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PubMed2003

Phentolamine administration increases blood S100B protein levels in pediatric open-heart surgery patients.

AIM: Phentolamine administration during open-heart surgery shortens the cooling and rewarming phases of cardiopulmonary bypass (CPB) and hastens weaning from mechanical ventilation and extubation. Data on the effects of phentolamine on cerebral circulation and function in this setting are lacking. This study reports the cerebral effects of phentolamine using blood S100B protein levels and the middle cerebral artery pulsatility index (MCA PI). METHODS: Sixty pediatric patients undergoing congenital heart disease repair were randomly assigned to receive either phentolamine 0.2 mg kg(-1) i.v. (n = 30) or placebo (n = 30) before the cooling and rewarming phases of CPB. Samples for S100B measurement were collected at seven predetermined time-points before, during and after surgery. MCA PI values were recorded at the same times as sampling. RESULTS: S100B blood levels were higher in the phentolamine-treated group than in controls after rewarming (3.53 +/- 1.88 vs 1.58 +/- 0.53 microg l(-1); p < 0.001), remained persistently higher at the end of surgery (2.95 +/- 0.91 vs 0.79 +/- 0.21 microg l(-1); p < 0.001) and returned to normal ranges 12 h later than in the placebo group (p > 0.05). MCA PI values were also significantly higher at the end of surgery in the phentolamine-treated group (1.83 +/- 0.50 vs 1.22 +/- 0.34; p < 0.01). Cooling and rewarming times were shorter in the phentolamine-treated group (p < 0.01, for all). CONCLUSION: Despite improved peripheral vasodilatation and perfusion, phentolamine administration in pediatric open-heart surgery is correlated with increased cerebrovascular resistance and brain damage.

Adrenergic alpha-Antagonists↗
PubMed1989

Phentolamine and structurally related compounds selectively antagonize the vascular actions of the K+ channel opener, cromromakalim.

1. The effects of cromakalim, a novel vasodilator agent believed to open K+ channels, were studied in a range of large and small arteries in vitro. In dog isolated coronary artery, precontracted with U46619 (a thromboxane A2-mimetic), cromakalim caused concentration-dependent relaxation which could be inhibited by phentolamine (10-100 microM). 2. The ability of phentolamine to antagonize cromakalim was selective since it did not affect responses to a number of other vasodilators including isoprenaline, nitroprusside or nicorandil. 3. The effect of phentolamine was not related to its alpha-adrenoceptor blocking actions since other alpha-adrenoceptor antagonists (prazosin 10 microM, rauwolscine 10 microM and phenoxybenzamine 1 microM) failed to influence the action of cromakalim. 4. A number of compounds structurally related to phentolamine were also able to block the vaso-relaxant response to cromakalim in the dog isolated coronary artery. The rank order of potency was alinidine = phentolamine = ST91 greater than tramazoline = naphazoline. Clonidine and tolazoline were inactive. The most potent compounds (alinidine and phentolamine) were effective only at concentrations above 1 microM. 5. Electrophysiological studies, in which resting membrane potential and tension were measured simultaneously, were carried out on rat isolated femoral artery. Phentolamine (30 microM) antagonized both the vasorelaxation and hyperpolarization caused by cromakalim. 6. These results suggest that phentolamine and some structurally related compounds, may inhibit K+ channel opening, an action which would account for their ability to antagonize the actions of cromakalim. Such compounds may prove useful in determining the role of K+ channels in regulating vascular smooth muscle tone in vivo and in vitro.

Animals↗
PubMed1991

Block of ATP-regulated potassium channels by phentolamine and other alpha-adrenoceptor antagonists.

1. The patch clamp technique has been used to characterize the effects of phentolamine, an unselective blocker of alpha 1- and alpha 2-adrenoceptors, on the electrical activity of isolated RINm5F insulin-secreting cells and the gating of ATP-regulated potassium (K+ATP) channels. 2. Current-clamp experiments carried out by use of both conventional whole-cell recordings and nystatin-perforated cells, have demonstrated that phentolamine (5-20 microM) in the complete absence of alpha-adrenoceptor agonists, caused a sharp depolarization of the cell membrane from approximately -66 mV to -42 mV. This depolarization was associated with the generation of calcium action potential-like spikes. In the continued presence of phentolamine, diazoxide (100 microM) reversed these effects by causing a hyperpolarization of the cell, thereby preventing Ca2+ spikes. 3. Unitary current events from K+ATP channels were recorded from both outside-out membrane patches and saponin permeabilized or open-cells. When added to either the inside or the outside of the plasma membrane, phentolamine (0.1-100 microM) blocked openings from these channels. The effects of phentolamine were rapid, sustained and fully reversible. Phentolamine was apparently a more effective blocker of channels from the inside than the outside of the membrane. 4. The KI value, corresponding to 50% inhibition of channels was estimated to be approximately 0.7 microM when phentolamine was added to the inside of the membrane and the Hill coefficient approximately 1. 5. Yohimbine (1-10 microM) and the chemically 2-substituted imidazoline alpha-adrenoceptor antagonists, antazoline (25 microM) and tolazoline (25 microM) were also found to block K+ATP channels in isolated patches of membrane. 6. In conclusion the present study demonstrates that phentolamine and other imidazoline adrenoceptor antagonists have effects upon ATP-sensitive K+ channels that are not associated with stimulation of the adrenoceptor.

Adenosine Triphosphate↗
PubMed1988

The biochemical actions of phentolamine and papaverine on rat perfused skeletal muscle.

The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine-treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use.

Animals↗
PubMed1980

Effects of phentolamine on hepatic PO2 in endotoxemia.

The effect of phentolamine, an alpha-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Echerichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine-endotoxic rats. Arterial PO2 and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 +/- 2.5 vs. 77 +/- 5.6 mg%, mean +/- SE). Mean hepatic PO2 at 6 h in phentolamine-endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic PO2 was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia.

Animals↗
PubMed1985

Phentolamine and rat aortic smooth muscle responsiveness to potassium chloride, isoproterenol and norepinephrine.

Rat aortic smooth muscle responsiveness to potassium chloride and isoproterenol in the presence of the alpha-adrenergic blocker phentolamine was investigated. A A significant decrease in the response of the vascular smooth muscle of aorta to low concentrations of potassium chloride (KCl; 8-12 mM) in the presence of phentolamine was observed. However, no effect of phentolamine was seen at KCl concentrations greater than 16 mM. Isoproterenol-induced relaxation was significantly increased in aortic smooth muscle incubated with phentolamine. Phentolamine also attenuated the contraction induced by high concentrations of isoproterenol. No long-lasting effect of the alpha-adrenergic blocker was apparent since the response to norepinephrine was not altered following a 1-hour washout of phentolamine after the isoproterenol dose-response curve. The results of this study suggest that: (i) phentolamine has no long-lasting effects on rat aortic smooth muscle; (ii) since the rat thoracic aorta has a sparse adrenergic innervation, the decrease in responsiveness to KCl in the presence of phentolamine is most likely due to a nonspecific effect on the vascular smooth muscle as opposed to blocking the effects of norepinephrine released from adrenergic nerve terminals, and (iii) the increased relaxation response to isoproterenol may be due to a blockade of the alpha-receptors activated by isoproterenol.

Animals↗
PubMed1986

Differential effects of phentolamine on the responsiveness of aortic and femoral smooth muscle from normotensive and DOCA/NaCl hypertensive rats.

The in vitro responsiveness of rat aortic and femoral arterial smooth muscle from normotensive and deoxycorticosterone acetate (DOCA)/NaCl-induced hypertensive rats to potassium chloride (KCl) and isoproterenol (ISO) in the presence and absence of the alpha-adrenergic blocker phentolamine was investigated. Femoral but not aortic smooth muscle from the DOCA/NaCl rat exhibited an enhanced sensitivity to KCl stimulation when compared to controls. Phentolamine had no effect on femoral smooth muscle from control or DOCA/NaCl rats. However, a significant decrease in the sensitivity of aortic smooth muscle responsiveness to KCl in the presence of phentolamine was observed in both the control and hypertensive groups. Isoproterenol-induced relaxation of both aortic and femoral smooth muscle was significantly attenuated in the DOCA/NaCl rat when compared to controls. Incubation with phentolamine resulted in a significant increase in the relaxation response to ISO in aortic and femoral smooth muscle from controls. This increased responsiveness, however, was not observed in DOCA/NaCl rats. The contractile response to high doses of ISO was attenuated with phentolamine in all groups. A significant increase in the sensitivity to norepinephrine (NE) was observed in both aortic and femoral smooth muscle from the DOCA/NaCl rat when compared to controls. Whereas aortic and femoral smooth muscle from the DOCA/NaCl rat which had been exposed to phentolamine previously in the experiment exhibited a significant decrease in the sensitivity to NE following a one hour washout of the phentolamine, no long-lasting effect of phentolamine was apparent in vessels from controls. The results of this study confirm previous studies that the vascular smooth muscle responsiveness to NE is increased and ISO-induced relaxation is decreased in the DOCA/NaCl rat and demonstrate that these altered adrenergic responses are similarly manifested in the femoral smooth muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Local anesthetic action of phentolamine on insect mechanoreceptors.

1. The effect of phentolamine on the response properties of insect mechanoreceptors and on the conduction in their axons was examined using electrophysiological techniques. 2. Phentolamine blocked conduction of action potentials along axons, an effect which exhibited 3 characteristics typical of local anesthetics: the effect was frequency-dependent, reversible and varied for nerves with different diameters. 3. The concentration of phentolamine required to block axonal conduction (1-2 x 10(-3) M) was significantly higher than that required to abolish the response of receptors to mechanical stimulation (3-5 x 10(-4) M). 4. All mechanoreceptors that were examined in Locusta migratoria and Periplaneta americana were inactivated by phentolamine (Table 1). The type I receptors (chordotonal, campaniform and hair sensilla) were inactivated within 5-15 min following phentolamine application. The only type II receptor examined (forewing stretch-receptor) underwent a phase of repetitive discharge before being inactivated. 5. Tolazoline and metoclopramide inactivated, like phentolamine, mechanoreceptors at lower concentrations than necessary to block axonal conduction. However, yohimbine and chlorpromazine inactivated mechanoreceptors and blocked axonal conduction at similar concentrations. 6. These findings suggest that phentolamine affects sense-organ specific ionic processes that are more sensitive to the drug than the ionic processes along the axons.

Action Potentials↗
PubMed1990

Chemical deafferentation of the locust flight system by phentolamine.

1. Phentolamine was injected into the haemolymph of locusts, Locusta migratoria, and its effects on the flight system were analyzed using electrophysiological techniques. 2. Doses of 150 microliters at 10(-2) M phentolamine inactivated the wing stretch-receptors and tegulae without influencing the central nervous system (CNS). The lack of effect on the CNS was demonstrated by the absence of any effect on the flight motor pattern in animals that had been mechanically deafferented prior to the administration of phentolamine. From these observations we conclude that phentolamine can be used to chemically deafferent the flight system of the locust. Consistent with this conclusion is that the administration of phentolamine in intact animals changed the flight motor pattern so that it resembled the pattern occurring in mechanically deafferented animals. 3. The two main advantages of deafferenting the flight system by injecting phentolamine were a) intracellular recordings from central neurons could be easily maintained during the process of deafferentation, and b) the contribution of different groups of proprioceptors to the generation of the motor pattern could be assessed since not all proprioceptors were inactivated simultaneously. 4. By intracellularly recording from elevator motoneurons and administering phentolamine we confirmed a number of previous results related to the function of the wing stretch-receptors and the tegulae.

Animals↗
PubMed1980

Antagonism by chlorisondamine and propranolol, but not by atenolol, of the circadian phase-dependent phentolamine-induced changes in the cardiac noradrenaline turnover in the rat.

The effects of phentolamine alone or in combination with propranolol, atenolol and chlorisondamine were studied on the concentration and turnover of noradrenaline in the heart of light-dark (L:D = 12:12 h) synchronized rats. In order to detect possible circadian phase-dependent variations in the drug effects, the same experiments were performed in the light-period and dark-period, respectively. The parameters of the turnover were calculated from the exponential decline of i.v. injected 3H-(-)-noradrenaline. Phentolamine significantly decreased the noradrenaline concentration during L, but not during D. Reduction in 3H-noradrenaline accumulation by phentolamine was 42.3% during L and 22.2% during D. Phentolamine increased the turnover rate of cardiac noradrenaline more than 3-fold in either photoperiod. Chlorisondamine reversed all the effects of phentolamine studied. Propranolol, but not atenolol, antagonized the effects of phentolamine in a dose-dependent and stereospecific way, being more effective when applied during D. Thus, the chronopharmacological studies in unrestrained rats show a circadian phase-dependency of the effects of adrenoceptor blocking drugs. It is concluded that a central site of action is responsible for the antagonism by propranolol of the phentolamine-induced increase in the turnover of the cardiac noradrenaline in vivo.

Animals↗
PubMed1978

Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.

Action Potentials↗
PubMed1998

No evidence for PKC activation in stimulation of insulin secretion by phentolamine.

The possible role of protein kinase C (PKC) activation in the course of insulin secretion induced by the imidazoline phentolamine was investigated by measuring the insulin secretion of perifused mouse islets and of insulin-secreting HIT cells and by measuring the PKC activity of HIT cells. When normal mouse islets were perifused with the imidazoline phentolamine (32 microM) or the sulfonylurea glibenclamide (1 microM), neither phentolamine nor glibenclamide could produce a stimulation of secretion which was stronger than that elicited by a strong depolarization. Under the same conditions, tetradecanoylphorbolacetate (TPA, 50 nM), a known activator of PKC activity in pancreatic islets, markedly enhanced the secretion induced by K+ depolarization. Phentolamine also stimulated insulin secretion of superfused HIT cells. When PKC activity in HIT cells was down-regulated to 15% of the initial value by overnight exposure to TPA (50 nM), the stimulatory effect of TPA on secretion was virtually abolished, while phentolamine was still able to elicit a monophasic secretion. TPA (50 nM) induced the typical redistribution of PKC activity in HIT cells: within 2 min, the share of membrane-bound PKC activity rose from 26% to 87% of the total PKC activity, which remained unchanged. In contrast, phentolamine (32 microM) had no effect on PKC distribution, did not down-regulate PKC and had no effect on PKC activity once it was down-regulated by TPA. Thus, the recent suggestion that the insulinotropic effect of imidazolines involves an activation of PKC could not be verified for phentolamine.

Animals↗
PubMed1979

Evaluation of phentolamine as a provocative test for idiopathic hypertrophic subaortic stenosis.

Intravenous injection of phentolamine potentially offers a better provocative test for aortic left ventricular outflow tract obstruction than do Valsalva's maneuver, inhalation of isoproterenol, or of amyl nitrite. In hemodynamic studies, phentolamine enhanced myocardial contractility, and decreased afterload with only induction of slight tachycardia. Phentolamine (5 mg.) was administered intravenously to five patients who had idiopathic hypertrophic subaortic stenosis, and 35 patients who had valvular dysfunctions, after which echocardiographic and phonocardiographic recordings were performed. Recordings were of high quality despite changing hemodynamics. Systolic pressures fell an average of 20 mm. Hg; no pressure fell below 90 mm. Hg; there was no notable increase in heart rate. In the five patients with typical idiopathic hypertrophic subaortic stenosis, the amyl nitrite increased the obstructive index from 39.6 +/- 12 to 51 +/- 18.9 (P less than 0.05); whereas, phentolamine increased the obstructive index to 69.8 +/- 25.6 (P less than 0.015). After a 2 week course of oral administration of 80 mg. of propranolol daily, and then either inhalation of amyl nitrite or injection of phentolamine, there was no change from the mean resting obstructive index. Phentolamine appears to be a safe, simple and specific diagnostic agent, and more potent than amyl nitrite in eliciting dynamic obstruction in IHSS; phentolamine and amyl nitrite do not affect the obstructive index in patients with beta blockade.

Amyl Nitrite↗
PubMed1977

Central cardiovascular effects of phentolamine in chloralose-anesthetized cats.

Phentolamine (50, 100 and 200 microng/min for 30 min) perfused through the cerebroven system of chloralose-anesthetized cats produced dose-related reductions in tricular blood pressure. Evidence is presented which suggests that this hypotensive activity was due to an interaction at central nervous system sites and was not attributable to escape of the compound from the brain. Centrally administered phentolamine was more effective in lowering blood pressure than the i.v. infusion of phentolamine at a dose (25 microng/kg/min for 30 min) which markedly antagonized peripheral alpha-adrenoceptors. In addition, central phentolamine induced bradycardia in contrast to the tachycardia which accompanied i.v. administration. By limiting the perfusion of phentolamine to selected portions of the cerebrospinal fluid spaces a major site of action responsible for the hypotensive activity was located outside the ventricles in an area accessible from the subarachnoid spaces. A second, less important site, anterior to the midbrain adjacent to the ventricular system apparently contributed to the hypotension. Phentolamine, introduced centrally, also impaired reflexogenic bradycardia elicited by pressor doses of norepinephrine. Both the sympathetic withdrawal and the vagal activation which account for this reflex seemed to be antagonized by phentolamine.

Anesthesia↗
PubMed1992

Smooth muscle relaxation and inhibition of responses to pinacidil and cromakalim induced by phentolamine in guinea-pig isolated trachea.

A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation when the tone was induced by histamine, carbachol, 30 mM K+ or 124 mM K+. Relaxant EC50 values ranged from 8 to 50 microM with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F2 alpha (PGF2 alpha) or leukotriene C4 (LTC4). At a concentration of 100 microM the alpha 2-adrenoceptor blocker, yohimbine, produced minor inhibition of spasmogen-induced tone, whereas the alpha 1-adrenoceptor blocker prazosin (up to 10 microM) had no inhibitory effects in the trachealis. Propranolol (1 microM), prazosin (1 microM), yohimbine (100 microM), tetrodotoxin (3 microM), glibenclamide (10 microM), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100 microM), dipyridamole (3 microM) or methylene blue (100 microM) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF2 alpha or LTC4, phentolamine (1, 10 and 100 microM) antagonized the relaxant action of the K+ channel openers, pinacidil and cromakalim. The concentration-relaxation curves for pinacidil were shifted 30-fold to the right without change in the maximal effects, whereas the maximal cromakalim-induced relaxant responses were markedly suppressed by phentolamine.

Animals↗
PubMed1989

Antagonism of bromobenzene-induced hepatotoxicity by the alpha-adrenoreceptor blocking agents phentolamine and idazoxan: role of hypothermia.

A recent study from our laboratory revealed that cotreating mice with the alpha-adrenoreceptor antagonists phentolamine and idazoxan markedly diminished bromobenzene-induced hepatotoxicity. Subsequent studies also revealed that such cotreatment does not alter the pharmacokinetic disposition of bromobenzene in mice nor its bioactivation to reactive metabolites. In the present study, the possible role of hypothermia in the phentolamine antagonism of bromobenzene-induced hepatotoxicity was investigated. Bromobenzene alone caused a significant, dose-related hypothermia. The high dosage regimen (10 mg/kg per dose) of phentolamine or idazoxan that had been found to be hepatoprotective in earlier studies potentiated this hypothermia and more than doubled the net decrease in core body temperature experienced by the animals. Placing mice receiving bromobenzene in an environment with an ambient temperature of 10 degrees C likewise increased the hypothermia experienced by animals receiving bromobenzene. The magnitude of the net change in core body temperature elicited by exposure to cold was similar to but slightly less than the net change produced by cotreatment with either alpha-adrenoreceptor antagonist and the magnitude of the hepatoprotection this procedure provided against bromobenzene hepatotoxicity was equivalent to that observed with phentolamine cotreatment. In contrast, a lower dosage regimen of either adrenoreceptor antagonist (2.5 mg/kg per dose) resulted in no additional hypothermia yet still produced a near maximal antagonism of bromobenzene-induced hepatotoxicity. Further, increasing the ambient temperature to 30 degrees C completely reversed the phentolamine-induced (10 mg/kg per dose) increase in hypothermia, but did not affect phentolamine's antagonism of the bromobenzene-induced changes in hepatic glutathione levels, serum alanine aminotransferase activity, or 24-hr mortality. Therefore, we conclude that while the hepatoprotective intervention of phentolamine can be mimicked by an exposure to cold that results in hypothermia, it is clear that alpha-adrenergic antagonists diminish the hepatotoxicity induced by bromobenzene by a mechanism that is independent of hypothermia.

Adrenergic alpha-Antagonists↗
PubMed1998

Phentolamine effect on the spontaneous electrical activity of active loci in a myofascial trigger spot of rabbit skeletal muscle.

OBJECTIVE: To investigate the effect of phentolamine, a sympathetic blocking agent, on the spontaneous electrical activity (SEA) recorded from a locus of a myofascial trigger spot (MTrS), equivalent to a human trigger point, in rabbit skeletal muscle. DESIGN: Randomized control trial. SETTING: A university medical laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine adult New Zealand rabbits. INTERVENTION: In the experimental group phentolamine mesylate (1mg/kg) was injected into the external iliac artery, followed by flushing with normal saline. The control group was treated with normal saline instead of phentolamine using the same procedure. MAIN OUTCOME MEASURES: SEA was recorded from multiple active loci of MTrSs in the biceps femoris muscle: initially SEA in the same locus was recorded before and immediately after phentolamine (or normal saline) injection; then SEA was recorded from 25 different active loci. The mean of the average integrated signal (AIS) of SEA was analyzed, comparing the effects of phentolamine and normal saline on SEA. RESULTS: In the same active locus, the AIS of SEA showed statistically a linear decay with time after phentolamine injection, with a correlation coefficient of .56 at p < .05. However, no statistical relationship could be derived for the control group data with time by using regression analysis, probably because of large variations among the rabbits and movement artifacts during the experiment. In 25 different loci in the phentolamine group, the mean of the AIS of SEA (7.92 microV) was significantly lower than that of the control group (9.89 microV) at p < .05. CONCLUSIONS: The results support the hypothesis that the autonomic nervous system is involved in the pathogenesis of myofascial trigger points. The application of the AIS as an evaluation index seems to be feasible in the quantitative measurement of SEA.

Adrenergic alpha-Antagonists↗
PubMed1988

Antagonism of bromobenzene-induced hepatotoxicity by phentolamine: evidence for a metabolism-independent intervention.

A previous study has revealed that phentolamine markedly antagonizes the bromobenzene-induced hepatotoxicity and lethality in B6C3F1 mice. One potential mechanism by which phentolamine may diminish the bromobenzene-induced hepatotoxicity is by a direct or indirect interference with the metabolism of bromobenzene to toxic metabolites. In the present study, phentolamine cotreatment failed to alter the elimination of bromobenzene from serum or the distribution of bromobenzene to liver. This suggests that phentolamine cotreatment does not indirectly interfere with bromobenzene bioactivation secondary to changes in bromobenzene absorption, distribution, or elimination. Further, a phentolamine concentration 10- to 20-fold greater than those measured in vivo failed to alter the in vitro metabolism of bromobenzene to its ortho- and para-phenolic metabolites. It is believed that para-bromophenol represents the rearrangement product of the hepatotoxic 3,4-epoxide and that ortho-bromophenol is a product of the nonhepatotoxic 2,3-epoxide pathway. Thus, it appears that phentolamine does not antagonize bromobenzene-induced hepatotoxicity by inhibiting the formation of hepatotoxic intermediates, nor by enhancing metabolism via the nonhepatotoxic pathway. On the basis of these studies, we conclude that phentolamine antagonism of bromobenzene-induced hepatotoxicity occurs through a mechanism independent of bromobenzene bioactivation.

Adrenergic alpha-Antagonists↗