The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Feb 1986
Altered pulmonary vascular smooth muscle responsiveness in monocrotaline-induced pulmonary hypertension.
Studies were conducted to determine whether experimental pulmonary hypertension is associated with alterations in pulmonary vascular smooth muscle responsiveness. Adult male rats were given a single s.c. injection of monocrotaline (105 mg/kg) or saline and were sacrificed 4, 7 or 14 days later. Segments of the main trunk and right extrapulmonary artery and an intrapulmonary artery were isolated for determination of vascular reactivity to contractile and relaxant agonists. ⋯ These results demonstrate that changes in pulmonary vascular smooth muscle responsiveness occur during evolution of pulmonary hypertension induced by monocrotaline. Enhanced contractility may contribute to inappropriate vasoconstriction early in the development of hypertensive pulmonary vascular disease but does not appear to be involved in sustained elevations in pulmonary artery pressure. Diminished relaxation observed after pulmonary hypertension was well established may contribute to the loss in efficacy of vasodilators in the long-term management of pulmonary hypertension.
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J. Pharmacol. Exp. Ther. · Jan 1986
Independent central and peripheral mediation of morphine-induced inhibition of gastrointestinal transit in rats.
The individual contributions of central (brain) and peripheral (enteric) sites in the mediation of the systemic actions of opioids are not well established. In this study, we made use of naltrexone methobromide, a quaternary analog of naltrexone, to separate the central and peripheral components of the slowing action of morphine on gastrointestinal transit in rats. It was established that i.c.v., but not s.c., administration of quaternary naltrexone antagonized morphine-induced analgesia in the radiant-heat tail-flick assay in rats. ⋯ Distinct and independent central and peripheral systems appear to mediate morphine-induced inhibition of gastrointestinal transit in rats. However, the receptors are probably of the same type. Peripherally selective antagonists such as quaternary naltrexone may be useful in reversing morphine-induced inhibition of gastrointestinal transit without affecting analgesia.
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J. Pharmacol. Exp. Ther. · Sep 1985
Morphine-induced mydriasis and inhibition of pupillary light reflex and fluctuations in the cat.
Morphine has species-characteristic effects on pupillary size The effects of morphine on pupillary size, fluctuations and the light reflex were tested with an infrared video pupillometer in the gallamine-paralyzed cat. Compared with saline or base-line responses, i.v. morphine (0.06-1.5 mg/kg) caused a dose-related decrease in the light reflex and fluctuations but increased pupil size. Naloxone (1-100 micrograms/kg i.v.), injected 1 h after morphine, reversed all pupillary effects. ⋯ It was concluded that morphine disrupts parasympathetic innervation of the iris through interactions with opiate receptors, some of which are in the brain. The morphine-induced changes on the light reflex and fluctuations in the cat are opposite those reported in the rat and rabbit. These results enlarge on the familiar species-dependent effects of opiates on pupillary size.
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J. Pharmacol. Exp. Ther. · Jun 1985
Comparative StudyAlpha-1 adrenergic control of the venous circulation in intact dogs.
To study alpha adrenergic control of the venous circulation, 17 dogs were lightly sedated and instrumented with thermodilution pulmonary flow and aortic catheters. Hemodynamics, cardiac output and central blood volume were measured at rest. Mean circulatory filling pressure, pressure gradient for venous return and resistance to venous return were calculated from pressures obtained during transient acetylcholine-induced circulatory arrest. ⋯ To eliminate reflex changes in vascular tone, eight dogs received ganglionic blockade with trimethaphan. After ganglionic blockade phenylephrine increased cardiac output, systemic vascular resistance, mean circulatory filling pressure, pressure gradient for venous return and central blood volume (P less than .025). Thus, in conscious dogs, phenylephrine reduces peripheral vascular capacitance and shifts blood from the venous circulation to the central and arterial vascular compartments.
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J. Pharmacol. Exp. Ther. · Jan 1985
Differential actions of intrathecal naloxone on blocking the tail-flick inhibition induced by intraventricular beta-endorphin and morphine in rats.
In the present study, it is proposed that the opioids applied to supraspinal brain sites produced their analgesic effects by the activation of different descending pain inhibitory systems. The blockade of the spinal endorphinergic system by intrathecal naloxone on the production of tail-flick inhibition induced by intraventricular beta-endorphin and morphine was then studied. Intraventricular injection of beta-endorphin and morphine produced an inhibition of the tail-flick response to the heat stimulus in rats. ⋯ On the other hand, intrathecal naloxone (12-120 micrograms) had only a very weak effect on the tail-flick inhibition induced by intraventricular morphine (40 micrograms). Intraventricular injection of naloxone at doses of 1.2 to 12 micrograms equally antagonized in a dose-dependent manner the tail-flick inhibition induced by intraventricular beta-endorphin and morphine. The results indicate that a spinal naloxone-sensitive endorphinergic system is involved in the production of beta-endorphin but not morphine-induced tail-flick inhibition, and suggest that intraventricular beta-endorphin and morphine elicit their pharmacological actions via the activation of different descending pain inhibitory systems; descending epsilon and mu systems for beta-endorphin and morphine, respectively, are proposed.