Phentolamine—an unexpected agonist in the rabbit

Angus, James A.; Lew, Michael J.

doi:10.1111/j.1476-5381.1984.tb10094.x

Cited by 17 publications

(9 citation statements)

References 8 publications

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“…* * P < 0.01 compared to baseline on day 1; + P < 0.05 compared to baseline on day 2 (d2); and ns, P > 0.05 (Student's paired t test). Lew, 1984). For our purposes, the direction of change is immaterial; the drug altered heart rate through an adrenergic effect but had no significant influence on RHDN.…”

Section: Discussionmentioning

confidence: 91%

“…Phentolamine caused a decrease in heart rate rather than the expected increase. This can be explained by the fact that in rabbits it is a presynaptic α 2 ‐receptor agonist as well as a non‐selective α 1 and α 2 inhibitor (Angus & Lew, 1984). For our purposes, the direction of change is immaterial; the drug altered heart rate through an adrenergic effect but had no significant influence on RHDN.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for a specific influence of the nitrergic pathway on the peripheral pulse waveform in rabbits

Nier¹,

Harrington²,

Carrier³

et al. 2008

Experimental Physiology

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The height of the dicrotic notch between the systolic and diastolic peaks of the peripheral pulse wave, expressed as a fraction of the overall amplitude of the wave, is sensitive to nitric oxide (NO) bioactivity. This phenomenon might form the basis of a simple, non-invasive method for determining endothelial function in vivo. We assessed whether the phenomenon is specific to the NO pathway or whether other vasoactive agents have similar effects. The relative height of the dicrotic notch (RHDN) was determined by photoplethysmography in the rabbit ear. It was dose-dependently decreased by acetylcholine, a stimulator of endothelial NO synthesis, and increased by N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. There was no effect on RHDN of the α-adrenergic blocker phentolamine or the β-adrenergic blocker propranolol. The cyclo-oxygenase inhibitor indomethacin dose-dependently decreased RHDN but this effect was blocked by L-NAME, suggesting it was mediated by cross-talk with the NO pathway. Changes in RHDN appeared to be independent of heart rate and of the delay between the systolic peak and the notch, but were associated with changes in the slope of the dicrotic limb. Both L-NAME and phentolamine produced multiple diastolic peaks, indicative of wave reflections in the vasculature. These data support the view that changes in RHDN are specific to the NO pathway and provide additional information about the mechanisms involved.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Evidence for a specific influence of the nitrergic pathway on the peripheral pulse waveform in rabbits

Nier¹,

Harrington²,

Carrier³

et al. 2008

Experimental Physiology

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“…The anomalous effects seen with phentolamine could perhaps be explained in terms of several experimental findings: phentolamine may increase circulating levels of endogeneous catecholamines and these raised levels of catecholamines could increase plasma cyclic AMP (Kunitade & Ui, 1978) and plasma glucagon (Miller & Horton, 1979). In any case phentolamine has been recently described as an unexpected agonist in the rabbit (Angus & Lew, 1984) making this drug unsuitable as an o-adrenoceptor antagonist in this species.…”

Section: Discussionmentioning

confidence: 99%

α‐Adrenoceptor involvement in catecholamine‐induced hyperglycaemia in conscious fasted rabbits

Moratinos

Olmedilla

Pablos

et al. 1986

British J Pharmacology

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1 In conscious fasted rabbits an intravenous infusion of phenylephrine (20 ptg kg-' min-) induced hyperglycaemia. The increase in blood glucose was accompanied by a modest increase in insulin secretion and a reduction of liver glycogen. Muscle glycogen and blood lactate levels were not altered by treatment with phenylephrine. 2 Prazosin, 1 mg kg-I s.c., partially attenuated phenylephrine-induced hyperglycaemia.3 Phenoxybenzamine infusion (16.6pgkg-'min-') for 15min suppressed the increase in blood glucose and the reduction in liver glycogen evoked by phenylephrine. This a-adrenoceptor blocker also clearly attenuated the blood glucose elevation observed on infusing adrenaline at 0.3 fig kg'-min -. 4 Blockade by phenoxybenzamine of phenylephrine-and adrenaline-induced hyperglycaemia was not accompanied by a significant increase in immunoreactive insulin plasma levels.5 Yohimbine infused at a rate of 20 g kg-lmin', also completely blocked phenylephrine-induced hyperglycaemia. This suppressor effect was accompanied by a marked rebound in insulin secretion. 6 It is concluded that in normal fasted rabbits stimulation of a-adrenoceptors induces hyperglycaemia. The increase in blood glucose depends mainly on liver glycogenolysis and inhibition of insulin secretion. Separate blockade of each component suffices to reduce a-adrenoceptor-mediated hyperglycaemia.

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“…This last result could be attributed to the agonist properties of phentolamine on sympathetic endings. 46 …”

Section: Direct Effects Of Ne On Br Dischargementioning

confidence: 99%

Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.

Munch¹,

Thorén²,

Brown³

1987

Circulation Research

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The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously with aortic pressure and diameter. At constant suprathreshold pressure, NE had two dose-dependent effects. Inhibition was produced at low concentrations (10(-10)-10(-7) M), whereas excitation was produced at high concentrations (10(-6)-10(-5) M). Inhibition was attributed to BR unloading since the response was consistent with the fall in diameter, was mimicked by angiotensin II (10(-10)-10(-6) M), and was prevented by pretreatment with the smooth muscle relaxant sodium nitroprusside (10(-6) M) or the selective alpha 1-adrenergic antagonist, prazosin (10(-6) M). Excitation was attributed to direct activation of the BR endings since this response was independent of changes in diameter, was not mimicked by angiotensin II, and was not prevented by sodium nitroprusside but was blocked by prazosin. These results indicate that NE has two modes of action, one mediated by contraction of local vascular smooth muscle and the other due to direct excitation of the nerve endings. It was also found that BR discharge at given diameters decreased more when pressure was lowered (smooth muscle passive) than when the aorta constricted (smooth muscle active). Furthermore, if diameter was held constant during smooth muscle contraction, discharge increased, as opposed to decreasing at constant pressure. These later results suggest that BR responses to vasoactive agents reflect not only changes in wall dimension but perhaps changes in wall tension and/or the coupling relation between BR and smooth muscle structures.

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Phentolamine—an unexpected agonist in the rabbit

Cited by 17 publications

References 8 publications

Evidence for a specific influence of the nitrergic pathway on the peripheral pulse waveform in rabbits

Evidence for a specific influence of the nitrergic pathway on the peripheral pulse waveform in rabbits

α‐Adrenoceptor involvement in catecholamine‐induced hyperglycaemia in conscious fasted rabbits

Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.

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