Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat

Quock, Raymond M.; Kouchich, F. J.; Vaughn, Linda K.; Friès, D

doi:10.1016/0024-3205(85)90516-8

Cited by 13 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In unanesthesized dogs, intravenous adminstration of naltrexone (1-80 pg/kg) has been reported to have no effect on blood pressure, respiratory rate, arterial blood gases and EEG, although slight bradycardia (maxi mum 25%) was found at the highest doses [29]. In normotensive rats, naltrexone does not appear to effect blood pressure, although dose-dependent decreases in HR have been found using high doses of naltrexone (10-15 mg/kg) administered intravenously [30]. However, in situations in which opioid pep tides are mobilized such as in septic or hypo volemic shock, opiate antagonists have been found to significantly reverse the hypoten sion associated with these conditions in both rats [21] and humans [31,32], Also, in cer tain genetic conditions in which opioids may be elevated such as in spontaneous hyperten sion in rats, there is evidence that naltrexone can significantly reduce blood pressure [30].…”

Section: Discussionmentioning

confidence: 94%

“…In normotensive rats, naltrexone does not appear to effect blood pressure, although dose-dependent decreases in HR have been found using high doses of naltrexone (10-15 mg/kg) administered intravenously [30]. However, in situations in which opioid pep tides are mobilized such as in septic or hypo volemic shock, opiate antagonists have been found to significantly reverse the hypoten sion associated with these conditions in both rats [21] and humans [31,32], Also, in cer tain genetic conditions in which opioids may be elevated such as in spontaneous hyperten sion in rats, there is evidence that naltrexone can significantly reduce blood pressure [30]. In summary, these data suggest that the car diovascular effects of acutely administered naltrexone in an unchallenged child, adult or animal are nonsignificant or minimal, al though additional data will be needed to determine the reliability of this conclusion.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Acute Administration of Naltrexone on Cardiovascular Function, Body Temperature, Body Weight and Serum Concentrations of Liver Enzymes in Autistic Children

Herman¹,

Hammock²,

Arthur-Smith³

et al. 1989

Dev Pharmacol Ther

View full text Add to dashboard Cite

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Effects of Acute Administration of Naltrexone on Cardiovascular Function, Body Temperature, Body Weight and Serum Concentrations of Liver Enzymes in Autistic Children

Herman¹,

Hammock²,

Arthur-Smith³

et al. 1989

Dev Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…44 Intravenous infusion of the opioid antagonists naloxone and naltrexone was shown to produce transient decreases in blood pressure and heart rate in SHR but not in WKY. 45 However, in several other studies conducted in normotensive or hypertensive animals, naloxone had no effect on blood pressure. 3046 Also, infusion of naloxone over 2 weeks to young SHR failed to prevent the development of hypertension.…”

Section: Pharmacological Evidencementioning

confidence: 93%

The opioid peptides. A role in hypertension?

Feuerstein¹,

Sirén²

1987

Hypertension

View full text Add to dashboard Cite

SUMMARY 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 (/x-type) mediate pressor responses, while other receptors (K-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 /x-receptor antagonist or a selective and potent K-receptor agonist may produce the desired antihypertensive effect. A combination of both actions (i.e., a drug that is both â -antagonist and a K-agonist) might be even more advantageous. Until such compounds are developed, this hypothesis will be hard to prove. (Hypertension 9: 561-565, 1987) KEY WORDS • /n-opioid receptors vascular resistance K-opioid receptors • naloxone • blood pressure N UMEROUS neurally localized peptides are now known to exist within the central nervous system (CNS). Many of these peptides originally were found in the hypothalamus and pituitary gland and later were shown to be widely distributed in the CNS and to possess diverse autonomic functions through modulation of sympathetic and parasympathetic tone and the baroreceptor reflex mechanism.Neuropeptides like vasopressin, angiotensin, bradykinin, neurokihins (e.g., substance P and thyrotropinreleasing hormone) have long been a subject of discussions in reference to cardiovascular regulation. The

show abstract

“…In SH R rats, low doses of D A M G O produce pressor effects when in jected into the hypothalamic nucleus preopti cus medialis [5], D A M G O causes pressor re sponse when microinjected into nucleus ambiguus [6], The effects of opiate antagonists, naloxone and naltrexone on blood pressure have also been determined. Whereas in con scious squirrel monkeys, intravenous injec tions of naloxone or naltrexone (0.3-10 mg/kg) failed to affect blood pressure or heart rate [7], both agents in high doses produced a brief, dose-related decrease in mean arterial pressure of urethane-anesthetized SH R rats, but had no effect in W K Y rats [8], These effects of antagonists were suggested to be centrally mediated since quaternary com pounds which cross the blood-brain barrier with difficulty were ineffective. Since high doses were required making the actions non specific, it was suggested that the effects were not due to p-opiate receptors [8] [1,8].…”

Section: Introductionmentioning

confidence: 99%

“…Whereas in con scious squirrel monkeys, intravenous injec tions of naloxone or naltrexone (0.3-10 mg/kg) failed to affect blood pressure or heart rate [7], both agents in high doses produced a brief, dose-related decrease in mean arterial pressure of urethane-anesthetized SH R rats, but had no effect in W K Y rats [8], These effects of antagonists were suggested to be centrally mediated since quaternary com pounds which cross the blood-brain barrier with difficulty were ineffective. Since high doses were required making the actions non specific, it was suggested that the effects were not due to p-opiate receptors [8] [1,8]. The distribution for 3H -D A M G O binding sites in brain regions was different and so was the affinity of the ligand.…”

Section: Introductionmentioning

confidence: 99%

Binding of 3H-D-Pen2-D-Pen5-Enkephalin to Brain Regions and Spinal Cord Membranes of Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats

Bhargava

Rahmani²

1993

Pharmacology

View full text Add to dashboard Cite

The binding of ³H-D-Pen²-D-Pen⁵-enkephalin (DPDPE), a highly selective δ-opiate receptor agonist, to membranes of discrete brain regions and spinal cord of 10-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were amygdala, hippocampus, hypothalamus, pons and medulla, corpus striatum, midbrain and cortex. ³H-DPDPE bound to membranes of brain regions and spinal cord at a single high affinity site with apparent dissociation constant value of 4 nmol/l, except in cortex where the values were higher. The highest density of ³H-DPDPE binding sites were in hypothalamus and lowest in pons and medulla. The receptor density (B_max value) and apparent dissociation constant (K_d value) of ³H-DPDPE to bind to δ-opiate receptors on the membranes of hippocampus, hypothalamus, corpus striatum, midbrain, cortex, pons and medulla and spinal cord of WKY and SHR rats did not differ. The B_max value of ³H-DPDPE in amygdala of SHR rats was higher than in WKY rats, but the K_d values in the two strains did not differ. It is concluded that SHR rats have a higher density of δ-opiate receptors, labeled with ³H-DPDPE, in amygdala in comparison with WKY rats. Whether such a difference in the density of δ-opiate receptors is related to the elevated blood pressure of SHR rats is not clear.

show abstract

Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat

Cited by 13 publications

References 33 publications

Effects of Acute Administration of Naltrexone on Cardiovascular Function, Body Temperature, Body Weight and Serum Concentrations of Liver Enzymes in Autistic Children

Effects of Acute Administration of Naltrexone on Cardiovascular Function, Body Temperature, Body Weight and Serum Concentrations of Liver Enzymes in Autistic Children

The opioid peptides. A role in hypertension?

Binding of <sup>3</sup>H-D-Pen<sup>2</sup>-D-Pen<sup>5</sup>-Enkephalin to Brain Regions and Spinal Cord Membranes of Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats

Contact Info

Product

Resources

About