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Effect of phentolamine on venous return in human erection.

A group of 25 patients underwent Doppler penile blood examination and cavernometry before and after 5 mg of phentolamine injected intracavernously. The organic or psychogenic nature of impotence was determined by psychological testing, the intracavernous injection of papaverine, hormonal evaluation, neurological examination, Doppler penile blood flow measurement and cavernometry for vascular investigations. The intracavernous injection of phentolamine had no effect on the venous return and it provoked penile arterial dilatation. The erectile angle, which was also measured, was less evident than after the injection of papaverine. The results confirmed the fact that an increase in arterial inflow alone is not sufficient to induce a rigid erection in man.

Humans↗

The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition.

1 Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]-(-)-noradrenaline. The nerves were stimulated with up to 40 trains of 10 pulses every min at 1 Hz, and the evoked increases of [3H-]noradrenaline overflow into the perfusate, of right atrial tension development and ventricular beating frequency were measured. 2 Oxymetazoline inhibited the evoked transmitter overflow (IC50: 10 nM) and decreased the postsynaptic responses in a concentration-dependent manner. It behaved as a full against in abolishing the evoked transmitter overflow. 3 Yohimbine up to 1 microM neither enhanced the evoked [3H]-noradrenaline overflow nor the postsynaptic parameters. Phentolamine (1 microM) caused a transient, minor (less than 30%) increase in [3H]-noradrenaline overflow. 4 Yohimbine (0.03-1.0 microM) and phentolamine (0.1-5.0 microM) shifted to the right the concentration-response curve of oxymetazoline for the inhibition of [3H]-noradrenaline overflow in response to nerve stimulation without depressing the maxima. The pA2 values were 7.82 and 7.52, respectively. 5 Yohimbine (0.1 microM) also antagonized the decrease induced by oxymetazoline in the postsynaptic responses to nerve stimulation. 6 The results confirm the existence of presynaptic inhibitory alpha 2-adrenoceptors at the adrenergic nerve fibres of the rat heart in vitro. Under the stimulation and perfusion conditions selected, the released endogenous transmitter apparently does not activate a negative feedback mechanism, thus permitting the determination of pA2 values.

Animals↗

Reduction by phentolamine of the hypotensive effect of methionine enkephalin in anaesthetized rabbits.

In intact rabbits anaesthetized with pentobarbitone, methionine enkephalin (Met enkephalin, 1-1,000 micrograms kg-1 i.v.) produced a dose-dependent bradycardia and hypotension. The bradycardia and hypotension were antagonized by naloxone hydrochloride (1 mg kg-1), but not by naloxone methobromide (1.3 mg kg-1). Phentolamine (1 and 4 mg kg-1 i.v.) blocked both the hypotension and bradycardia produced by Met enkephalin. The inhibitory effect of phentolamine was not due to a simple hypotensive action of this drug per se because a similar degree of hypotension induced by nitroprusside (15 micrograms kg-1, i.v.) caused a further reduction of pressure when Met enkephalin was added. Atropine (2 mg kg-1) reduced the bradycardia but not the hypotensive response to Met enkephalin. Met enkephalin did not antagonize the vasopressor effect of exogenous noradrenaline (2-8 micrograms kg-1, i.v.). Met enkephalin had no significant effects in superfused thoracic aortic strips and in isolated perfused hearts of rabbits. It is concluded that the cardiovascular effects of Met enkephalin are more probably due to an action on the central nervous system, although a peripheral site of action cannot be completely excluded.

Animals↗

An acute ocular inflammatory reaction induced by intravitreal bovine serum albumin in presensitized rabbits: the effect of phentolamine.

An acute inflammatory reaction in the uvea was challenged by an intravitreal injection of bovine serum albumin (BSA) in presensitized rabbits. During the observation time of 3 h, intraocular pressure (IOP) increased, anterior uveal blood vessels were dilated, miosis was produced, and as a sign of the breakdown of the blood aqueous barrier, protein content in the aqueous humour was increased. In the contralateral eye, the reaction consisted of an increase in IOP and a disruption of the blood aqueous barrier. As an evidence of the immunological mechanism of this acute reaction, presensitized animals intravitreally injected with saline or unimmunized rabbits which were injected with BSA showed no significant changes in IOP, pupillary diameter or protein content in aqueous humour. Phentolamine significantly reduced protein leakage into the anterior chamber of the experimental eye. It also significantly inhibited the increase in IOP and protein leakage in the contralateral eye. The present findings demonstrate that a hypertensive inflammatory phase is present in the acute experimental uveitis. The mechanisms of the reaction and the mode of action of phentolamine are discussed.

Animals↗

Cost utility analysis of sildenafil compared with papaverine-phentolamine injections.

OBJECTIVE: To compare the cost effectiveness of sildenafil and papaverine-phentolamine injections for treating erectile dysfunction. DESIGN: Cost utility analysis comparing treatment with sildenafil (allowing a switch to injection therapy) and treatment with papaverine-phentolamine (no switch allowed). Costs and effects were estimated from the societal perspective. Using time trade-off, a sample of the general public (n=169) valued health states relating to erectile dysfunction. These values were used to estimated health related quality of life by converting the clinical outcomes of a trial into quality adjusted life years (QALYs). PARTICIPANTS: 169 residents of Rotterdam. MAIN OUTCOME MEASURES: Cost per quality adjusted life year. RESULTS: Participants thought that erectile dysfunction limits quality of life considerably: the mean utility gain attributable to sildenafil is 0.11. Overall, treatment with sildenafil gained more QALYs, but the total costs were higher. The incremental cost effectiveness ratio for the introduction of sildenafil was pound sterling 3639 in the first year and fell in following years. Doubling the frequency of use of sildenafil almost doubled the cost per additional QALY. CONCLUSIONS: Treatment with sildenafil is cost effective. When considering funding sildenafil, healthcare systems should take into account that the frequency of use affects cost effectiveness.

Adolescent↗

Phentolamine for vasodilator therapy in left ventricular failure complicating acute myocardial infarction. Haemodynamic study.

In 15 patients with acute myocardial infarction associated with signs of left ventricular dysfunction, phentolamine was infused intravenously in a dose of 10 mg per hour. This therapy induced a substantial reduction in mean right atrial pressure from 10 to 7 mmHg (1.3 to 0.9 kPa) (P) less than 0.001), and in pulmonary capillary wedge pressure from 20 to 13 mmHg (2.7 to 1.7 kPa) (P less than 0.001). The cardiac index increased from 2.5 to 3.0 1/min per m-minus 2 (P less than 0.001) accompanied by a fall in both the systemic and pulmonary vascular resistances (P less than 0.001). On the other hand, the mean stroke work index did not change significantly after phentolamine, because of tar resistance. With the dose used the mean arterial pressure decreased from 112 to 99 mmHg (14.9 to 13.2 kPa) (P less than 0.001). No adverse effects attributable to the drug treatment were noted. Benefits of this treatment are probably related to reduction in the impedance of left ventricular ejection and possibly to its relaxant effect on the venous tone. The drug may also improve subendocardial perfusion by decreasing left diastolic ventricular pressure. This could possibly limit extension of necrosis. Thus vasodilator therapy appears to be of particular interest in left ventricular failure complicating acute myocardial infarction, where inotropic agents may be contraindicated.

Adult↗

Effects of phentolamine on coronary blood flow in patients with recent myocardial infarction.

The myocardial clearance of rubidium may be obtained by praecordial counting after intravenous injection of Rb-minus 86 Cl. Eight patients with recent myocardial infarction had this determination performed before and after the infusion of 10 mg phentolamine at a rate of 0.3 mg/minute. The average predrug myocardial clearance of Rb was 89.3 plus or minus 29.9 ml/min per 100 g myocardium. After phentolamine, the average myocardial clearance rose to 117.3 plus or minus 33.3 ml/min per 100 g myocardium (P LESS THAN 0.01). An explanation for this findings is presented as well as its possible clinical applications.

Adult↗

Interaction of propranolol and phentolamine with ethanol in the rat.

The possible role of the adrenergic nervous system in the intoxicant effects of ethanol was examined in studies of the interaction or propranolol and phentolamine with ethanol. Propranolol teneded to increase the effect of lower doses of ethanol in a dose-dependent manner. However, the effect of higher doses of ethanol (over 2.0 g/kg) tended to be diminished by low doses of propranolol, whereas higher doses of propranolol were ineffective or actually increased the ethanol effect. Phentolamine tended to decrease the effect of the lower ethanol doses. These findings are inconsistent with any simple adrenergic mechanism in the mediation of the intoxicant effect of ethanol.

Animals↗

The effects of propranolol, phentolamine, and atropine on canine coronary vascular gradients.

The objective of this study was to measure pressure gradients in the coronary circulation following the administration of three receptor-blocking drugs, propranolol, phentolamine, and atropine when administered singly and in sequence. As well, we examined the responses of these gradients to eight interventions: left stellate ganglion or left vagosympathetic trunk stimulation, administration of isoproterenol, acetylcholine, noradrenaline, adenosine, phenylephrine, or adrenaline. Using a multiple linear regression model we examined the actions and interactions of the receptor-blocking agents on hemodynamic variables and vascular gradients. Propranolol reduced heart rate as expected and blocked the responses to isoproterenol administration. As well, it abolished the epicardial coronary artery diastolic gradient. The gradient was restored when propranolol was the second receptor blocker administered but was abolished when it was the third. Phentolamine induced vasodilation with a decrease in coronary small vessel gradients. This effect persisted without regard to the sequence of administration. When it was the second or third agent it decreased the microcirculation and small vein gradients, an action it did not manifest when given singly. Atropine singly did not alter pressures or gradients; but as the second agent it altered the transmural, outflow tract, epicardial diastolic, and microcirculation and small vein diastolic gradients; and as the third agent the changes were in the transmural, epicardial systolic and diastolic, and small artery systolic and diastolic gradients. The pattern of responses was not predictable and that indicates that unique changes occur in the responses of the coronary circulation when multiple receptor-blocking agents are employed. Adrenergic control tends to dominate in the coronary arterial circulation, and muscarinic control in the coronary microcirculation and veins with considerable overlap.

Adenosine↗

Norepinephrine, phentolamine and buflomedil influence on arteriolar vasomotion in the hamster skinfold preparation.

Vasomotion is a potential target for drugs in vascular diseases. In this work, the effects on arteriolar vasomotion of norepinephrine, phentolamine and the vasoactive drug buflomedil were assessed in the hamster skinfold preparation. Results show the strong vasokinetic properties of alpha-sympathetic receptor activation by norepinephrine and an expected depressive effect of the alpha-blocker phentolamine. Buflomedil 10(-4) M enhances vasomotion and arteriolar reactivity and does not interfere with norepinephrine. The mechanism of these properties of buflomedil remains to be investigated.

Animals↗

Phentolamine therapy in severe chronic asthmatiform bronchitis.

Continuous phentolamine infusion for 3 days in 6 patients with severe chronic bronchial obstruction produced a marked improvement in subjective well-being and arterial blood gas values. Ventilatory function and pulmonary arterial pressure remained virtually unchanged but a chronic oral corticosteroid therapy could be substantially reduced during 4 weeks of oral treatment with phentolamine 100 mg three times daily.

Adult↗

Effect of prazosin on the cardiopulmonary response to dopamine in awake lambs: comparison with phentolamine and tolazoline.

Combination vasodilator and cardiotonic therapy may help infants with pulmonary vasospasm and low cardiac output. We previously have shown that the alpha 1- and alpha 2- blocking agents tolazoline and phentolamine, plus dopamine, improved cardiac output relative to dopamine alone, without changing pulmonary vascular resistance. To similarly test an agent with selective alpha 1-receptor blocking action, prazosin, we instrumented 6 newborn lambs to measure the pressure in the pulmonary artery, aorta and left atrium and cardiac output. After recovery, the lambs were studied while awake and breathing room air. The response to dopamine, at doses of 2.7, 27 and 270 micrograms/kg/min, was measured alone, and again on a different day after prazosin (1 mg/kg). Dopamine alone raised systemic, pulmonary and left atrial pressure, and systemic vascular resistance at high doses. Pulmonary vascular resistance did not change. Prazosin prevented the dopamine-induced systemic resistance increase and permitted cardiac output to rise relative to dopamine alone (p less than 0.0125), but barely blunted the dopamine-induced pulmonary pressure increase (p less than 0.005 vs. base in both groups). These results are similar to those previously found with tolazoline and phentolamine. Thus, all the tested alpha-blockers facilitate the cardiotonic effect of dopamine, but none ablates its pulmonary pressure effect.

Animals↗

Hemodynamic effects of phentolamine in valvular abnormalities.

Seven patients with mitral insufficiency and seven patients with aortic insufficiency were studied by right and left heart catheterization. Hemodynamic observations were made during a control period and during the infusion of phentolamine. Significant declines in the pulmonary artery mean pressure, left ventricular end diastolic pressure, peripheral resistance, and arteriovenous oxygen difference were seen in both groups. The cardiac index increased significantly in the two groups. Phentolamine therapy produced favorable hemodynamic effects because of its vasodilating action as well as its positive inotropic effects.

Aortic Valve Insufficiency↗

Left ventricular wall motion improvement after phentolamine: a case report.

Left ventricular wall motion abnormalities are commonly seen in coronary artery disease patients. The differentiation between reversibly ischemic areas an irreversibly damaged areas is 1 was of predicting which patient might gain improved ventricular function from surgical correction. One patient with coronary artery disease is presented here who showed poor septal movement on his echocardiogram. After the IV administration of phentolamine, the septal movement became normal. Thus, phentolamine should be considered as an agent that can detect reversible areas of wall motion abnormalities.

Coronary Disease↗

Intracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic.

A total of 160 men with erectile failure received treatment with 13,030 intracavernosal papaverine and phentolamine injections as outpatients. One-hundred-and-fifteen (72%) achieved an erection sufficient for sexual intercourse and after a mean follow-up period of 14.1 months, 55 (48%) are still attending and successfully using intracavernous therapy. Sixteen patients had a total of 22 episodes of priapism and one patient developed corporeal fibrosis. We conclude that intracavernous papaverine and phentolamine is an effective therapy for erectile failure in a genitourinary clinic.

Adult↗

The sites of action of estradiol and phentolamine in the inhibition of the pulsatile, circhoral discharges of LH in the rhesus monkey (Macaca mulatta).

Pulsatile LH secretion was re-established in ovariectomized monkeys bearing hypothalamic lesions by an intermittent infusion of LHRH. The administration of estradiol to such animals resulted in a prompt cessation of these pulsatile discharges of LH and a resultant decline in the mean plasma concentration of the gonadotropin. The time course of this inhibition of LH secretion was indistinguishable from that observed after estrogen administration to ovariectomized animals with intact nervous systems. In contrast, phentolamine did not interrupt the pulsatile LH discharges occasioned by the hourly administration of exogenous LHRH to the lesioned animals. These results are consistent with the conclusion that the acute negative feedback action of estradiol on circhoral LH release in the monkey is at the level of the pituitary gland, whereas the inhibitory action of phentolamine on this mode of LH secretion is at a neural site.

Animals↗

Suppression of mediobasal hypothalamic gonadotropin-releasing hormone and plasma luteinizing hormone pulsatile patterns by phentolamine in ovariectomized rhesus macaques.

In gonadectomized animals, pulses of LH are secreted concurrently with pulsatile hypothalamic GnRH and it is hypothesized that pulses of GnRH are either driven or modulated by episodes of catecholamine release. The objective of this study was to determine if the alpha-adrenergic antagonist phentolamine (PHEN) can simultaneously block the release of GnRH and LH in ovariectomized (OVX) rhesus macaques. In Exp 1, simultaneous peripheral blood and mediobasal hypothalamic push-pull perfusion (PPP) samples were collected remotely at 10-min intervals for 24 h via a swivel/tether device in eight conscious, freely moving OVX rhesus monkeys. Phentolamine was continuously infused iv for 6 h at the rate of 4 mg/kg BW.h in five animals and 20 mg/kg BW.h in three animals. Infusion started at 6 h after the commencement of PPP. Sampling of PPP and blood continued for 12 h after the cessation of PHEN infusion. Exp 2 was carried out to determine if PHEN affects pituitary responsiveness to exogenous GnRH under conditions similar to those in Exp 1. Exogenous GnRH (5 micrograms, iv) was injected as a single bolus at 10-h intervals before, during, and after either a saline (4 ml/h for 6 h) infusion or, 3 weeks later, a PHEN infusion (4 mg/kgBW.h for 6 h) in three OVX females. The results of Exp 1 show that pulsatile patterns of hypothalamic GnRH and LH were either dampened or abolished by PHEN infusion. During the recovery period after PHEN infusion, pulse amplitudes of LH were enhanced, but pulse amplitudes of endogenous GnRH did not differ, as compared to those of corresponding LH and GnRH before infusion of PHEN. Data from Exp 2 suggested that the alpha-adrenergic blocking agent had no effect on the pituitary LH response to exogenous GnRH administration. These results directly support the hypothesis that adrenergic neuronal activities are critical for the pulsatile release of hypothalamic GnRH which governs the pulsatile release of LH in gonadectomized animals.

Animals↗