and heart rate and (2) whether these responses would differ qualitatively or quantitatively from those elicited in normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats. A statistically significant elevation of arterial pressure was observed in SHR at 8, 12 and 16 weeks compared to WKY and Sprague-Dawley controls at similar ages. There were no significant changes in heart rate of SHR compared to WKY and Sprague-Dawley rats. Intra-hippocampal dynorphin A-(1-8) caused a dose-dependent (0.05, 0.5, 5.0 and 50.0 nmol) hypotension and bradycardia in all strains, and ages but the responses were quantitatively larger in SHR than in the normotensive strains. Nor-binaltorphimine, a selective antagonist for kappa-opioid receptor, pretreated into the hippocampus caused a significant blockade of the dynorphin A-(1-8) responses in all strains. The results established that (1) intra-hippocampal dynorphin A-(1-8) lowered the arterial pressure and heart rate by a central mechanism, in all strains, at all ages tested and (2) the responses were quantitatively greater in SHR than in WKY and Sprague-Dawley strains. The responses appear to involve activation of a kappa receptor in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular responses to intra-hippocampal dynorphin A-(1-8) in spontaneously hypertensive rats. 791 47

1. A comparison of the effects of various opioid peptides on the heart rates of self-paced right atria was made, as taken from spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats at 4, 8, 12 and 16 weeks of age. 2. Beta-endorphin, dynorphin, met-enkephalin, DAGO and DADLE slightly decreased the spontaneously beating rate of all rat strains and ages, at 0.1 microM. Leu-enkephalin at 0.2 microM increased the spontaneous beating rate of SHR atria, but not that of atria from normotensive strains. 3. SHR atria were somewhat more sensitive than WKY atria to norepinephrine (NE)-induced positive chronotropy, but the differences were not statistically significant. 4. In the presence of mu, delta or kappa opioid receptor agonists, SHR atrial sensitivity to NE-induced chronotropy was enhanced at all ages studied. By contrast, NE chronotropy was not significantly altered by the opioids in normotensive rat atria. 5. Based on the above results, all the three major opioid receptor subtypes (mu, delta and kappa) appear to be present in rat atria but the function of these receptors appears to be greater in SHR than in WKY and SD atria. 6. The results suggest a possible involvement of altered opioid responsiveness in atria during hypertension development in SHR but the nature of this involvement appears to be complex and is not readily understandable on the basis of the present study.
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PMID:Possible opioid receptor function changes in isolated atria of the spontaneously hypertensive rat. 811 24

The purpose of this study was to examine the roles of brain opioid receptors, using the opioid receptor antagonist naloxone, and brain alpha 2 adrenergic and imidazole receptors, using their agonist clonidine, in the hypertension and tachycardia induced by electrical stimulation of the AHA and PHA area. Unanesthetized and unrestrained Wistar rats 300-400 g that had previously had catheters inserted into the lateral cerebral ventricle and femoral artery and electrodes in AHA or PHA areas received intracerebral (ICV) administration of naloxone or clonidine prior to hypothalamic stimulation. AHA and PHA stimulation with current strength from 0.5 to 2.0 mA produced a significant (p < 0.05) and dose dependent increase in BP and heart rate. Naloxone reduced the increase in BP with AHA stimulation at all but the highest stimulation current intensity. Clonidine also blunted the BP increase to AHA stimulation but to a lesser degree than naloxone. The combination of both naloxone and clonidine completely prevented the increase in BP even at high current intensities. Both naloxone and clonidine prevented the increase in heart rate with AHA stimulation. In contrast to AHA stimulation, naloxone did not alter the BP increase produced by PHA stimulation while clonidine prevented the effects of PHA stimulation. Heart rate did not increase with PHA stimulation. These data suggest that (i) the mechanisms involved in the hypertensive response to AHA are different from that of PHA. (ii) the endogenous opioid system is more operative in mediating the BP elevation produced by AHA but not PHA stimulation (iii) activation of the central alpha adrenergic or imidazole receptors can suppress hypertensive response to both AHA and PHA but is more effective for PHA than AHA stimulation.
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PMID:Comparative effects of central administration of naloxone and clonidine on the blood pressure and heart rate response to anterior and posterior hypothalamic stimulation. 817 7

Remifentanil is a mu-opioid receptor agonist with a context sensitive half-time of 3 min and an elimination half-life < or = 10 min. This study sought to evaluate the efficacy of remifentanil and propofol total intravenous anesthesia (TIVA) in 161 patients undergoing inpatient surgery. Remifentanil 1 microgram/kg was given intravenously (i.v.) followed by one of two randomized infusion rates: small dose (0.5 micrograms.kg-1.min-1) or large dose (1 microgram.kg-1.min-1). Propofol (0.5-1.0 mg/kg i.v. bolus and 75 micrograms.kg-1.min-1 infusion) and vecuronium were also given. Remifentanil infusions were decreased by 50% after tracheal intubation. End points included responses (hypertension, tachycardia, and somatic responses) to tracheal intubation and surgery. More patients in the small-dose than in the large-dose group responded to tracheal intubation with hypertension and/or tachycardia (25% vs 6%; P = 0.003) but there were no other differences between groups in intraoperative responses. Recovery from anesthesia was within 3-7 min in both groups. The most frequent adverse events were hypotension (systolic blood pressure [BP] < 80 mm Hg or mean BP < 60 mm Hg) during anesthesia induction (10% small-dose versus 15% large-dose group; P = not significant [NS]) and hypotension (27% small-dose versus 30% large-dose group; P = NS), and bradycardia (7% small-dose versus 19% large-dose group; P = NS) during maintenance. In conclusion, when combined with propofol 75 micrograms.kg-1.min-1, remifentanil 1 microgram/kg i.v. as a bolus followed by an infusion of 1.0 microgram.kg-1.min-1 effectively controls responses to tracheal intubation. After tracheal intubation, remifentanil 0.25-4.0 micrograms.kg-1.min-1 effectively controlled intraoperative responses while allowing for rapid emergence from anesthesia.
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PMID:A multicenter evaluation of total intravenous anesthesia with remifentanil and propofol for elective inpatient surgery. 869 6

Tramadol is a centrally acting analgesic that has been shown to be effective in a variety of acute and chronic pain states. Unlike other centrally acting analgesics, it exerts a dual action by binding to the opioid receptor site in the central nervous system and by weakly inhibiting the reuptake of biogenic amines. Tramadol is rapidly and almost completely absorbed, with an onset of action occurring within 1 hour of oral administration. The recommended dosage is 50 to 100 mg every 4 to 6 hours; however, regular administration is an alternative, particularly for chronic pain states such as osteoarthritis, where the use of the recently developed sustained release formulation may represent an important advantage. Published studies specifically evaluating the use of tramadol in this disease support its effectiveness. Nausea, drowsiness, constipation, dizziness, and sweating have been reported in association with tramadol use. Nausea occurs early in the course of administration, and may be reduced by slowly titrating the dose of tramadol against response. Tramadol would appear to be particularly useful in the elderly population affected by osteoarthritis because, unlike nonsteroidal anti-inflammatory drugs, it does not aggravate hypertension or congestive heart failure, nor does it have the potential to cause peptic ulcer disease. Compared with narcotics, tramadol does not induce significant respiratory depression, constipation, or have significant abuse potential.
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PMID:Pharmacology and clinical experience with tramadol in osteoarthritis. 891 98

1. The central cardiovascular effects of several opioid receptor selective agonists and the nonselective opioid antagonist, naloxone, were studied in anesthetized normotensive control rats, in spontaneously hypertensive rats (SHR), and in foot-shock-stressed rats. 2. Receptor-selective agonists injected into the rostral ventrolateral medulla (RVLM), paraventricular nucleus (PVN), and dorsal hippocampus (dHip) were DAGO (mu), DADLE (delta), and U50,488H (kappa). 3. DAGO and DADLE (3 nM) decreased arterial pressure and heart rate in RVLM and PVN of all rat strains, while U-50,488H (9 nM) had only minimal effects in these areas. 4. In dHip, only DADLE (3 nM) had depressor and bradycardic effects, and then, only in SHR, with DAGO and U50,488H being ineffective in any strain, even at 9 nM. 5. Prior injection of naloxone (10 nM) into the RVLM, PVN and dHip blocked and postinjection reversed the cardiovascular effects of the agonists. Naloxone alone increased blood pressure and heart rate in all three areas, in all rat strains except SHR, suggesting a tonic depressor effect of endogenous opioids. 6. Lack of significant quantitative differences in opioid agonist and antagonist effects between normotensive and hypertensive or stressed rats argues against a role for endogenous brain opioids in experimental hypertension.
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PMID:Central effects of opioid agonists and naloxone on blood pressure and heart rate in normotensive and hypertensive rats. 898 Oct 66

The present study was undertaken to characterize the mechanisms of the hemodynamic responses to microinjection of the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) into the paraventricular nucleus of the hypothalamus, in conscious rats chronically instrumented with pulsed Doppler flow probes. We found that i.v. pretreatment with phentolamine had no effect on the tachycardia elicited by DAMGO (1 nmol); however, the pressor response was reversed to a state of hypotension, the renal and superior mesenteric vasoconstrictions were attenuated and the hindquarter vasodilation was potentiated. In the presence of propranolol, the pressor response and renal vasoconstriction were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarter vasodilation was abolished. Moreover, in those animals we observed bradycardia followed by tachycardia. Combined i.v. pretreatment with phentolamine and propranolol abolished the pressor and heart rate responses to DAMGO but had no effect on the renal and superior mesenteric vasoconstrictions, although the hindquarter vasodilation was reduced. Intravenous pretreatment with a vasopressin V1 receptor antagonist or captopril had no effect on the cardiovascular responses to DAMGO. Together, these results indicate that the hypertension observed after injection of DAMGO into the paraventricular nucleus of the hypothalamus was secondary to alpha adrenoceptor-mediated vasoconstrictions in renal and superior mesenteric vascular beds and to beta adrenoceptor-mediated vasodilation in the hindquarter vascular bed, whereas the involvement of circulating vasopressin or angiotensin seems less obvious from the present findings. However, we cannot exclude the possibility that nonadrenergic, nonvasopressinergic and nonangiotensinergic vasoconstrictor mechanisms were acting in the renal and superior mesenteric vascular beds.
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PMID:Mechanisms of the regional hemodynamic effects of a mu-opioid receptor agonist microinjected into the hypothalamic paraventricular nuclei of conscious unrestrained rats. 899 29

1. The modulatory actions of both adenosine A1 and kappa 1-opioid receptor agonists on beta-adrenoceptor stimulation in the heart of both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. 2. In both types of rats, both R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), an adenosine A1 receptor agonist, and U50 488H, a kappa 1-opioid receptor agonist, inhibited the stimulatory effects of beta-adrenoceptor activation on electrically induced [Ca2+]i transients measured by a spectrofluorometric method with fura-2/AM as the calcium indicator. The effects of these two agonists were blocked by their respective antagonists, namely 8-cyclopentyl-1,3-diprolxanthine and norbinaltorphimine. 3. The inhibitory actions of both R-PIA and U50 488H on beta-adrenoceptor augmentation of electrically induced [Ca2+]i transients in the heart were more significantly reduced in SHR than in WKY rats, suggesting the negative modulatory actions of endogenous substances on beta-adrenoceptors were impaired in SHR, which may contribute to hypertension.
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PMID:Reduced inhibitory actions of adenosine A1 and kappa 1-opioid receptor agonists on beta-adrenoceptors in spontaneously hypertensive rat heart. 940 69

It has recently been reported that kappa-opioid receptor agonists inhibit antidiuretic hormone secretion and promote water excretion in humans and animals. We investigated the effect of niravoline (RU 51599), a selective kappa-opioid receptor agonist in the treatment of intracranial hypertension. Acute intracranial hypertension was induced in cats by continuous inflation of an extradural balloon with physiological saline at the constant rate of 0.5 ml/h for 3 h. At this point, inflation was discontinued and the balloon remained expanded for an additional hour after which it was deflated. In the post-deflation period, monitoring continued for 1 h. The control group (n = 8) received ringer's lactate solution only, while the treatment group (n = 8) received an intravenous (IV) injection of 1.0 mg/kg of niravoline, every hour at the beginning of balloon inflation, during balloon inflation, in post-inflation, and at deflation time (5 doses). Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), electroencephalogram (EEG), blood gases, pupil size, serum electrolytes, and osmolality were measured in both groups. Brain water content was determined in a separate group of cats at the end of a 3-h extradural brain compression. Compared to the untreated group, the niravoline-treated group had a significantly lower ICP and higher CPP at the 2 and 3 h during balloon inflation, in post-inflation, and in post-deflation periods. Brain water content was significantly reduced in niravoline-treated animals. No significant change was observed in serum osmolality throughout the experiment. Our results indicate that the mechanism by which niravoline reduces ICP is partly via a reduction in brain water content. Also, the current findings suggest that in clinical situations in which ICP is elevated due to the pressure of an extradural mass, niravoline may effectively reduce ICP while maintaining adequate CPP until the mass is removed.
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PMID:Effects of niravoline (RU 51599), a selective kappa-opioid receptor agonist on intracranial pressure in gradually expanding extradural mass lesion. 951 87

The kappa-opioid receptor exerts a negative modulatory action on the beta-adrenoceptor and the action is blunted in adult spontaneously hypertensive rats (SHR). In order to determine whether the blunted negative modulation of the beta-adrenoceptor by the kappa-opioid receptor contributes to the development of hypertension, the electrically induced intracellular calcium ([Ca2+]i) transient was measured in single ventricular myocytes of SHR at 4, 6, 8 and 13-week-old and the age-matched Wistar Kyoto (WKY) rats. The electrically induced [Ca2+]i transients were augmented by norepinephrine (NE), a beta-adrenoceptor agonist, over four-fold in WKY rats of all ages studied and in SHR of 4 and 6 weeks of age. The enhancing effect of NE in 8- and 13-week-old SHR was, however, only approximately three-fold, significantly lower than the corresponding values in age-matched WKY rats. Similarly, the electrically induced [Ca2+]i transients were also augmented by forskolin, an activator of adenylate cyclase, by approximately two-fold in WKY rats of all ages and SHR aged 4 and 6 weeks. In SHR aged 8 and 13 weeks, the effect of forskolin was only 1.5-fold, significantly lower than the two-fold increase in the corresponding WKY rats. The enhancing effects of NE and forskolin were attenuated by U50,488H, a selective kappa-opioid agonist, by approximately 50 and 25%, respectively, in both types of rats of all ages studied, with the exception of 13-week-old rats. In rats of this age group, the attenuations by U50,488H on the enhancing effects of NE and forskolin were 17 and 9% in SHR, respectively, significantly less than the corresponding 54 and 29% in WKY. The fact that attenuation of U50,488H on the enhancing effects of NE and forskolin only occurs in 13-week-old SHR when hypertension has been fully developed indicates that the attenuated inhibitory modulation of kappa-opioid receptor stimulation does not contribute to the initiation of hypertension. Interestingly, the enhancing effects of NE and forskolin on the electrically induced [Ca2+]i transient was attenuated in SHR aged from 8 weeks when the blood pressure was rapidly increasing. The different time courses of altered responses to U50,488H, and NE and forskolin suggest that the attenuated negative modulation of kappa-receptor stimulation on the beta-adrenergic receptor is not due to the signal transduction pathway activated by beta-adrenergic stimulation. In 13-week-old SHR with the arterial blood pressure restored to normal by pharmacological manipulations, the blunted responses to NE, U50,488H and forskolin still occurred, indicating that the altered responses to activation of beta-adrenergic and kappa-opioid receptors and adenylate cyclase are not secondary to hypertension.
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PMID:Cross-talk between cardiac kappa-opioid and beta-adrenergic receptors in developing hypertensive rats. 1019 90


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