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

Experiments were conducted to test the hypothesis that chronic administration of an opioid receptor antagonist, naloxone, would affect the outcome of the developmental phase of hypertension in Dahl salt-sensitive (S/JR strain) rats. Accordingly, S/JR rats were maintained on either a low-salt (0.45% NaCl) or a high-salt (7% NaCl) diet for 4 wk. Half of the animals of each dietary group were treated with naloxone (100-130 micrograms/h) by osmotic minipump. Food and water intakes of the high-salt animals were measured for the first 25 days, and blood pressure was measured at the end of the 4 wk via an indwelling femoral arterial catheter. Naloxone treatment slightly but significantly reduced the level of hypertension attained in the high-salt animals (158 +/- 2 mmHg in naloxone-treated animals vs. 168 +/- 3 mmHg in control animals; P less than 0.05) and also attenuated food (and hence salt) and water intakes. Naloxone did not affect the blood pressure of the low-salt animals. To determine whether the slight attenuation of hypertension might be secondary to a reduction of salt intake, a group of control S/JR animals were fed a moderately high-salt diet (2% NaCl), and naloxone-treated S/JR animals were salt-intake matched to this group by daily adjustment of the dietary salt content. Blood pressures after 4 wk of treatment were not different between these two groups. Finally, acute administration of 1 and 30 mg/kg of naloxone failed to lower blood pressure of animals with established hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of naloxone on hypertension in Dahl salt-sensitive rats. 173 7

1. The effects of three opioid receptor agonists on the blood pressure and heart rate of anaesthetized normotensive, spontaneously hypertensive and renal hypertensive rats were measured. 2. Mu agonist morphiceptin i.c.v. induced a pressor response and increase in heart rate in hypertensive rats, but hypotension in normotensive rats. After intravenous (i.v.) injection, morphiceptin produced a hypotensive response in all three groups of rats. 3. In contrast, the delta agonist DTLET i.c.v. decreased blood pressure and heart rate in hypertensive rats, but increased both pressure and beat rate in normotensive rats. After i.v. injections DTLET produced a hypertensive response and increase in heart rate in all groups of rats. 4. Kappa agonist U-50, 488H given i.c.v. induced effects similar to morphiceptin: an increase in blood pressure and heart rate in hypertensive and a decrease in normotensive rats. After i.v. injections U-50, 488H produced decreases in blood pressure and heart rate in all treated groups of rats. 5. Pretreatment with naloxone antagonized the activity of morphiceptin but prevented only the stimulating effect of DTLET in normotensive rats. Cardiovascular actions of U-50, 488H were not blocked by naloxone. 6. The results suggest that opioid agonists exert similar changes in cardiovascular function at central and peripheral sites in both models of experimental hypertension and these effects are different in normotensive rats.
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PMID:Normotensive Wistar rats differ from spontaneously hypertensive and renal hypertensive rats in their cardiovascular responses to opioid agonists. 179 45

The aims of the present study were to examine the effects of opioid receptor agonists and antagonists on the renal vascular (renal blood flow) and tubular (urinary sodium excretion) responses to renal nerve stimulation and norepinephrine in anesthetized spontaneously hypertensive rats (SHR). Graded frequency renal nerve stimulation (0.5-4.0 Hz) and doses of norepinephrine (10-80 ng/kg) produced frequency and dose-dependent decreases in renal blood flow. The renal vasoconstrictor responses were not altered by intravenous infusion of the opioid receptor agonists methionine enkephalin (mu and delta, 75 micrograms/kg/min) or U-50488H (kappa, 20 micrograms/kg/min) or administration of the opioid receptor antagonist naloxone (1 mg/kg i.v.). The antinatriuretic response to low frequency (less than 1.0 Hz) electrical renal nerve stimulation was prevented by naloxone but not affected by methionine enkephalin administration without changes in glomerular filtration rate or effective renal plasma flow. These studies suggest that endogenous opioid receptor mechanisms are involved in the increased renal tubular sodium reabsorption response to low frequency renal nerve stimulation but not in the renal vasoconstrictor response to either renal nerve stimulation or norepinephrine. This might occur by facilitation of the renal nerve terminal release, the direct renal tubular action, or both, of norepinephrine to influence renal tubular sodium reabsorption.
Hypertension 1990 Jun
PMID:Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats. 235 29

Intravenous administration of the opioid receptor antagonist naloxone to asphyxiated fetal sheep increases the arterial blood pressure. We examined the hypothesis that endogenous opioids modify the cardiac output distribution during asphyxia due to changes in the vascular resistance of some fetal organs. Thirteen fetal sheep (0.8-0.9 of gestation) were chronically catheterized. Fetal asphyxia was induced by reducing the uterine blood flow with an inflatable occluder around the common internal iliac artery to approximately 50% of control for 40 min. Naloxone solution or the solvent alone was added for the last 20 min. Asphyxia caused hypertension, and the fetal arterial blood pressure further increased when asphyxiated fetuses received naloxone. Heart, brain, and adrenal blood flows increased due to the increase in blood pressure, with no changes in their vascular resistances. In contrast, kidney and carcass blood flows decreased, and their vascular resistances increased. We conclude that endogenous opioids inhibit the vasoconstriction of these vascular beds during fetal asphyxia.
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PMID:Role of endogenous opioids in the cardiovascular responses to asphyxia in fetal sheep. 271 49

Endogenous opioid peptides have been implicated in the regulation of cardiovascular and renal function. We tested this hypothesis by examining whether the opioid antagonist naloxone alters the cardiovascular or renal responses produced by environmental stress (air stress) in conscious spontaneously hypertensive rats (SHR). Before naloxone administration, air stress produced significant increases in heart rate, mean arterial pressure, and renal sympathetic nerve activity, and it caused a decrease in urinary sodium excretion. After intravenous and intracerebroventricular administration of naloxone, the air stress-induced pressor and antinatriuretic responses were inhibited. Subsequent studies with a different opioid antagonist, the quaternary compound naltrexone methylbromide, also showed inhibition of the air stress-induced pressor and antinatriuretic responses and demonstrated opioid receptor specificity of this inhibition. Furthermore, since only intracerebroventricular and not intravenous administration of naltrexone methylbromide inhibited the pressor and antinatriuretic responses to air stress, a central nervous system site of action was established. The opioid antagonists caused inhibition of the pressor and antinatriuretic responses to air stress without affecting the air stress-induced increase in renal sympathetic nerve activity. Our investigations indicate that central endogenous opioid peptides contribute to the pressor and antinatriuretic responses that occur in conscious SHR during acute environmental stress.
Hypertension 1989 Jun
PMID:Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats. 273 20

Opiates, like morphine, were long known to produce changes in blood pressure and cardiac functions. However, the nature of these changes are a subject of continuous controversy. The substantial differences in the opiate effects on the cardiovascular system is also apparent in more recent studies using enkephalins, beta-endorphin and dynorphins. The present review is aimed to indicate the source of the variations in the experimental data and analyze the relative contribution of different experimental factors to the observed effects of opiates and opioid peptides on the cardiovascular system. The major factors which contribute to the nature of the opioid effect on the cardiovascular system are: anesthesia, species, dose, site of action in the brain, respiratory changes and receptor specificity. However, the cardiovascular status per se is an important determinant of the opiates and opioid peptide effects on hemodynamic functions as indicated in states of hypertension and shock. A newly described factor is the plasticity of the opioid receptor system which changes its level and distribution pattern in different physiological and pathophysiological states. This review emphasizes the importance of utilization of highly specific ligands to opiate receptors administered to discrete brain areas in the conscious animal.
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PMID:The opioid system and central cardiovascular control: analysis of controversies. 300 75

This review is an attempt to highlight evidence that may implicate the endogenous opioid system in the pathogenesis of hypertension in humans. The evidence raised includes biochemical, physiological, pharmacological, and behavioral studies conducted in in vitro and in vivo systems, experimental models of hypertension, and humans with essential hypertension. While the compelling biochemical and pharmacological evidence in experimental animals clearly shows the presence of opioid peptides and their receptors in strategic sites of cardiovascular control and potent cardiovascular response to opioid peptides, opioid antagonists show no consistent blockade or reversal of hypertension in experimental animals or humans. One possible explanation for this phenomenon could be the vast redundancy in systems regulating blood pressure (i.e., the blockade of one system still leaves many other systems fully able to rapidly offset the eliminated system). Regarding the opioid system, the situation is much more complex, since some opioid receptors (mu-type) mediate pressor responses, while other receptors (kappa-type) mediate depressor responses. Therefore, nonselective opioid receptor antagonists (e.g., naloxone), which block both types of receptors, can be devoid of any cardiovascular activity, while a selective mu-receptor antagonist or a selective and potent kappa-receptor agonist may produce the desired antihypertensive effect. A combination of both actions (i.e., a drug that is both a mu-antagonist and a kappa-agonist) might be even more advantageous. Until such compounds are developed, this hypothesis will be hard to prove.
Hypertension 1987 Jun
PMID:The opioid peptides. A role in hypertension? 329 91

In this study a possible relationship between regulatory mechanisms involved in pain and blood pressure control has been investigated in the rat. Spontaneously hypertensive rats (SHR), their normotensive Wistar-Kyoto (WKY) controls, and two experimental models of hypertension together with their appropriate sham-operated controls were tested for their responsiveness to pain. Two methods for measurement of nociceptive responsiveness (hot plate and electric footshock threshold) were used. A diminished responsiveness was observed in both young (still normotensive) and adult (hypertensive) SHR. Pretreatment with naloxone reduced hot plate response times of adult SHR to the level of WKY, indicating opioid receptor involvement. Despite severe hypertension in rats with a renal artery clip and in DOCA-salt treated rats, no reduction of pain sensitivity as compared to sham-operated controls was evident in the hypertensive rats as assessed by both methods. It is concluded, that the higher pain threshold in SHR is probably determined by genetic factors rather than hypertension.
Hypertension
PMID:Hypoalgesia in genetically hypertensive rats (SHR) is absent in rats with experimental hypertension. 682 14

Arterial hypertension induced by microinjections of N-methyl-D-aspartate (NMDA) (2 nmol/rat) into the midbrain periaqueductal gray matter was used to assess the involvement of opioid receptors (mu, delta and kappa) in modulating pressor periaqueductal gray neurons. Groups (n = 5-8) of urethane-anaesthetised rats received, 5 min before NMDA, microinjections of selective opioid receptor antagonists in the periaqueductal gray area and arterial blood pressure was monitored. Pretreatments with naloxone (5 nmol/rat), a non selective mu receptor antagonist, or naltrindole hydrochloride (5 nmol/rat), a selective delta receptor antagonist, significantly (P < 0.05) decreased by 31% and 37%, respectively, NMDA-induced hypertension. The latency for the maximum increase of NMDA-induced hypertension was also significantly (P < 0.05) increased with naloxone. Pretreatment with nor-binaltorphimine (5 nmol/rat), a selective kappa receptor antagonist, only increased the latency of NMDA-induced hypertension. Each opioid antagonist failed per se to alter arterial blood pressure. Microinjection of morphine (13 nmol/rat), a non selective mu receptor agonist, significantly decreased (P < 0.05) by 57.5% NMDA-induced arterial hypertension and this effect was antagonised by naloxone. Combined pretreatments in the periaqueductal gray area with naloxone and the GABAA antagonist bicuculline (2.5 nmol/rat; 5 min before naloxone) antagonised the effect of naloxone on NMDA-induced hypertension. In contrast, bicuculline significantly (P < 0.05) potentiated morphine-induced decrease of NMDA hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of opioid receptors in N-methyl-D-aspartate-induced arterial hypertension in periaqueductal gray matter. 771 45

To determine whether the peripheral opioid system participates in hypertension development we studied responses to various opioid receptor agonists in field-stimulated isolated tail artery segments taken from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats at different ages. The mu-selective agonist (DAGO) and the delta-selective D-Ala2-D-Leu5-enkephalin (DADLE) both suppressed the electrically stimulated vasoconstriction (EIC), but only in SHR arteries. The mu-selective antagonist beta-funaltrexamine reversed the effects of both DAGO and DADLE. Since the delta-selective antagonist ICI-174864 did not block DADLE inhibition, it is likely that both DAGO and DADLE effects were mu-receptor-mediated. Effects of DAGO and DADLE were qualitatively and quantitatively similar at all ages of SHR tested, and were not temporally related to hypertension development. Dynorphin (1-13) (DYN), a kappa-agonist, increased basal tone and EIC in all three rat strains. These responses were not blocked by nor-binaltorphimine, a selective kappa-opioid antagonist, suggesting that they may not involve kappa-receptor activation. There was a greater sensitivity to DYN at younger ages in all three rat strains and the sensitivity decreased with age. At 16 weeks when SHR hypertension was fully developed, SHR tail artery became almost totally insensitive to DYN in contrast to the continued responsiveness of 16-week-old WKY and SD arteries. The diminished effects to DYN in 16-week-old SHR tail arteries is suggestive of a compensatory mechanism to the hypertensive state. Collectively, the results establish that opioid receptor responses in SHR tail artery differ from those of normotensive rats. The significance of these differences to hypertension development in SHR remains to be determined.
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PMID:Influence of hypertension development on rat tail artery responses to opioid peptides. 789 79


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