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At least 829 records · Page 46Linked to original sources
PubMed1984

Transmitter release modulated by alpha-adrenoceptor antagonists in the rabbit mesenteric artery: a comparison between noradrenaline outflow and electrical activity.

Effects of alpha-adrenoceptor blockers (prazosin, yohimbine, phentolamine and phenoxybenzamine) on the outflow of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) during perivascular nerve stimulation were observed in relation to electrical events in the rabbit mesenteric artery. Cocaine or imipramine increased the NA outflow and reduced the DOPEG outflow induced by nerve stimulation. In the absence of stimulation, cocaine and imipramine did not significantly modify the NA and DOPEG outflows. The alpha-adrenoceptor blockers we used enhanced the NA and DOPEG outflow during nerve stimulation, in a dose-dependent manner; the potency of the enhancement was higher for phentolamine and phenoxybenzamine than for prazosin and yohimbine. Higher concentrations (10(-5) M) of yohimbine reduced the NA and DOPEG outflows induced by nerve stimulation. Prazosin increased the DOPEG outflow in the absence of stimulation, and this effect was not inhibited by pretreatment with cocaine. Guanethidine increased the NA and DOPEG outflow in the absence of stimulation, and the NA outflow was reduced during nerve stimulation. These effects of guanethidine were prevented by pretreatment with cocaine or imipramine. Perivascular nerve stimulation evoked excitatory junction potentials (e.j.ps) and with high frequency stimulation, slow depolarization and spike potentials. Application of phentolamine, phenoxybenzamine or yohimbine enhanced, and of prazosin had no effect, on the amplitude of the e.j.p. Spike potentials were not affected by these alpha-adrenoceptor blockers. Slow depolarization ceased in the presence of prazosin, phentolamine or phenoxybenzamine, and was slightly inhibited by yohimbine. Guanethidine blocked all of these electrical responses induced by perivascular nerve stimulation. Application of prazosin, phentolamine or phenoxybenzamine did not alter the resting membrane potential of the smooth muscle cells. Depolarizations of smooth muscle membrane produced by exogenously applied NA were inhibited by prazosin, phentolamine or phenoxybenzamine. Yohimbine itself depolarized the membrane and the inhibitory effects on the NA-induced depolarization were weaker. We conclude that the smooth muscle membrane of the rabbit mesenteric artery possesses alpha 1-adrenoceptors. Increase in NA outflow by alpha-adrenoceptor antagonists during nerve stimulation was not always consistent with increase in e.j.p. amplitude, presumably due to involvement of actions other than alpha-adrenoceptor blockade with each of these antagonists.

Adrenergic alpha-Antagonists↗
PubMed1989

[Effects of intracisternal injection of naloxone on the depressor response to stimulation of renal afferent nerve in rabbits].

The purpose of this study was to observe the effects of opioid receptor and alpha-adrenergic receptors in the lower brain stem on the depressor response to electrical stimulation of renal afferent nerve, using intracisternal injection of blockers of these receptors. Experiments were conducted in sodium pentobarbital-anesthetized rabbits. The intracisternal injection (ict) of artificial cerebrospinal fluid (CSF) did not greatly affect the depressor response to stimulation of renal afferent nerve (RAS) and of aortic nerve (ANS). Ict of 550 nmol naloxone significantly inhibited the depressor response to RAS (P less than 0.05) but enhanced the depressor response to ANS (P less than 0.05). Ict of 335 nmol phentolamine significantly inhibited the depressor response to both RAS and ANS. Ict of naloxone reversed the phentolamine inhibition of the depressor response to ANS but did not affect the phentolamine inhibition of the depressor response to RAS. Ict of both naloxone and phentolamine did not affect the inhibitory interaction between the RAS-induced depressor and aortic baroreflex. Ict of phentolamine significantly decreased MAP, and ict of naloxone did not decrease MAP but reversed the decrease in MAP by ict of phentolamine. These data suggest that the activation of opioid receptors in the lower brain stem enhances the depressor response to RAS and attenuates the depressor response to ANS. Moreover, activation of alpha-adrenergic receptors in the lower brain stem facilitates the depressor response to RAS and ANS.

Animals↗
PubMed1981

Role of released catecholamines in the vascular response to injected angiotensin II in the dog.

The contribution of released epinephrine and norepinephrine to the pressor response induced by i.v. injected angiotensin II was assessed in pentobarbital-anesthetized dogs. Control pressor dose-response curves for i.v. angiotensin II were obtained in dogs pretreated with hexamethonium, atropine and practolol. Hexamethonium and atropine minimized the cardiovascular reflex responses elicited by the pressor action of angiotensin II which would preclude interpretation of the results. Practolol was administered to antagonize indirect cardiac stimulation selectively through sympathoadrenal activation by angiotensin II. Three additional pressor dose-response curves for angiotensin II were obtained in each dog. The second dose-response curve was obtained after the administration of phentolamine and the third dose-response curve was obtained after the subsequent administration of sotalol. The final dose-response curve was obtained after partial recovery of the pressor responsiveness to norepinephrine and epinephrine from phentolamine blockade. The pressor responses for angiotensin II after phentolamine and sotalol (curve 3) were significantly smaller than those in the control dose-response curve (curve 1). No significant differences in the pressor responses to angiotensin II were noted after phentolamine when compared with those obtained after phentolamine plus sotalol (curve 2 vs. curve 3). The angiotensin II pressor responses after partial recovery from phentolamine (curve 4) did not differ significantly from those obtained in the control dose-response curve. These results of released catecholamines mediated through alpha adrenergic receptors in the pressor response to angiotensin II.

Adrenal Medulla↗
PubMed1977

Central and peripheral adrenergic mechanisms regulating gastric secretion in the rat.

Subcutaneous injection of sympathomimetic agents reduced gastric secretion in pylorus-ligated rats, and the decreasing order of activity was: isoproterenol, norepinephrine, naphazoline and phenylephrine. The effect of naphazoline and phenylephrine was antagonized with 4 mg/kg s.c. of phentolamine, and that of isoproterenol with 4 mg/kg s.c. of propranolol. Thus there exist separate, alpha and beta adrenergic receptors which control gastric secretion in the rat. Intracerebroventricular (i.c.v.) injection of the sympathomimetic agents also reduced secretion, naphazoline being the most potent. The ED50 of i.c.v. naphazoline was 12.3 times less than that of s.c. dose. The antisecretory effect of i.c.v. naphazoline was antagonized with i.c.v. phentolamine (0.016 and 0.064 mg/kg), but not with propranolol. These results suggest that naphazoline stimulates central alpha adrenergic receptors which has a tonic inhibiting role in rat gastric secretion. Analogous to the results with naphazoline, i.c.v. phentolamine, but not propranolol, blocked an antisecretory effect of chlorpromazine. Phentolamine administered s.c. also reduced the antisecretory activity, but the dose required for the antagonism was 250 times that of i.c.v. phentolamine. An antisecretory effect of imipramine was not blocked by phentolamine or propranolol. These results suggest that an activation of central alpha adrenergic receptors is important for the antisecretory effect of chlorpromazine.

Animals↗
PubMed1989

An insulin-releasing property of imidazoline derivatives is not limited to compounds that block alpha-adrenoceptors.

As we have demonstrated previously phentolamine stimulates the release of additional insulin from isolated mouse islets and raises plasma insulin levels in the whole rat. This effect was independent of the well known property of phentolamine to block alpha-adrenoceptors. In experiments on isolated pancreatic islets from mice we now demonstrate that tolazoline and antazoline which are chemically closely related to phentolamine, share its ability to potentiate insulin release. The following results were taken as evidence that this effect does not result from an alpha-adrenoceptor blocking action of imidazoline compounds. More than 10 times higher concentrations of phentolamine were required to liberate additional insulin from isolated islets than were effective in counteracting the inhibitory effect of clonidine on insulin release. The newly introduced alpha 2-adrenoceptor antagonist BDF 8933, which is an imidazoline derivative, stimulates insulin release as well, while the irreversible alpha-adrenoceptor blocking agent benextramine of different structure failed to do so, even when being present in concentrations blocking the alpha 2-adrenoceptor-mediated effects of clonidine. Antazoline shared the ability of phentolamine to stimulate insulin release despite having no or only very little alpha-adrenoceptor blocking activity. When used under our conditions, it almost entirely failed to alleviate the inhibition of insulin release induced by clonidine. We conclude that the response of the islet cells to imidazoline derivatives is not limited to those capable of blocking alpha-adrenoceptors. On the other hand, alpha-adrenoceptor blocking agents of different chemical structure fail to induce the release of additional insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Role of vascular adrenergic mechanisms in the haemodynamic and PGI2 stimulating effects of angiotensin in diabetic dogs.

In aware of the well-known altered vascular responsiveness in the diabetic vasculature, this study aimed to compare the haemodynamic and PGI2 releasing effects of angiotensin in metabolically healthy (12) and alloxan-(560 umol/kg) diabetic (12) dogs as well as to analyze the role of vascular adrenoceptors in this. In vivo the effect of intracoronarially administered angiotensin (63-125-250-500-1000 pmol/kg/min) on coronary blood flow, mean arterial blood pressure, myocardial contractile force and heart rate was investigated without and with pretreatment of 2 umol/kg phentolamine. In vitro PGI2 release by isolated coronary rings was induced by 50 nmol/l angiotensin before and after pretreatment with 5 umol/l phentolamine and measured by radioimmunoassay. Angiotensin enhances dose-dependently both the mean arterial blood pressure and coronary blood flow, while it provokes a considerable (p < 0.05) increase of PGI2 formation by isolated coronary arterial rings. These alterations could be prevented by phentolamine administration both in vivo and in vitro, while this drug did not affect the angiotensin-induced enhancement of diabetic coronary blood flow. On the other hand the increase of blood pressure by angiotensin was found to be more (p < 0.05) expressed in diabetes and it could be further potentiated by phentolamine. PGI2 synthesis by isolated diabetic coronary rings could not be modified either by angiotensin alone or in combination with phentolamine. On the basis of above data, the lack of stimulated vascular PGI2 formation mediated by alpha-adrenergic mechanisms is supposed to causatively contribute to the diminished sensitivity of diabetic coronary arteries to vasodilation.

Angiotensin II↗
PubMed1976

Relationship between the level of cAMP and the contractile force under stimulation of alpha- and beta-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle.

The time course of changes of the level of 3',5'-cyclic AMP (cAMP) and of the tension developed under stimulation of alpha- and beta-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the dose-response relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10(-5) M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36% respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When alpha-adrenoceptors were blocked by phentolamine (10(-6) M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10(-5) M) both on the level of cAMP and the developed tension mediated via stimulation of beta-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10(-6) M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the alpha-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10(-5) M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of beta-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (less than 10(-5) M) induced by stimulation of alpha-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of beta-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Endogenous noradrenaline as modulator of hippocampal serotonin (5-HT)-release. Dual effects of yohimbine, rauwolscine and corynanthine as alpha-adrenoceptor antagonists and 5-HT-receptor agonists.

The modulation of hippocampal serotonin (5-HT)-release by noradrenaline was studied in rabbit hippocampal slices, which were preincubated with 3H-serotonin and then superfused continuously. Electrical field stimulation of the slices elicited a tritium overflow, which was decreased by clonidine in a concentration dependent manner. Phentolamine antagonized the effects of clonidine and, given alone, increased the evoked tritium overflow. This facilitatory effect of phentolamine was further enhanced in the presence of (+)oxaprotilin, a highly selective noradrenaline uptake inhibitor, whereas the (-)enantiomer of oxaprotilin, which does not affect noradrenaline uptake, was inactive. (+)Oxaprotilin but not (-)oxaprotilin, given alone, inhibited the evoked tritium overflow. The inhibitory effect of (+)oxaprotilin was antagonized by phentolamine. In the presence of phentolamine, the alpha-adrenoceptor antagonists yohimbine, rauwolscine and corynanthine decreased the evoked 5-HT-release concentration dependently. Their inhibitory effects were, however, abolished (corynanthine) or inversed to a facilitation of release (yohimbine, rauwolscine) if instead of phentolamine the 5-HT-receptor antagonist metitepin was present. Therefore we suggest that yohimbine, rauwolscine and corynanthine, in addition to their alpha-adrenoceptor antagonistic properties, may act as agonists at 5-HT-autoreceptors. Possibly the indol part of their molecules is responsible for this effect. Furthermore, our results provide evidence for the modulation of hippocampal 5-HT-release by endogenous noradrenaline.

Animals↗
PubMed1980

Alpha-adrenoceptor-mediated modulation of 5-hydroxytryptamine release from rat brain cortex slices.

Slices of rat brain cortex preincubated with 3H-5-hydroxytryptamine were superfused with physiological salt solution and stimulated electrically, or they were superfused with Ca2+-free solution containing 25 mM K+ and stimulated by introduction of 1.3 mM CaCl2 for 2 min. 1. The electrically evoked 3H overflow was decreased by noradrenaline and increased by phentolamine in a concentration-dependent manner. 2. Phentolamine caused a parallel shift to the right of the concentration-response curve of noradrenaline for its inhibitory effect on impulse-evoked 3H overflow; by contrast, it left the inhibitory effect of unlabelled 5-hydroxytryptamine on the electrically evoked 3H overflow unaffected. 3. Propranolol did not alter the inhibitory effect of noradrenaline on impulse-induced 3H overflow. 4. The increasing effect of phentolamine on the electrically evoked 3H overflow was not modified by paroxetine. 5. Cocaine (at a concentration which almost completely blocks the uptake of 3H-noradrenaline but only partially that of 3H-5-hydroxytryptamine into cortex slices) decreased impulse-evoked 3H overflow. This effect was abolished by phentolamine. 6. In the presence of tetrodotoxin throughout superfusion, the Ca2+-evoked 3H-overflow from slices superfused with Ca2+-free solution was inhibited by noradrenaline and increased by phentolamine. These findings suggest that the terminal serotoninergic fibers of rat brain cortex possess alpha-adrenoceptors, activation of which by exogenous or endogenous noradrenaline leads to inhibition of the release of 5-hydroxytryptamine.

Animals↗
PubMed1991

Possible role of adrenergic mechanism in starvation-induced reduction in circulating thyroxine and triiodothyronine in rats.

To elucidate the possible role of adrenergic mechanism in thyroid hormone metabolism during starvation, serum thyrotropin (TSH), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels and conversion of T4 to T3 in perfused liver were investigated in fasting (60 h) and fed rats. Propranolol (0.5 mg/kg), yohimbine (0.3 mg/kg) or phentolamine (5.0 mg/kg) was subcutaneously injected to the rat every 12 h. Serum levels of TSH, T4, and T3 were significantly lower in fasting rats than in fed rats. Although propranolol, yohimbine, and phentolamine administration did not significantly alter circulating TSH, T4 and T3 levels in fed rats, phentolamine partly inhibited the starvation-induced reduction in circulating TSH, T4, and T3. Thyroxine uptake and T3 production in perfused liver were significantly lower in fasting rats than in fed rats. Phentolamine treatment did not alter the T4 uptake and T3 production in perfused liver of fasting rats. These results suggest that alpha-adrenergic mechanism may have some role in starvation-induced reduction in circulating T4 and T3, and that phentolamine partly inhibited this phenomenon probably through the inhibitory effect on reduction in circulating TSH during starvation.

Animals↗
PubMed2001

Alpha2-adrenoceptor-mediated inhibition of cultured sympathetic neurons: changes in alpha2A/D-adrenoceptor-deficient mice.

Alpha2-Adrenoceptor-mediated inhibition of [3H]noradrenaline release and alpha2-adrenoceptor-mediated inhibition of voltage-activated Ca2+ currents were compared in cultured thoracolumbar postganglionic sympathetic neurons from newborn wildtype (WT) mice and mice in which the alpha2A/D-adrenoceptor gene had been disrupted (alpha2A/DKO). In cultures prepared from WT mice and preincubated with [3H]noradrenaline, the alpha2-adrenoceptor agonist 5-bromo-6-(2-imidazolidinylidenamino)quinoxaline (UK 14,304) reduced the (autoinhibition-free) release of [3H]noradrenaline elicited by single electrical pulses or trains of 8 pulses at 100 Hz. The maximal inhibition by UK 14,304 amounted to 70%-85%. Its concentration-response curve was shifted to the right by phentolamine (0.3 microM) and, to a smaller extent, rauwolscine (0.3 microM). Pretreatment of the cultures with pertussis toxin abolished the effect of UK 14,304. Phentolamine and rauwolscine increased the (alpha2-autoinhibited) release of [3H]noradrenaline elicited by 18, 36 or 72 pulses at 3 Hz. In cultures from alpha2A/DKO mice, UK 14,304 failed to reduce the release of [3H]noradrenaline elicited by single pulses and phentolamine and rauwolscine failed to increase the release of [3H]noradrenaline elicited by 18-72 pulses at 3 Hz. In neurons from WT mice examined with the amphotericin B-perforated configuration of the patch clamp method, UK 14,304 reduced depolarisation-evoked Ca2+ currents. The inhibition was voltage-dependent as shown by a decline at strong depolarisation during ramp-like voltage commands and by an attenuation briefly after a conditioning depolarising pulse. The maximal inhibition by UK 14,304 was 39%. Its concentration-response curve was shifted to the right by phentolamine (0.3 microM) but not significantly changed by rauwolscine (0.3 microM) and prazosin (1 microM). Pretreatment with pertussis toxin abolished the effect of UK 14,304. In neurons from alpha2A/DKO mice, UK 14,304 also reduced depolarisation-evoked Ca2+ currents, but with a smaller maximal effect, namely 18% inhibition. Its concentration-response curve was shifted to the right by rauwolscine (0.3 microM) and prazosin (1 microM) but not significantly changed by phentolamine (0.3 microM). Pretreatment with pertussis toxin abolished the effect of UK 14,304 also in cultures from alpha2A/DKO mice. It is concluded that the only presynaptic alpha2-autoreceptors that detectably depress transmitter release from cultured thoracolumbar sympathetic neurons taken from newborn mice are alpha2A/D. In contrast, the soma-dendritic alpha2-autoreceptors that inhibit voltage-gated Ca2+ channels are both alpha2A/D and non-alpha2A/D (i.e. alpha2B or alpha2c). Both presynaptic alpha2A/D- and soma-dendritic alpha2A/D- and non-alpha2A/D-autoreceptors operate through pertussis toxin-sensitive G proteins in these neurons.

Adrenergic alpha-Agonists↗
PubMed1987

Characterization of alpha 2-adrenergic receptors of calf retina membranes by [3H]-rauwolscine and [3H]-RX 781094 binding.

Alpha 2-adrenergic receptors were identified in calf retina membranes by binding of the radiolabelled antagonists [3H]-RX 781094 and [3H]-rauwolscine. When 10 microM phentolamine was used to determine the non-specific binding, both radioligands labelled a single class of non-cooperative sites: Bmax = 1051 +/- 252 fmol/mg protein, Kd = 5.1 +/- 1.5 nM for [3H]-RX 78104 and Bmax = 1167 +/- 449 fmol/mg protein, Kd = 21.0 +/- 4.1 nM for [3H]-rauwolscine. Competition binding experiments showed the typical pharmacological potency order of alpha 2-adrenergic receptors, i.e. phentolamine greater than yohimbine greater than prazosin. Agonist competition binding curves revealed the presence of two receptor populations, having respectively high affinity (70% of the total receptor population) and low affinity for agonists, but with the same affinity for the antagonists. The high affinity sites could be converted into low affinity sites by guanine nucleotides. The non-specific binding of [3H]-RX 781094 was the same if 0.1 mM (-)-epinephrine was used instead of phentolamine. In contrast, the non-specific binding of [3H]-rauwolscine was markedly lower with (-)-epinephrine than with phentolamine. Under this condition, the Scatchard plot of [3H]-rauwolscine saturation binding was curvilinear, indicating the presence of low affinity sites for the radioligand in addition to alpha 2-adrenergic receptors. Competition binding experiments revealed that these low affinity sites were distinct from adrenergic receptors: the catecholamine agonists (-)- and (-)-epinephrine, (-)-norepinephrine, (-)-isoproterenol and dopamine competed with similar Ki values (microM range) whereas clonidine did not interact. Furthermore, these sites bound reserpine and the alpha 2-adrenergic antagonists yohimbine and rauwolscine but not phentolamine.

Animals↗
PubMed1992

The effect of some alpha-adrenoceptor antagonists on spontaneous myogenic activity in the rat portal vein and the putative involvement of ATP-sensitive K+ channels.

In the present study we showed that the alpha-adrenoceptor antagonists phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively applied in high concentrations (1-100 mumol/l), can increase spontaneous myogenic activity in the rat portal vein. 5-Methyl-urapidil and rauwolscine were ineffective in this respect. Pretreatment with phenoxybenzamine in a concentration of 1 mumol/l (20 min), which results in alkylation of all functional alpha-adrenoceptors in the rat portal vein, was unable to antagonize the increase in spontaneous myogenic activity elicited by phentolamine. Antazoline (1-100 mumol/l), a H1 antagonist and 2-substituted imidazoline which is devoid of alpha-adrenoceptor blocking properties, exhibited similar effects on spontaneous myogenic activity as its structurally closely related analogue phentolamine. Since phentolamine is reported to interact with ATP-sensitive K+ channels we investigated the role of K+ channels in more detail. The K+ channel openers cromakalim and diazoxide elicited a decrease in spontaneous myogenic activity. Glibenclamide (0.3-3 mumol/l), a selective blocker of ATP-sensitive K+ channels in cardiac and pancreatic tissues, and phentolamine (1-10 mumol/l) shifted the concentration-response curves of cromakalim and diazoxide concentration dependently to the right. Yohimbine showed only a modest effect in the highest concentration (100 mumol/l) applied. E-4031 (0.01-0.3 mumol/l), a sotalol derivative and one of the most selective blockers of the delayed rectifier current (Ik) in cardiac tissue, was a potent contractile agent when added to the rat portal vein in the same way as the alpha-adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

The effect of adrenergic blockade on glucose-induced thermogenesis.

The effect of alpha, beta, or combined sympathetic blockade on the increase in energy expenditure and concentrations of norepinephrine, glucose, and insulin following oral intake of 100 g of glucose was studied in lean subjects. Alpha blockade with intravenous (IV) phentolamine (n = 5) infusion increased oxygen consumption after glucose ingestion but no more than it increased the oxygen consumption when no glucose was given. Beta blockade with IV propranolol (n = 13) and combined alpha and beta blockade (n = 6) did not affect basal metabolic rate or the increase in metabolic rate after glucose ingestion. Phentolamine or combined propranolol plus phentolamine administration markedly increased plasma norepinephrine concentrations. Basal glucose and insulin concentrations were not affected by any of the infused drugs. Glucose-stimulated insulin concentrations were unchanged by propranolol and combined blockade, whereas there was a trend (P = 0.07) toward an increased response to glucose during phentolamine administration. These data do not support a role for the sympathetic nervous system in the increase in metabolic rate following glucose ingestion. The increase in metabolic rate during phentolamine administration can be attributed to beta adrenergic stimulation.

Adolescent↗
PubMed1985

Dissociation of epinephrine's hyperglycemic and anorectic effect.

The contributions of alpha- and beta-adrenergic receptor mechanisms to epinephrine-induced hyperglycemia, to prandial hepatic glycogenolysis, and to epinephrine-induced inhibition of feeding were investigated in rats, because epinephrine's hyperglycemic and anorectic effect might be related to each other. Intraperitoneal injection of the selective alpha-adrenergic receptor antagonist phentolamine (0.5 mg/kg body weight) but not of the selective beta-adrenergic receptor antagonist propranolol (0.5 mg/kg body weight) reduced the hyperglycemic effect of a subsequent epinephrine injection (0.05 mg/kg body weight). In addition, injection of phentolamine (0.5 mg/kg b.w.) or injection of phentolamine plus propranolol (0.5 mg/kg b.w. each) similarly inhibited epinephrine-induced hepatic glycogenolysis. In contrast, phentolamine injection did not affect prandial hepatic glycogenolysis. Neither phentolamine nor propranolol injection was sufficient to affect the inhibition of feeding induced by subsequent epinephrine injection, but the combination of both receptor blockers completely abolished epinephrine's effect on food intake. These findings are not consistent with the idea that epinephrine-induced hypophagia is related to epinephrine's effect on hepatic carbohydrate metabolism. In addition, the data suggest that catecholamines are not the main contributors to prandial hepatic glycogenolysis in rats.

Animals↗
PubMed1983

Mechanisms involved in the blocking effects of pimozide on smooth muscle contraction.

Pimozide, a dopamine-receptor antagonist, shifted to the right the concentration-response curves (CRC) induced by (-)-noradrenaline in the isolated posterior mesenteric artery of the cat. Since this antagonism could be related to a blockade of vascular alpha-adrenoceptors, we compared the effects of pimozide (0.20 microM) with those of phentolamine (0.31 microM). The onset of the blockade by pimozide on the (-)-noradrenaline-induced contractions was slower when compared with that of phentolamine. In addition, the effects of pimozide did not reverse by washing while those of phentolamine did. Pimozide but not phentolamine inhibited the contractions elicited by potassium and it decreased the maximum responses of the curves. This effect was partially reversed by CaCl2 10.2 mM. Pimozide displaced the CRC induced by CaCl2 to a greater extent than phentolamine. Even if a blocking effect on alpha-adrenoceptors cannot be discarded, our results suggest that pimozide may interfere with calcium in the arterial smooth muscle. Furthermore, vascular smooth muscle seems to be more sensitive than non-vascular tissue to the action of pimozide.

Animals↗
PubMed2004

Alpha-adrenergic receptor blockade and hyperaemic response in patients with intermediate coronary stenoses.

BACKGROUND: Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced alpha-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. AIM: To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. METHODS AND RESULTS: Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50+/-1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an alpha1-, alpha2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective alpha1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46+/-0.06 vs. 1.47+/-0.06 mm, ns), urapidil (1.46+/-0.06 vs. 1.39+/-0.08, ns), and saline (1.56+/-0.08 vs. 1.55+/-0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79+/-0.02 vs. 0.77+/-0.02, p<0.05; urapidil: 0.78+/-0.02 vs. 0.75+/-0.02, p<0.05). However, only 6 patients showed a change in FFR from > or = 0.75 to <0.75 and no patients showed a change in FFR from > or = 0.80 to <0.75 that could have influenced clinical decision making. Saline did not induce any change in FFR. Phentolamine and urapidil induced only transient and negligible haemodynamic changes in heart rate and blood pressure. CONCLUSIONS: The administration of alpha-adrenergic blockers in addition to adenosine unmasks a small, yet clinically irrelevant, degree of residual microvascular tone. The consequential changes in FFR values do not significantly affect clinical decision making.

Adrenergic alpha-Antagonists↗
PubMed1976

A comparison of the hemodynamic effects of inotropic agents.

This experimental study was conducted to compare and contrast the cardiovascular effects of the drugs most commonly used to alleviate low-cardiac-output syndrome. Twenty-five adult mongrel dogs were infused with sodium pentobarbital (60 mg/min) until their cardiac output fell to 50+/-5% of the average control values determined by thermodilution technique prior to pentobarbital infusion. The dogs were then divided into six groups, and one of the following agents or combinations of agents was administered to each group: isoproterenol, glucagon, dopamine, dobutamine, levarterenol and phentolamine, or levarterenol and nitroprusside. All drugs, except for glucagon and the combination of levarterenol and nitroprusside, produced an increase in cardiac output above the nonfailure baseline values. However, this increase was accompanied by an undesirable, pronounced tachycardia except when levarterenol was used simultaneously with phentolamine. Both dopamine and the combined infusion of levarterenol and phentolamine proved the most effective in restoring systemic arterial pressure to near baseline values, and both were able to increase renal blood flow above the failure baseline values. While renal blood flow remained elevated with all dosages of levarterenol and phentolamine, it tended to decrease with larger doses of dopamine. These experiments demonstrate that there are major advantages in the use of simultaneously infused levarterenol and phentolamine for control of low-cardiac-output syndrome: increased cardiac output without elevated peripheral vascular resistance, restoration of systemic arterial pressure and consequent improved coronary flow, absence of tachycardia, and augmented renal blood flow.

Animals↗