Α-adrenergic Blockade Research Articles

Testing the Link between Sympathetic Efferent and Sensory Afferent Fibers in Neuropathic Pain

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic α-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done inrandom order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P > 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that α-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP.

Non‐alpha‐adrenergic effects on systemic vascular conductance during lower‐body negative pressure, static exercise and muscle metaboreflex activation

This study tested the hypothesis that non-α-adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex-specific manner during the sympathoexcitatory manoeuvres. Twelve healthy subjects underwent lower-body negative pressure (LBNP, -40mmHg) as well as static handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm circulatory occlusion (PECO, 5min each) with and without α-adrenergic blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure and superficial femoral artery blood flow were measured to calculate cardiac output, SVC and leg vascular conductance (LVC) during the last minute of each intervention. Mean arterial pressure (MAP) decreased more during LBNP with PHE compared with saline (-7±7 vs. -2±5%, P=0.016). PHE did not alter the MAP response to HG (+20±12 and +24±16%, respectively, for PHE and saline) but decreased the change in MAP during PECO (+12±7 vs. +21±14%, P=0.005). The decrease in SVC and LVC with LBNP did not differ between saline and PHE trials (-13±10 vs. -17±10%, respectively, for SVC, P = 0.379). In contrast, the SVC response to HG increased from -9±12 with saline to+5±15% with PHE (P=0.002) and from -16±15 with saline to +1±16% with PHE during PECO (P=0.003). LVC responses to HG or PECO were not different from saline with PHE. Non-α-adrenergic vasoconstriction was present during LBNP. The systemic vasoconstriction during static exercise and isolated muscle metaboreflex activation, in the absence of leg vasoconstriction, was explained by an α-adrenergic mechanism. Therefore, non-α-adrenergic vasoconstriction is more emphasized during baroreflex, but not metaboreflex-mediated sympathetic activation.

Octopamine, unlike other trace amines, inhibits responses of astroglia-enriched cultures to lipopolysaccharide via a β-adrenoreceptor-mediated mechanism

Trace amines (TAs), i.e. β-phenylethylamine, tyramine and octopamine, are generally regarded as sympathomimetic compounds with structural and functional analogy with catecholamines. Previous reports have shown particularly high levels of circulating TAs in migraine and cluster headache patients. However, no clues are yet available as to the pathophysiological significance of these alterations. The effect of different TAs on the release of nitric oxide was investigated in rat astroglial cells stimulated with lipopolysaccharide (LPS). Octopamine substantially inhibited the release of NO evoked by LPS. Tyramine and β-PEA were ineffective. The inhibitory effect of octopamine was fully reverted by two selective antagonists of β-adrenergic receptors, while α-adrenergic blockade was ineffective. These data, consistent with a role of octopamine as a modulator of NO release, uncover an interaction between octopamine and β-adrenergic receptors in astroglial cells. These results may have an impact in understanding the mechanisms underlying migraine pathophysiology.

Differential effects of the antidepressant mirtazapine on amphetamine- and dizocilpine-induced PPI deficits

Prepulse inhibition (PPI) refers to the decrease in motor startle response to salient sensory stimuli (pulses) when they are closely preceded in time by another more modest sensory stimulus (prepulse). PPI deficits can be induced by stimulation of dopamine receptors (e.g., amphetamine or apomorphine) or blockade of NMDA glutamate receptors (e.g., dizocilpine or PCP). Previously we found that antagonists of α2-noradrenergic and H1-histaminergic receptors significantly attenuate PPI impairments caused by amphetamine or dizocilpine. In the current study we assessed the effects of the antidepressant mirtazapine, which has combined antagonist effects at α2-noradrenergic, H1-histaminergic and 5-HT serotonergic receptors, on amphetamine- and dizocilpine-induced PPI deficits. In Experiment 1, rats were tested for PPI of the startle response to a tactile air-puff stimulus after auditory prepulses of three different intensities. Drug treatments consisted of combinations of amphetamine (0 and 1mg/kg) and mirtazapine (0, 0.5, 1, 2, and 5mg/kg), with all rats receiving all drug doses and combinations with different counterbalanced orders. In Experiment 2, a different group of rats was tested with drug treatments consisting of combinations of dizocilpine (0 and 0.05mg/kg) and mirtazapine (0, 0.5, 1, 2, and 5mg/kg). In Experiment 1 amphetamine (1mg/kg) significantly reduced PPI whereas mirtazapine caused the opposite effect, with the highest dose of mirtazapine (5mg/kg) effectively reversing the amphetamine-induced PPI deficit. In Experiment 2 dizocilpine (0.05mg/kg) significantly reduced PPI, but mirtazapine did not have a significant effect on the inhibition of the startle response. These results indicate that the potential beneficial effects of combined α-adrenergic, 5-HT, and H1 receptor blockade in counteracting PPI deficits may be associated to cases of sensorimotor gating disorders mediated by dopamine, but not necessarily to NMDA glutamate-induced PPI impairments.

Paliperidone as an Alternative for Risperidone in a Case of Schizophrenia With Retrograde Ejaculation

Paliperidone as an Alternative for Risperidone in a Case of Schizophrenia With Retrograde Ejaculation

Pheochromocytomas, MEN 2A and Pregnancy: A Case Report with Review of the Literature

ABSTRACT Pheochromocytoma in pregnancy is a rare condition with an estimated incidence of one in 54,000 pregnancies. Pheochromocytoma in the setting of multiple endocrine neoplasia (MEN) type 2A develops in approximately 40% of the patients with this germline mutation. MEN 2A patients with pheochromocytoma are often asymptomatic compared to those with nonsyndromic pheochromocytoma. We present a 28-year-old pregnant woman with a known MEN 2A mutation who was incidentally found to have a pheochromocytoma. She underwent an uncomplicated laparoscopic right adrenalectomy after proper α- and α-adrenergic blockade. Her serum fractionated metanephrines normalized prior to discharge from the hospital. The remainder of her pregnancy was uneventful and she delivered a health baby at term. Pheochromocytoma in pregnancy requires careful management to assure the well being of both the mother and the fetus. In pregnancy, laparoscopic surgical removal of the pheochromocytoma is feasible with excellent results when performed in the second trimester. In late pregnancy, medical management with close monitoring of the mother and fetus is recommended until fetal maturity is achieved. In the third trimester, cesarean section followed by open adrenalectomy is the preferred operation. An integrated and multidisciplinary approach with close communication among the endocrinologist, surgeon and perinatal services is paramount to achieve excellent outcomes for both patients. Women with MEN 2 should be advised to refrain from pregnancy until updated biochemical and imaging studies have ruled out pheochromocytoma. How to cite this article Dy BM, Podgaetz E, Young WF, Thompson GB. Pheochromocytomas, MEN 2A and Pregnancy: A Case Report with Review of the Literature. World J Endocr Surg 2012;4(1):29-32.

Temperature-dependent sex determination modulates cardiovascular maturation in embryonic snapping turtles, Chelydra serpentina

We investigated sex differences in cardiovascular maturation in embryos of the snapping turtle Chelydra serpentina, a species with temperature-dependent sex determination. One group of eggs was incubated at 26.5°C to produce males. Another group of eggs was incubated at 26.5°C until embryos reached stage 17; eggs were then shifted to 31°C for 6 days to produce females, and returned to 26.5°C for the rest of embryogenesis. Thus, males and females were at the same temperature when autonomic tone was determined and for most of development. Cholinergic blockade increased resting blood pressure (P(m)) and heart rate (f(H)) in both sexes at 75% and 90% of incubation. However, the magnitude of the f(H) response was enhanced in males compared with females at 90% of incubation. β-adrenergic blockade increased P(m) at 75% of incubation in both sexes but had no effect at 90% of incubation. β-adrenergic blockade reduced f(H) at both time points but produced a stronger response at 90% versus 75% of incubation. We found that α-adrenergic blockade decreased P(m) in both sexes at 75% and 90% of incubation and decreased f(H) at 75% of incubation in both sexes. At 90% of incubation, f(H) decreased in females but not males. Although these data clearly demonstrate sexual dimorphism in the autonomic regulation of cardiovascular physiology in embryos, further studies are needed to test whether differences are caused by endocrine signals from gonads or by a hormone-independent temperature effect.

α-Adrenergic Blockade Unmasks a Greater Compensatory Vasodilation in Hypoperfused Contracting Muscle

We previously demonstrated that acute hypoperfusion in exercising human muscle causes an immediate increase in vascular resistance that is followed by a partial restoration (less than 100% recovery) of flow. In the current study we examined the contribution of α-adrenergic vasoconstriction in the initial changes in vascular resistance at the onset of hypoperfusion as well as in the recovery of flow over time. Nine healthy male subjects (29 ± 2) performed rhythmic forearm exercise (20% of maximum) during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included; baseline, exercise prior to inflation, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound), local (brachial artery), and systemic arterial pressure (MAP; Finometer) were measured. The trial was repeated during phentolamine infusion (α-adrenergic receptor blockade). Forearm vascular conductance (FVC; ml min−1 100 mmHg−1) and resistance (mmHg ml min−1) was calculated from BF (ml min−1) and local MAP (mmHg). Recovery of FBF and FVC (steady state inflation plus exercise value − nadir)/[steady state exercise (control) value − nadir] with phentolamine was enhanced compared with the respective control (no drug) trial (FBF = 97 ± 5% vs. 81 ± 6%, P < 0.05; FVC = 126 ± 9% vs. 91 ± 5%, P < 0.01). However, the absolute (0.05 ± 0.01 vs. 0.06 ± 0.01 mmHg ml min−1; P = 0.17) and relative (35 ± 5% vs. 31 ± 2%; P = 0.41) increase in vascular resistance at the onset of balloon inflation was not different between the α-adrenergic receptor inhibition and control (no drug) trials. Therefore, our data indicate that α-adrenergic mediated vasoconstriction restricts compensatory vasodilation during forearm exercise with hypoperfusion, but is not responsible for the initial increase in vascular resistance at the onset of hypoperfusion.

The morning blood pressure surge

The morning blood pressure surge

Ranolazine Injection Into Coronary or Femoral Arteries Exerts Marked, Transient Regional Vasodilation Without Systemic Hypotension in an Intact Porcine Model

We examined whether intracoronary or intrafemoral administration of ranolazine produces local vasodilation. Effects of intra-arterial ranolazine on coronary and femoral artery vasodilation and systemic hemodynamic function were studied in anesthetized pigs (n=27). Ranolazine, nitroglycerin, or saline (control) was injected into the left anterior descending (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment with prazosin (300 μg/kg IV) allowed determination of α(1)-adrenergic receptor involvement (n=8). Rapid intracoronary administration of ranolazine (0.048 mg/kg) to achieve high local concentrations resulted in 91±11% increase in LAD coronary artery flow and 39±7% reduction in coronary vascular resistance (both, P<0.0001). This effect lasted 2-3 minutes without change in heart rate or rate-pressure product. Mean arterial pressure decreased marginally (by 2±1 mm Hg, P=0.01). Maximum systemic plasma concentration (0.93±0.29 μmol/L) remained in subtherapeutic range. Pretreatment with prazosin abolished these effects. Intracoronary nitroglycerin (100 μg) increased LAD coronary artery flow by 112±25% (P=0.02), but the effect lasted <2 minutes; mean arterial pressure decreased by 4±1 mm Hg (P=0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie, one-tenth of the systemic bolus) resulted in a 70±19% increase in femoral artery flow (P=0.05) and 26±5% reduction in femoral artery resistance (P=0.004). At 2 minutes after the injection, the femoral flow remained 16±9% above the baseline and dilatory effects occurred without tolerance to repeated injections. Intracoronary or intrafemoral ranolazine bolus exerts a marked, 2- to 3-minute dilatory effect that is comparable to nitroglycerin in magnitude but more persistent, attributable primarily to α(1)-adrenergic blockade.

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation

The present study was designed to address the contribution of α-adrenergic modulation to the genesis of low-frequency (LF; 0.04-0.15 Hz) oscillations in R-R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; -40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α-adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low-frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low-frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high-frequency oscillations (0.15-0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP-induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α-adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α-adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Carvedilol for the Treatment of Benign Prostatic Hypertrophy in Patients With Heart Failure?

Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only β-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient's symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers.

α‐adrenergic blockade inhibits systemic vasoconstriction during handgrip exercise and muscle metaboreflex activation but not during orthostatic challenge

Orthostatic challenge increases total peripheral resistance (TPR) which is not completely explained by α-adrenergic control. It is not known whether non-α-adrenergic mechanisms are involved during exercise. Twelve healthy subjects underwent lower-body negative pressure LBNP (5 min, −40 mmHg) and static handgrip exercise HG (5 min, 20% of MVC) followed by post-exercise circulatory occlusion (PECO, 5 min) with and without α-adrenergic blockade by phentolamine (PHE). Aortic blood flow and finger blood pressure were measured to calculate cardiac output (Q) and TPR during the last minute of each intervention. LBNP resulted in a greater reduction in Q with PHE than without PHE (p<0.05). Response in Q was larger during HG and PECO with PHE than without PHE (p<0.05, for both). TPR increased similarly during LBNP with and without PHE (+6.2±5.3 vs. +3.6±3.3 L/min/mmHg, p=0.110). In contrast, PHE abolished the increases in TPR during HG (+3.1±4.0 vs. −0.8±3.4 L/min/mmHg, p<0.001) and PECO (+6.5±7.9 vs. +0.3±3.9 L/min/mmHg, p=0.005). These data suggest that while α-adrenergic control is not responsible for increasing TPR during LBNP, α-adrenergic inhibition blunts the responses in TPR during prolonged 5-min model of static handgrip exercise and muscle metaboreflex activation. Supported by Academy of Finland, TEKES Finland, Canadian Institutes of Health Research and Finnish Foundation of Cardiovascular Research

Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo

AMP-activated protein kinase (AMPK), an evolutionarily conserved serine-threonine kinase that senses cellular energy status, is activated by stress and neurohumoral stimuli. We investigated the mechanisms by which adrenergic signaling alters AMPK activation in vivo. Brown adipose tissue (BAT) is highly enriched in sympathetic innervation, which is critical for regulation of energy homeostasis. We performed unilateral denervation of BAT in wild type (WT) mice to abolish neural input. Six days post-denervation, UCP-1 protein levels and AMPK α2 protein and activity were reduced by 45%. In β(1,2,3)-adrenergic receptor knock-out mice, unilateral denervation led to a 25-45% decrease in AMPK activity, protein expression, and Thr(172) phosphorylation. In contrast, acute α- or β-adrenergic blockade in WT mice resulted in increased AMPK α Thr(172) phosphorylation and AMPK α1 and α2 activity in BAT. But short term blockade of α-adrenergic signaling in β(1,2,3)-adrenergic receptor knock-out mice resulted in decreased AMPK activity in BAT, which strongly correlated with enhanced phosphorylation of AMPK on Ser(485/491), a site associated with inhibition of AMPK activity. Both PKA and AKT inhibitors attenuated AMPK Ser(485/491) phosphorylation resulting from α-adrenergic blockade and prevented decreases in AMPK activity. In vitro mechanistic studies in BAT explants showed that the effects of α-adrenergic blockade appeared to be secondary to inhibition of oxygen consumption. In conclusion, adrenergic pathways regulate AMPK activity in vivo acutely via alterations in Thr(172) phosphorylation and chronically through changes in the α catalytic subunit protein levels. Furthermore, AMPK α Ser(485/491) phosphorylation may be a novel mechanism to inhibit AMPK activity in vivo and alter its biological effects.

The curse of the sympathetic nervous system: are men or women more unfortunate?

The curse of the sympathetic nervous system: are men or women more unfortunate?

No effect of systemic isocapnic hypoxia on α-adrenergic vasoconstrictor responsiveness in human skin

Hypoxia impairs body temperature regulation and abolishes the decline in skin temperature associated with cold exposure, suggesting that cutaneous vasoconstriction is impaired. The purpose of this study was to test the hypothesis that cutaneous vasoconstriction to intradermal tyramine, an index of post-junctional vasoconstrictor responsiveness, is reduced during hypoxia. Twelve subjects (six males, six females) had three microdialysis fibres placed in the ventral forearm. Fibres received either lactated ringers, 5 mm yohimbine (α-adrenergic blockade), or 10.5 μm BIBP-3226 (to antagonize neuropeptide Y Y(1) receptors). Skin blood flow was assessed at each site (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled to baseline. Vasoconstrictor responses to tyramine (173 μm) were tested during normoxia and steady-state isocapnic hypoxia (SaO(2) = 80%) in random order. During normoxia, tyramine reduced CVC by 56.0±5.6 and 50.3±8.0% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.445 between sites) whereas CVC in the yohimbine site did not change (P=0.398 vs. pre-tyramine). During isocapnic hypoxia, tyramine reduced CVC by 55.9±5.1 and 54.2±5.4% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.814 between sites) whereas CVC was unchanged in the yohimbine site (P=0.732 vs. pre-tyramine). Isocapnic hypoxia did not affect vasoconstrictor responses at any site (all P>0.05 vs. normoxia). We conclude that post-junctional α-adrenergic vasoconstrictor responsiveness is not affected by hypoxia in non-acral skin.

Detecting activation of the sympatho-adrenal axis from haemodynamic recordings, in conscious rabbits exposed to acute stress

When assessing sympathetic activation in acute stress, the attention is often limited to the sympatho-neural axis, whereas sympatho-adrenal activation, that can only be detected with poor time resolution from the concentration of plasma catecholamines, is often neglected. This study is aimed at re-investigating the role and the relevance of the sympatho-adrenal system in acute stress based on the analysis of haemodynamic responses in conscious rabbits. Experiments were carried out on 19 rabbits implanted with chronic probes for arterial blood pressure and for blood flow in the facial artery. Cardiovascular responses to a randomized sequence of acute stressors (pinprick, air jet, oscillation of the cage, inhalation of formaldehyde vapours and im injection of hypertonic saline) were recorded before and after α-adrenergic blockade (phentolamine) and unilateral section of the cervical sympathetic trunk (decentralization). Plasma catecholamine concentrations were analysed in four animals. All stressors induced an increase in arterial blood pressure and a reduction of vascular conductance in the facial artery ranging on average from 24% (pinprick) to 55% (box oscillation). Such vasoconstrictor response was abolished by phentolamine. In decentralized arteries, the vasoconstriction was delayed by 10-15 s and decreased in magnitude in a stressor-dependent way, indicating an adrenaline-mediated effect in the late phase of the stress response that was confirmed by changes in plasma adrenaline concentration. In conscious rabbits, rapid release of adrenaline makes a prominent contribution to vasoconstriction in response to different stressors including box oscillation, muscle pain and air jet but not the nasopharyngeal stimulation.

Morning Surge in Blood Pressure and Cardiovascular Risk

Hypertension is the most powerful risk factor for the cardiovascular diseases, including stroke, coronary artery disease, heart failure, chronic kidney disease, and aortic and peripheral arterial diseases. There is a significant variability in BP level among hypertensives; however, the diagnosis of hypertension and the therapeutic target of BP are based on the average of each BP measured. There is marked diurnal variation in the onset time of cardiovascular events, with the peak being exhibited in early morning. Blood pressure (BP) also exhibits a similar diurnal variation, with a decrease during sleep and a surge in the morning.1,2 In addition to the persistent pressor stress (averaged throughout a 24-hour period), dynamic diurnal variation in pressor stress from the nadir to the peak in the morning, that is, the morning surge in BP, would be expected to progress target organ damage and trigger cardiovascular events, particularly those occurring in the morning.3,4 Because my group first demonstrated that exaggerated morning surge in BP constitutes a risk for stroke independent of 24-hour BP,5 there has been a steady increase in cross-sectional and prospective evidence supporting the idea that morning BP surge is an independent risk factor for cardiovascular disease. Here I review the recent evidence and the remaining unresolved issues on this topic. ### Prospective Findings on Cardiovascular Events Normal morning BP surge is a physiological phenomenon, but an exaggerated morning BP surge is a cardiovascular risk. Thus, the association between the degree of morning BP surge and cardiovascular risk is not linear but rather has a threshold. There have been 6 prospective studies demonstrating that the morning surge in BP is a risk for cardiovascular events (Table 1).5–10 These studies have used 3 different definitions of the morning BP surge as follows (Figure 1): (1) a sleep-trough surge defined as the morning BP (2-hour …

Alpha‐receptor blockade improves muscle perfusion and glucose uptake in heart failure

Alpha-adrenergic receptor-mediated vasoconstriction might underlie the insulin resistance seen in conditions associated with increased sympathetic tone, like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake (FGU) in CHF patients. In 8 CHF patients and in 12 healthy volunteers, FBF (plethysmography) and FGU were measured in both forearms during a 150 min hyperinsulinaemic euglycaemic clamp procedure. During the final 30 min of the clamp, phentolamine was infused into one arm (experimental arm) at a dose of 5.0 μg; min(-1) dL(-1) of forearm volume. Insulin infusion (t = 0-120 min) increased FGU in the two groups, without affecting FBF. In the CHF group, α-adrenergic receptor blockade by phentolamine (t = 120-150 min) further increased FGU in the experimental arm from 3.0 ± 0.7 to 5.0 ± 0.9 μmol min(-1) dL(-1) (P = 0.03). Forearm glucose uptake in the contralateral forearm remained unchanged. In the control group, phentolamine infusion did not increase FGU in the experimental forearm. The increase in blood flow in response to phentolamine was similar in both groups (CHF: 2.1 ± 0.3-7.5 ± 1.7 mL min(-1) dL(-1), P < 0.001; controls 1.5 ± 0.2-5.5 ± 0.8 mL min(-1) dL(-1), P < 0.001 for both, CHF vs. control, P = 0.2). Phentolamine did not affect FBF in the control arm in either group. Alpha-adrenergic receptor blockade improves FGU in CHF patients. As the increase in FBF is similar in controls and CHF patients, this might be explained by an improved glucose-extraction capacity in CHF patients.

Priapism During Treatment With Olanzapine, Quetiapine, and Risperidone in a Patient With Schizophrenia

Priapism During Treatment With Olanzapine, Quetiapine, and Risperidone in a Patient With Schizophrenia