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PubMedDate not supplied

Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel.

To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (approximately 50%) in HCC strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin (1 microM) (54.6+/-4.6 vs 48.9+/-6.4%) or (atropine (10 microM) (52.7+/-6.5 vs 58.6+/-5.6%). However, this relaxation was significantly attenuated by L-NAME (100 microM) (59.7+/-5.8 vs 27.8+/-7.1%; P<0.05; n = 8) and ODQ (100 microM) (62.7+/-5.1 vs 26.8+/-3.9%; P<0.05; n = 8). Charybdotoxin and apamin (K(Ca)-channel blockers) did not affect the phentolamine relaxations (54.6+/-4.6 vs 59.3+/-5.2%). Glibenclamide (100 microM), an inhibitor of K(ATP)-channel, caused a significant inhibition (56.7+/-6.3 vs 11.3+/-2.3%; P<0.05; n = 8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6+/-5.6 vs 5.7+/-1.4%; P<0.05; n = 8). The results suggest that phentolamine relaxes HCC by a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase activity and activation of K(ATP)-channel.

Adrenergic alpha-Antagonists↗
PubMed2001

Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanism.

The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of the rabbit corpus cavernosum elicited frequency-related relaxation that was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of rabbit corpus cavernosum, suggesting that neuronal release of NO mediates relaxation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxation of the rabbit corpus cavernosum. Prazosin (30 microM) and yohimbine (30 microM) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit corpus cavernosum independent of alpha-adrenergic receptor blockade. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated electrical field stimulation produced relaxations to phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by activating NO synthase. The data suggest that phentolamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of alpha-adrenergic receptor blockade.

Adrenergic alpha-Antagonists↗
PubMed2001

Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning.

BACKGROUND: Phenylpropanolamine produces dose-related, life-threatening cardiovascular, and central nervous toxicity from alpha-adrenergic overstimulation. Although some recommend the alpha-adrenergic antagonist, phentolamine, as treatment for such toxicity, its therapeutic efficacy has not been previously studied. We sought to determine if pretreatment with phentolamine could reduce acute myocardial injury and mortality in rats administered an overdose of phenylpropanolamine. METHODS: In the mortality arm of the study, 28 unanesthetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equal volume of normal saline diluent (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury arm of the study, 20 unanesthetized rats (10 per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or normal saline (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours after phenylpropanolamine administration, all surviving animals were sacrificed and transverse sections of their hearts were graded histologically for injury by a blinded cardiac pathologist. RESULTS: Twelve rats died within 6 hours of phenylpropanolamine administration. Mortality was significantly lower in the phentolamine-pretreated rats (2/14; 14%) as compared to the control group (10/14; 71%; p = 0.006). The degree of myocardial injury was significantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012). CONCLUSION: In this rat model, phentolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.

Adrenergic alpha-Agonists↗
PubMed1994

Phentolamine blocks ATP sensitive potassium channels in cardiac ventricular cells.

OBJECTIVE: The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of this study was to examine the effect of phentolamine on the ATP sensitive potassium channel (KATP), because this channel seems to be involved in action potential shortening during ischaemia. METHODS: Single channel experiments were performed on inside-out and outside-out patches of isolated rabbit ventricular cells at room temperature. Cells were isolated with conventional isolation techniques. Pipette and bath solution contained (in mmol.litre-1): K-gluconate 140, KCl 10, and HEPES-KOH 10 (pH 7.4). RESULTS: Excision of the patch always resulted in KATP channel activity [single channel conductance 60(SD 2.8) pS n = 4], which could be completely blocked by 5 mM ATP. In 22 of 26 patches the addition of 5 microM phentolamine to the intracellular side of the membrane reduced KATP channel activity. In 17 of these patches the effect was reversible. In four patches no effect was observed. Open probability decreased by 94% (n = 12). Addition of 50 microM phentolamine resulted in the disappearance of channel activity in six of eight patches which was reversible in four patches. In outside-out patches 5 microM phentolamine was only effective in 50% of the patches, reducing open probability by 98 to 100%. CONCLUSIONS: Phentolamine blocks ATP sensitive potassium channels in rabbit ventricular cells independently of the alpha adrenoceptor. This blocking effect probably occurs at the intracellular side of the membrane. The antiarrhythmic effect of phentolamine may at least partially be explained by blockade of KATP channels and may thus partly be independent of its effects on the alpha adrenoceptor.

Action Potentials↗
PubMed1983

Phentolamine in low cardiac output states: an assessment with ECG-gated cardiac scintigraphy.

We examined the effect of parenteral phentolamine in 11 critically ill patients with a low cardiac output state and a high systemic resistance. Because vasodilators often affect left ventricular end-diastolic pressure-volume relationships (compliance) in acute cardiac disease, changes in the pulmonary capillary wedge pressure (WP) may conceivably not reflect the true effect of vasodilators on left ventricular preload. Hence, we measured left ventricular ejection fraction (LVEF) with ECG-gated cardiac scintigraphy and stroke volume by thermodilution before and during phentolamine infusion. We then calculated left ventricular end-diastolic volume index (LVEDVI). Phentolamine infusion was associated with an increase in the mean cardiac index (CI) (1.96 +/- .53 [mean +/- SD] to 2.45 +/- .69 L/min X m2; p less than .0025) whereas the mean WP fell (19.5 +/- 7.5 to 13.5 +/- 7.3 mm Hg; p less than .05). There was no simultaneous change in the mean LVEDVI (100 +/- 48 to 110 +/- 40 ml/m2; p = NS), implying that one of the effects of phentolamine infusion was to improve left ventricular diastolic compliance. Multiple regression analysis suggested that the major effect of phentolamine on stroke volume was mediated by concomitant changes in the LVEDVI (r2 = .64). Therefore, benefit from phentolamine in low cardiac output states is multifactorial and phentolamine likely improves left ventricular compliance in some patients.

Aged↗
PubMed1985

Effect of phentolamine in controlling temperature and acidosis associated with cardiopulmonary bypass.

This study assessed the effects of phentolamine on rewarming patterns and metabolic acidosis in 37 patients subjected to hypothermia during cardiopulmonary bypass for the performance of aortocoronary bypass grafting. An additional 16 patients undergoing the same surgery received no phentolamine and served as a control group. In all patients, sodium bicarbonate (44.6 mEq) was administered only when the negative base excess was 3.0 mEq/L or greater. Sixty-eight percent of the patients receiving phentolamine and 56% of the control patients exhibited a uniform rewarming pattern in which the rectal, hand, and foot temperatures increased in parallel. In 32% of the patients receiving phentolamine and in 44% of the control patients, rectal and hand temperatures increased more than foot temperature during rewarming. Analysis of base excess values in the subgroups of patients with similar rewarming patterns indicated that base deficits were significantly decreased in patients receiving phentolamine. Phentolamine administration was also associated with significantly lower blood lactate levels and sodium bicarbonate requirements, as well as improvements in overall appearance and mental status. These data suggest that the routine use of phentolamine in patients undergoing cardiopulmonary bypass may be associated with more uniform body cooling and rewarming and improved tissue perfusion.

Acidosis↗
PubMedDate not supplied

Electrophysiologic and antiarrhythmic effects of phentolamine in experimental coronary artery occlusion and reperfusion in the dog.

We studied the electrophysiologic and antiarrhythmic effects of phentolamine on ventricular arrhythmias seen after acute coronary artery occlusion and reperfusion in the anesthetized dog. One group of animals underwent proximal left circumflex artery occlusion for 1 hr followed by 4 hr of reperfusion. One-half received phentolamine, 0.25 mg/kg bolus, 30 min before occlusion, followed by continuous intravenous infusion of 0.15 mg/kg/min throughout the experiment, while the other half received saline and served as controls. Phentolamine reduced the number of premature ventricular contractions (PVCs) during the reperfusion period but had no effect on postocclusion arrhythmias. Another group of dogs underwent ligation of two consecutive left anterior descending diagonal branches for 1 hr followed by reperfusion. Effective refractory periods and ventricular activation times were measured before occlusion, every 10 min during occlusion, and every 10 min during reperfusion in both normal and ischemic zones. In this model, phentolamine reduced both the number of PVCs and the complexity of ventricular ectopy seen in the first 10 min after reperfusion. Compared to control, phentolamine decreased the shortening of ischemic zone refractory period seen after occlusion and prevented the overshoot seen after reperfusion. Phentolamine had no effect on ventricular activation times or mean blood pressure. Phentolamine is effective in preventing reperfusion ventricular arrhythmias and may act by decreasing the dispersion of refractoriness between normal and ischemic zones during coronary occlusion and reperfusion and by preventing the rapid increase in refractory period after reperfusion.

Animals↗
PubMedDate not supplied

Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade.

We tested whether the alpha 1- and alpha 2-blocking agent phentolamine can be used to assess the contribution of alpha-adrenergic constriction in circulatory control. In 15 conscious dogs at rest, phentolamine (2 mg/kg i.v.) caused hypotension (-17 mm Hg mean arterial pressure), vasodilation (-29% total peripheral resistance), tachycardia, and an increase in cardiac output, oxygen consumption, and plasma catecholamines. Following beta-adrenoceptor blockade (2 mg/kg i.v. nadolol), phentolamine still produced hypotension and increased plasma catecholamine levels, but neither vasodilation nor augmented oxygen consumption. During beta-blockade, phentolamine caused a 28-fold decrease in the vasoconstrictor response to norepinephrine infusions. An equihypotensive dosage of the alpha 1-adrenoceptor blocking agent prazosin (1.2 mg/kg i.v.) did not elevate heart rate, cardiac output, plasma catecholamines, or oxygen consumption. The prazosin-induced vasodilation was not attenuated by prior beta-blockade, in contrast to the phentolamine-induced vasodilation. It is concluded that phentolamine increased catecholamine release by presynaptic alpha 2-blockade, thereby suppressing the autoinhibition of transmitter release. This excess of catecholamines causes a rise of oxygen consumption and vasodilation by beta-adrenergic stimulation. Under beta-blockade, this excess competitively counteracts the postsynaptic vascular alpha-blockade. The combination of pre- and postsynaptic effects invalidates the use of phentolamine in the assessment of alpha-adrenoceptor-mediated vasoconstrictor tone.

Animals↗
PubMed1980

Comparison of mianserin with desipramine, maprotiline and phentolamine on cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and noradrenaline reuptake in pithed normotensive rats.

1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic alpha-adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.2 Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.3 Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.4 All four compounds abolished the clonidine-induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic alpha-adrenoceptors.5 In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose-response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.6 In pithed, reserpine-treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose-response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).7 These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and also inhibits the neuronal reuptake of noradrenaline.

Animals↗
PubMed1983

A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart.

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments from the atrial and right ventricular free walls of rat hearts during superfusion and electrical stimulation in vitro at 37 degrees C. Availability of the fast sodium channels for current flow was inferred from the maximum rate of rise of membrane potential during phase 0 of the action potential. Phentolamine mesylate (2 to 20 microM) caused a concentration-dependent block of the fast sodium channel. This was reflected in prolongation of the refractory period and slowing of recovery of excitability following the action potential, without significant change in action potential duration or resting membrane potential. Increase in the concentration of KCl in the superfusate from 5 to 10 mM depolarized the muscle and potentiated the blocking action of phentolamine. Both the depolarizing and the phentolamine-potentiating actions of KCl were counteracted by simultaneous elevation of the concentration of CaCl2 in the superfusate from 2 to 10 mM. The blocking action of phentolamine was enhanced by increasing the frequency of electrical stimulation in the range 0.01 to 10 Hz. In respect of the properties listed above, lignocaine hydrochloride was similar to phentolamine but was different from quinidine sulphate in that the effects of the latter drug were not potentiated by KCl. Two other alpha-adrenoceptor antagonists, prazosin and yohimbine, both displayed actions similar to those shown by phentolamine. Tolazoline was only weakly active and dihydroergotamine (60 microM) was inactive. Dibenamine and phenoxybenzamine, unlike the previously named drugs, caused an irreversible block of the fast sodium channel. These blocking actions of alpha-adrenoceptor antagonists were not prevented by simultaneous exposure to the alpha-adrenoceptor agonist phenylephrine (1 mm). 8 Muscle from both reserpine pretreated and non-pretreated rats responded indistinguishably to phentolamine.

Action Potentials↗
PubMed1989

Cromakalim-induced relaxation of guinea-pig isolated trachealis: antagonism by glibenclamide and by phentolamine.

1. Tested against the spontaneous tone of guinea-pig isolated trachealis, cromakalim (0.1-100 microM), isoprenaline (1 nM-1 microM) and theophylline (1 microM-1 mM) each produced concentration-dependent relaxation. 2. Glibenclamide (0.1-10 microM) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast, glibenclamide (0.1 and 1 microM) caused a concentration-dependent rightward shift of the log concentration-effect curve of cromakalim. Glibenclamide (10 microM) reduced the slope of the log concentration-effect curve of cromakalim and moved the foot of the curve back towards the control position. 3. Phentolamine (1, 10 and 100 microm) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast phentolamine caused concentration-dependent depression of the log concentration-effect curve of cromakalim. 4. Neither prazosin (1 microM) nor yohimbine (10 microM) modified the spontaneous tone of the trachea. Prazosin and yohimbine each failed to antagonise the effects of cromakalim, isoprenaline and theophylline. 5. Intracellular electrophysiological recording showed that glibenclamide (1 microM) and phentolamine (100 microM) caused minor change in the resting membrane potential of trachealis cells. Slow wave activity was slightly depressed by these agents. In contrast tetraethylammonium (TEA; 8 mM) caused marked depolarisation, and promoted the conversion of slow waves into regenerative action potentials. These electrical changes were accompanied by tonic tension development. 6. Phentolamine (100 microM) and glibenclamide (1 microM) reduced and reversed both the relaxation and the hyperpolarisation induced by cromakalim (10 microM). 7. It is concluded that glibenclamide and phentolamine each provide selective antagonism of the relaxant action of cromakalim in guinea-pig trachealis. These agents also inhibit the plasmalemmal hyperpolarisation induced by cromakalim. The effect of phentolamine is unrelated to the blockade of alpha 1- or alpha 2-adrenoceptors. If either glibenclamide or phentolamine act to block the K+ channels opened by cromakalim, then such channels are not identical to those which endow the trachealis plasmalemma with its powerful rectifying behaviour.

Animals↗
PubMed1993

Attenuation by phentolamine of hypoxia and levcromakalim-induced abbreviation of the cardiac action potential.

1. The effects of phentolamine (5-30 microM) and glibenclamide (10 microM) on action potential characteristics were examined in guinea-pig papillary muscle exposed to either hypoxia or levcromakalim (20 microM). 2. The hypoxia-induced abbreviation of action potential duration (APD) and effective refractory period (ERP) were attenuated but not abolished by glibenclamide (10 microM). Hypoxia reduced APD by 24 +/- 2 vs 65 +/- 4% in glibenclamide- and vehicle-treated tissue, respectively. 3. Phentolamine (10-30 microM) was less effective than glibenclamide in attenuating the hypoxic shortening of APD since APD was reduced by 38 +/- 10, 51 +/- 6% vs 65 +/- 4% in 10 and 30 microM phentolamine and vehicle-treated muscle, respectively. 4. Phentolamine, at concentrations of 10 and 30 microM, also reduced the upstroke velocity of the action potential and at 5 microM it increased the APD from 193 +/- 9 to 221 +/- 12 ms. 5. Glibenclamide completely abolished and phentolamine (30 microM) significantly attenuated levcromakalim-induced changes in duration and ERP. Levcromakalim reduced APD by 71 +/- 2 and 55 +/- 2% in control and phentolamine pretreated muscle, respectively. 6. It is concluded that phentolamine may block KATP channels at concentrations that also block sodium channels.

Action Potentials↗
PubMed1985

Effects of alpha-adrenoceptor blockade by phentolamine on basal and stimulated insulin secretion in the mouse.

The sympathetic nervous system is known to innervate the pancreatic islets and to have the capability to influence islet hormone release. The effects are, however, complex since the islet nerves contain catecholaminergic as well as peptidergic fibres, and the catecholamines stimulate alpha- as well as beta-adrenoceptors. The present study was undertaken to establish the possible influence of the alpha-adrenoceptors on basal and stimulated insulin secretion under in vivo conditions. The alpha-adrenoceptor blocker phentolamine was injected at various dose levels i.p. to mice and a dose-dependent increase in plasma concentrations of insulin was seen. The maximal plasma insulin levels were observed 10 min after injection and were accompanied by decreased plasma glucose concentrations. Additionally, plasma glucose levels fell in response to phentolamine by an apparent insulin-independent manner, since at the low dose of 2.6 mumol kg-1, plasma glucose levels did decrease without any apparent increase in plasma insulin levels. After injection of a low dose of phentolamine 10 min prior to a rapid i.v. injection of one of four different insulin secretagogues, the following effects on insulin release were observed. Glucose (+55%) and the cholinergic agonist carbachol (+140%) displayed a potentiated insulin secretory response after phentolamine pretreatment, whereas the beta 2-adrenoceptor agonist terbutaline (-45%) had a blunted, though not abolished, insulin response. The absolute insulin secretory response to CCK-8 was unaffected by phentolamine despite the fact that plasma glucose levels were lowered by phentolamine. In conclusion, phentolamine enhanced insulin secretion and depressed plasma glucose levels in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1975

Alpha-receptor stimulation by endogenous and exogenous norepinephrine and blockade by phentolamine in pial arteries of cats.

The question regarding the existence of an alpha-adrenergic component of pial arterial tone was investigated using a microapplication technique combined with the measurement of vascular diameter. Concentration-response curves for the alpha-receptor blocker, phentolamine, revealed no vascular reaction for a concentration range from 2.5 x 10(-11) to 2.5 x 10(-7) M. At higher concentrations (up to 1.3 x 10(-3) M) concentration-dependent dilations were observed. Constrictions of pial arteries induced by perivascular injection of 2.5 x 10(-6) M norepinephrine could be reduced by 38% and 73% when phentolamine was applied simultaneously in concentrations of 2.5 x 10(-7) and 2.5 x 10(-6) M, respectively, whereas constrictions due to 2.5 x 10(-4) M norepinephrine were not reduced by 2.5 x 10(-6) M phentolamine, indicating a competitive antagonism between norepinephrine and phentolamine for pial arteries. Stimulation of the cervical sympathetic chain (90 seconds, 10 v, 1.4 msec, 20 Hz) induced constrictions of pial arteries (mean 12%) which could be reduced by two-thirds during the simultaneous application of 2.5 x 10(-7) M phentolamine. Since the constriction induced by norepinephrine applied exogenously or released endogenously could be reduced by a concentration of phentolamine which had no vascular effect per se, we conclude that the resting tone of the pial arteries is not influenced by an alpha-adrenergic component under our experimental conditions. The dilations induced by high concentrations of phentolamine are believed to be nonspecific.

Animals↗
PubMed2004

Phentolamine re-dosing during penile dynamic colour Doppler ultrasound: a practical method to abolish a false diagnosis of venous leakage in patients with erectile dysfunction.

Increased sympathetic tone may cause an equivocal response to a prostaglandin E1 (PGE1) penile Doppler ultrasound (US) examination interpreted as a venous leak. We evaluated the US parameters and erectile response to the addition of phentolamine to a PGE1 penile Doppler US examination to ascertain whether addition of phentolamine would abolish a suboptimal response. 32 patients (median age 29 years, range 17-70 years) with either a previous Doppler US pattern of venous leakage or a clinical suspicion of venogenic impotence, underwent Doppler US after a total dose of 20 microg of PGE1. Peak systolic velocity (PSV), end diastolic velocity (EDV) and grade of erection were documented. If erectile response was suboptimal irrespective of the EDV measurement, 2 mg-intracavernosal phentolamine was administered and measurements repeated. Six patients had a normal erectile response, the remaining 26 received phentolamine. A significant increase in PSV between baseline and 20 microg PGE1 (p<0.001) was observed in all cases. Following phentolamine there was a significant increase in grade of erection (p=0.0001) and a significant reduction in the EDV (p=0.0001). A reduction of the EDV to below 0.0 cm s(-1) was observed in 16 patients. Four patients with EDV <5.0 cm s(-1) but >0.0 cm s(-1) had improved erectile response following phentolamine while six showed persistent EDV elevation >5 cm s(-1). No priapism was documented. It is essential to ensure cavernosal relaxation using phentolamine before a Doppler US diagnosis of venous leak is made. This two-stage assessment will allow this to be done efficiently and with a low risk of priapism.

Adolescent↗
PubMed1979

Oral therapy with phentolamine in chronic congestive heart failure.

Therapy with phentolamine can improve the condition of patients with congestive heart failure due to the inotropic effect of this drug, as well as its vasodilating action. The use of oral therapy with phentolamine has not been adequately investigated in patients with chronic heart failure. Therefore, nine patients with chronic heart failure due to underlying valvular disease received 50 mg of phentolamine four times a day for two weeks. Echocardiograms and measurements of systolic time intervals were obtained prior to administration of phentolamine and two weeks after the introduction of therapy with the drug. As a result of therapy with phentolamine, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased, while the left atrial dimension decreased. Therapy with phentolamine produced a significant decrease in the preejection period index, as well as the ratio of the preejection period over the left ventricular ejection time. Thus, oral therapy with phentolamine improves left ventricular function in patients with chronic heart failure.

Administration, Oral↗
PubMed1974

Effects of phentolamine on the SA node of the dog heart in situ.

Direct perfusion of the sinus node artery at constant pressure of 100 mmHg was arranged in 6 canine hearts in situ. The injection of phentolamine into the sinus node artery usually induced dose-dependent positive chronotropic effect. However, at a larger dose of 300 mug, phentolamine frequently induced a biphasic chronotropic response, i.e., sinus deceleration followed by sinus acceleration. Phentolamine at a large dose of 1 mg usually induced a negative chronotropic effect. The threshold dose for inducing sinus acceleration was about 1 to 10 mug. The positive chronotropic response to phentolamine was blocked either by propranolol or by tetrodoxin. That to norepinephrine was blocked by propranolol but not suppressed by tetrodotoxin. These results suggest that the phentolamine-induced sinus acceleration is due to catecholamine which is released by excitation of local adrenergic fibers. The sinus deceleration to higher doses of phentolamine was not blocked either by atropine or by tetrodotoxin. It suggests that phentolamine has a direct depressive effect on the SA node at extremely high dose levels.

Animals↗
PubMed1982

The direct inhibitory action of phentolamine on the contraction of rabbit basilar artery.

The effects of phentolamine on rabbit basilar artery were studied and compared with those on other smooth muscles. The drug showed a dose-dependent depressing effect on high-potassium-induced contracture of rabbit basilar artery. The depressing effect was stronger on tonic than on phasic contraction. When phentolamine was applied during high-potassium-induced tonic contraction, dose-dependent relaxation was observed. The degree of phentolamine-induced-relaxation of high-potassium-induced tonic contraction was not affected by surgical denervation of the basilar artery, although catecholamine content was almost completely lost, as indicated by chemical and histochemical experiments. The relaxed tension caused by phentolamine was reversed by addition of Ca in a dose-dependent manner. Verapamil also showed a dose-dependent relaxing effect on high-potassium-induced contracture, with this relaxed tension being reversed by the addition of Ca in a dose-dependent manner. The relaxing effect of phentolamine on rabbit basilar artery was stronger than on rabbit aorta or guinea-pig taenia coli. Phentolamine depressed serotonin- or histamine-induced contraction at a concentration more than 10 times higher than the concentration for depression of noradrenaline-induced contraction. The depression of high-potassium-induced contracture and reversal by additional Ca, especially in denervated preparations, indicates that phentolamine acts directly on smooth muscle in a similar manner to that of Ca antagonists.

Animals↗