Alpha-adrenergic Receptor Blocker Research Articles

Activation-dependent regulation of galanin gene expression in gonadotropin-releasing hormone neurons in the female rat.

In rats, galanin is colocalized in GnRH neurons, and galanin mRNA in GnRH neurons is increased coincidentally with the preovulatory gonadotropin surge. Whether the induction of galanin mRNA in GnRH neurons at proestrus reflects the action of sex steroids is unknown. We tested this hypothesis by challenging ovariectomized rats (n = 7) with estrogen and progesterone (E/P) to induce a LH surge and measuring galanin mRNA in GnRH neurons to determine whether there was an associated induction of galanin message in these cells. We used single and double label in situ hybridization and image analysis to compare among groups the levels of both galanin mRNA and GnRH mRNA in GnRH neurons. We found that steroid-primed animals showed an approximately 400% induction of galanin mRNA signal in GnRH neurons over that in vehicle-treated animals. Second, we hypothesized that steroid-dependent events which induce the expression of galanin mRNA in GnRH neurons depend on transsynaptic input to GnRH neurons. We tested this hypothesis by examining the effect of a pharmacological blockade of the steroid-induced activation of GnRH neurons on levels of galanin mRNA in these cells. We killed groups of ovariectomized adult female rats at the peak of a E/P-primed LH surge (n = 7) and after steroid priming followed by blockade of the LH surge with either the general anesthetic pentobarbital (n = 7) or the specific alpha-adrenergic receptor blocker phenoxybenzamine (n = 7). When we examined signal levels representing galanin mRNA content in GnRH neurons, we observed a 4-fold increase in signal for galanin mRNA in the GnRH neurons of steroid-primed (E/P surge) animals compared with that in oil-treated controls (P < 0.0004). This increase in galanin mRNA was prevented when the LH surge was blocked by treatment with either pentobarbital or phenoxybenzamine (P < 0.03 and P < 0.0001 vs. E/P surge controls, respectively). Cellular levels of GnRH mRNA were not different among control, E/P, and E/P plus pentobarbital groups (P > 0.2). These observations suggest that an increase in galanin mRNA levels in GnRH neurons is tightly coupled to the occurrence of a LH surge. By inference, induction of galanin mRNA in GnRH neurons reflects their activation, possibly via afferent neurons that transduce the steroid signal to GnRH neurons.

Vasoactive Intestinal Peptide: Electrophysiologic Activity in the Newborn Heart

We performed intracardiac electrophysiologic studies of the effects of vasoactive intestinal peptide (VIP, 0.125 micrograms/kg/min) on sinus and atrioventricular (AV) nodal function, intracardiac conduction, and myocardial refractoriness in two groups of neonatal dogs (aged 6-16 d). Group I consisted of eight neonates in whom VIP was administered after bilateral vagotomy and beta-blockade with propranolol. Group II consisted of five neonates studied after vagotomy and propranolol, plus total chemical sympathectomy (6-hydroxydopamine). In both groups, VIP resulted in a significant shortening of sinus cycle length. AV nodal conduction time, measured as the AH interval (the time from the onset of the atrial electrogram to the onset of the His bundle electrogram in the His electrode catheter) during atrial pacing, also shortened after VIP. His-Purkinje conduction time and atrial effective refractory periods were unchanged by VIP. In other experiments, the direct chronotropic effect of VIP was evaluated in five isolated neonatal canine hearts using a modified Langendorff technique. In these hearts, the spontaneous cycle length decreased from 403 +/- 88 to 293 +/- 69 ms, or -28 +/- 4% (mean +/- SD), after exposure to 0.1-0.5 nmol of VIP (p < 0.001). In nine other newborns (aged 4-16 days), the effect of selective alpha 1- and alpha 2-adrenergic receptor blockade on the positive chronotropic effect of VIP was evaluated. The effect of VIP on sinus cycle length was not altered by the alpha 1-adrenergic receptor blocker prazosin or by the alpha 2-adrenergic receptor blocker yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia.

1. Peripheral nerve injury sometimes leads to the development of neuropathic pain. One of the symptoms of such neuropathic pain is mechanical allodynia, pain in response to normally innocuous mechanical stimuli. We hypothesized that sympathetically driven dysfunction of cutaneous mechanoreceptors is responsible for signaling mechanical allodynia. The present study was undertaken to identify the types of sensory receptors that potentially mediate mechanical allodynia, with the use of a rat neuropathic pain model we have developed. 2. One week to 10 days after tight ligations of the L5 and L6 spinal nerves on one side, the rats fully developed behavioral signs of mechanical allodynia on the affected hindlimb. Various cutaneous mechanoreceptors originating from the neuropathic foot were examined by single-fiber recordings from the L4 dorsal root. 3. Although no particular abnormalities were found in other types of cutaneous mechanoreceptors, an unusual type of mechanoreceptor was found to be innervating the neuropathic foot. The response characteristics of this type of receptor resemble those of rapidly adapting mechanoreceptors (RAs), but with low and irregular static discharges during a maintained mechanical stimulus. We termed this unusual type as a "modified rapidly adapting" mechanoreceptor (MRA). 4. The response characteristics of MRAs change to those of typical RAs after a systemic injection of phentolamine, an alpha-adrenergic receptor blocker. 5. We conclude that many RAs become abnormal under the influence of sympathetic efferents in neuropathic pain, so that their response patterns change to those of MRAs. We propose that this abnormality is responsible for signaling the mechanical allodynia that can be seen in neuropathic pain states such as causalgia.

NPY is not a primary mediator of the acute thyroid blood flow response to sympathetic nerve stimulation

It has been suggested that thyroid blood flow is regulated by both sympathetic and parasympathetic nerves. The purpose of our experiments was to study the role of neuropeptide Y (NPY) in the sympathetic neural control of thyroid blood flow. Sympathetic nerve fibers to the thyroid contain both norepinephrine (NE) and NPY. Therefore, NE (15 nmol iv bolus) and NPY (12 or 1.7 nmol/kg body wt iv infusion; 4 min) were administered to anesthetized male rats (250-300 g) either alone or together, with or without an alpha-adrenergic receptor blocker (phentolamine; 10 mg/kg body wt iv bolus). Experiments were also performed in which the cervical sympathetic trunks were stimulated (30 Hz, 10 V; 0.5 ms; 2 min) with or without phentolamine. Thyroid blood flow was monitored continuously by laser-Doppler blood flowmetry. Results are expressed as thyroid vascular conductance (TVC). NE or NPY at both doses decreased TVC relative to that in control saline-infused rats (P < 0.05). No potentiation of the NE effect by NPY was observed when the first dose of NE was injected 2 min after a high or low dose of NPY. However, the effect of a second dose of NE, injected 15 min after the end of the low dose of NPY, was prolonged compared with the effect of a second dose of NE in saline-infused rats. Phentolamine blocked the effect of NE but not that of NPY. Stimulation of the cervical sympathetic trunks decreased TVC (P < 0.01 vs. sham), and this effect was completely blocked by phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary calcium modulates blood pressure through alpha 1-adrenergic receptors.

To investigate the role of adrenergic receptor activity in dietary calcium-induced alterations in blood pressure, weanling spontaneously hypertensive rats (SHR) were placed on either high-calcium (2.0%) or low-calcium (0.1%) diets for 1-2 wk. Baseline blood pressure was higher and pressor responses to exogenous norepinephrine (NE) were greater in the SHR on low-calcium diets than high-calcium diets. There was no difference between diet groups in circulating NE or in the pressor response to angiotensin II. The difference in basal blood pressure was eliminated by the alpha 1-adrenergic receptor blockers phentolamine and prazosin but was not altered by alpha 2-, beta 1-, or beta 2-adrenergic receptor blockade (idazoxan, metoprolol, and butoxamine, respectively). Furthermore, hypotension produced by either calcitonin gene-related peptide, captopril, or nitroprusside failed to eliminate the diet-induced difference in blood pressure. The results suggest the possibility that diet-induced differences in alpha 1-adrenergic activity may be responsible, in part, for variations in blood pressure on different calcium diets.

Involvement of alpha- and beta-adrenergic receptors in the regulation of rat pineal N-acetyltransferase activity during development.

The regulation by alpha- and beta-adrenergic receptor agonists of rat pineal N-acetyltransferase (NAT) activity during development was studied. We found that isoproterenol, a beta-adrenergic agonist, exhibited a weak stimulatory effect on pineal NAT activity during the first 3 weeks of age. Indeed, the drug did not mimic the effect of darkness on pineal NAT activity until the fourth week of age. The results might be explained by the existence of other mechanisms, in addition to those that involve beta-adrenergic receptors, which regulate pineal NAT activity during early postnatal development. In line with this, we determined that phenylephrine, an alpha 1-adrenergic agonist, stimulated NAT activity during both the day and at night in 2-week-old rats, while exhibiting no effect in adult rats. Methoxamine, an alpha 1-adrenergic agonist more selective than phenylephrine, also activated NAT activity in young, but not in adult, rats. Moreover, prazosin, a selective alpha 1-adrenergic receptor blocker, prevented pineal NAT activation by norepinephrine or darkness at night in 2-week-old rats, but not in adult animals. The results suggest that alpha 1-adrenergic receptors may be more important than beta-adrenergic receptors in regulating rat pineal NAT activity during development.

Involvement of alpha- and beta-adrenergic receptors in the regulation of rat pineal N-acetyltransferase activity during development

The regulation by alpha- and beta-adrenergic receptor agonists of rat pineal N-acetyltransferase (NAT) activity during development was studied. We found that isoproterenol, a beta-adrenergic agonist, exhibited a weak stimulatory effect on pineal NAT activity during the first 3 weeks of age. Indeed, the drug did not mimic the effect of darkness on pineal NAT activity until the fourth week of age. The results might be explained by the existence of other mechanisms, in addition to those that involve beta-adrenergic receptors, which regulate pineal NAT activity during early postnatal development. In line with this, we determined that phenylephrine, an alpha 1-adrenergic agonist, stimulated NAT activity during both the day and at night in 2-week-old rats, while exhibiting no effect in adult rats. Methoxamine, an alpha 1-adrenergic agonist more selective than phenylephrine, also activated NAT activity in young, but not in adult, rats. Moreover, prazosin, a selective alpha 1-adrenergic receptor blocker, prevented pineal NAT activation by norepinephrine or darkness at night in 2-week-old rats, but not in adult animals. The results suggest that alpha 1-adrenergic receptors may be more important than beta-adrenergic receptors in regulating rat pineal NAT activity during development.

Epinephrine induces beta-adrenergic desensitization and differentiation of HL-60 cells.

The HL-60 cell line was cultured in a serum-free medium and exposed to various concentrations of EPI. The effects on cell growth, differentiation and beta-adrenergic response were followed during the culture period of 72 h. Short-term exposure (3 min) to EPI (1 nM-1 mM) in the presence of theophylline (4 mM) caused a dose-dependent increase of cAMP levels with a maximum of 1500% above basal levels. When the cells were exposed to EPI (1 nM-10 microM) for 72 h, a dose-dependent increase of cAMP levels with a maximum of 60% above basal levels. Sustained exposure to EPI generated a dose-dependent desensitization of the beta-adrenergic signal system. After EPI treatment for 72 h, IPR (10 microM for 3 min) in the presence of theophylline (4 mM) increased cAMP-levels by only 80% above baseline level (cAMP levels after maintained exposure to EPI), compared to 1080% above unstimulated level in control cells. The alpha-adrenergic receptor blocker PHENT (10 microM) did not affect baseline cAMP level or IPR-dependent cAMP response, but a mixture of EPI and PHENT increased the response to IPR. The HL-60 cell growth was not influenced by EPI. However, after repeated exposure to EPI for 72 h a concentration-dependent increase of HL-60 differentiation was demonstrated. Differentiation was not influenced by PHENT. These results suggest a differentiation induction due to a beta-adrenergic-induced cAMP elevation.

Endothelial role in ouabain-induced contractions in guinea pig carotid arteries.

The influence of endothelium on the direct contractile effects of ouabain in vascular smooth muscle was analyzed in isolated perfused guinea pig carotid arteries. After blocking the neurogenic component of the glycoside contraction with alpha-adrenergic receptor blocking drugs or treating the animals with reserpine, ouabain-induced contractions were markedly reduced in vessels with intact endothelium. However, removal of the vascular endothelium from reserpinized carotid arteries resulted in ouabain-induced contractions similar to those observed in control arteries. These effects were not mimicked by the inhibitor of nitric oxide NG-monomethyl L-arginine or by the cyclooxygenase blocker indomethacin. Bioassay experiments suggested that these endothelial effects are mediated by diffusible factors. Uptake of 86Rb to measure sodium pump activity was significantly reduced by removal of the endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of contractions induced by ouabain, likely mediated by a diffusible factor (or factors) released from these cells. The nature of this substance is unknown, but it is neither related to prostaglandins nor a nitric oxide-related compound. Its mechanism of action could be the stimulation of vascular sodium pump activity, the antagonism of the pump's inhibition by ouabain, or both.

Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze.

Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors. As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.

Hormones increase oxygen uptake in periportal and pericentral regions of the liver lobule.

The effect of several hormones known to alter intracellular free Ca2+ on rates of O2 uptake in periportal and pericentral regions of the liver lobule was studied in the perfused liver. Regional O2 uptake was measured by stopping the flow and monitoring the decrease in O2 concentration. When perfusion was in the anterograde direction, basal rates of O2 uptake were two to three times higher in periportal than in pericentral regions, and phosphorylase alpha activity, which increases as a function of intracellular free Ca2+ levels, was higher in periportal regions. In contrast, when perfusion was in the retrograde direction, rates of O2 uptake were two to three times greater in pericentral regions. Infusion of epinephrine (0.1 microM) or angiotensin II (5 nM) increased the rate of O2 uptake nearly exclusively in downstream areas of the lobule where O2 tension was low. When perfusions were in the anterograde direction, epinephrine increased phosphorylase alpha activity significantly only in pericentral regions. Stimulation of O2 uptake by epinephrine was blocked by the alpha-adrenergic receptor blocker phentolamine (1 microM) but not by the beta-receptor blocker propranolol. Thus hormones that increase intracellular calcium stimulate O2 uptake predominantly in regions of the liver lobule where O2 tension is lowest, supporting the hypothesis that oxygen tension regulates O2 uptake in the liver via mechanisms involving intracellular free Ca2+.

Changes in phosphoinositide-specific phospholipase C and phospholipase A2 activity in ischemic and reperfused rat heart.

Phospholipid metabolism is altered during ischemia and post-ischemic reperfusion. Past studies demonstrating elevated myocardial free fatty acid and lysophospholipid content infer accelerated phospholipid degradation involving phospholipase A activity. Recently, ischemic and post-ischemic reperfusion (reperfusion) have been shown to affect levels of phosphoinositide (PPI) degradation products. Considering the role of PPI turnover in regulation of cellular calcium homeostasis, our laboratory and others have suggested that alteration in the metabolism of the inositol phospholipids could play a role in the development of ischemia-induced calcium overload injury. Using an isolated rat heart model (Langendorff perfusion), this study examines the effect of global ischemia and reperfusion on ventricular phosphoinositide-specific phospholipase C (PLC) activity and PLA2 activity. The primary purpose was to determine if ischemia and reperfusion-induced changes in PLC activity could explain previously observed changes in PPI degradation products, and whether PLC and PLA2 activities were similarly or differentially altered by ischemia and reperfusion. PLC and PLA2 activities were measured in cytosolic and total membrane fractions from control (perfused), ischemic (5, 10, 30, and 60 min), and post-ischemic reperfused ventricular tissue. Phospholipase activity was determined under optimal in vitro conditions using exogenous radiolabeled substrates. Alterations in membrane-associated PPI-PLC activity correlated with reported ischemia and reperfusion-induced changes in ventricular content of PPI metabolites. Membrane PLC activity increased slightly at 5 min of ischemia, decreased significantly at 10 min of ischemia, and continued to decrease with longer duration of ischemia (73% of control after 60 min). Cytosolic PPI-PLC activity was decreased at 5 min, and then significantly increased by longer durations of ischemia, while cytosolic PLA2 activity was reduced at all time points. Pretreatment with muscarinic, alpha 1-adrenergic, beta-adrenergic, and adenosine receptor blockers did not alter ischemia-elicited changes in PLC activity. Reperfusion caused a 140% to 200% rise in the activities of all phospholipases in all fractions after 40 min of ischemia, but not after 10 min of ischemia. Results suggest 1) ischemia and reperfusion-elicited alterations in membrane-associated PPI-PLC activity can explain previously observed changes in phosphoinositide turnover metabolites, 2) cytosolic and membrane-associated PPI-PLC and PLA2 activities are not uniformly affected by ischemia, 3) reperfusion following ischemia of sufficient duration initiates uniform activation of PIP2-PLC and PLA2, and 4) because ischemia and reperfusion-induced changes in phospholipase activity can be detected under optimal in vitro assay conditions (removed from the in vivo ischemic microenvironment), it is likely that the enzymes themselves have been altered.

Acute and chronic hemodynamic effects of drugs with different actions on adrenergic receptors: A comparison between alpha blockers and different types of beta blockers with and without vasodilating effect

The regulation of vascular resistance, cardiac output, and thus blood pressure can be influenced by antihypertensive drugs acting at central and peripheral adrenergic receptors. The results presented here are from acute or chronic studies in 205 patients with mild or moderately severe essential hypertension: beta blockers (N = 101); alpha blockers (N = 36); a separate alpha- + beta-blocker combination or the combination agent labetalol (N = 37); prizidilol, a beta-blocker/vasodilator (N = 14); and dilevalol, a beta blocker/beta 2-stimulator (N = 17). Beta blockers without strong intrinsic sympathomimetic activity reduce heart rate and cardiac output immediately, but due to a reflex increase in total peripheral resistance index, blood pressure is unchanged or only slightly reduced. During chronic use, total peripheral resistance drops towards pretreatment level and pressure falls. Beta blockers with strong intrinsic sympathomimetic activity do not reduce heart rate or cardiac output at rest when sympathetic tone is low. During exercise, heart rate and cardiac output are reduced, but less than with conventional beta blockers, and resistance is unchanged or slightly reduced. An acute and chronic reduction in blood pressure can be produced by alpha-adrenergic receptor blockers (prazosin, doxazosin, trimazosin), and in these cases the fall occurs via a reduction in total peripheral resistance index without reflex tachycardia. These drugs tend to increase exercise stroke volume and cardiac output during chronic treatment. Free combinations of beta and alpha blockers or the use of the fixed combination drug, labetalol, induce marked reductions in blood pressure at rest and during exercise, mainly through a reduction in total peripheral resistance index. During chronic treatment, exercise stroke volume and cardiac output are well maintained. In acute studies with dilevalol, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were reduced (p less than 0.001) within 1 hour in 17 males with essential hypertension (WHO stage I) who received 200-400 mg oral dilevalol. The reduction in MAP was around 16-17% and was associated with an immediate fall in the total peripheral resistance index of the same magnitude (14%, p less than 0.001) after 1 hour at rest. There were no significant changes in heart rate or cardiac index.(ABSTRACT TRUNCATED AT 400 WORDS)

β and αAdrenergic Mechanisms Are Involved in Regulation of Rat Pineal Type II Thyroxine 5'- Deiodinase Activity during Development*

Adrenergic regulation of type II T4 5'-deiodinase (5'-D) activity has been studied in the rat pineal gland during development. Nocturnal increases in 5'-D activity gradually rose from the second week of age until the sixth week. Isoproterenol, a beta-adrenergic agonist, stimulated 5'-D activity during the daytime; however, the pattern of stimulation during development was slightly different from nocturnal activation of the enzyme, since pineal 5'-D activity could be clearly activated by isoproterenol from the first week of age. Isoproterenol activation of the enzyme always reached more than 70% of nocturnal values at all ages studied. Phenylephrine, an alpha-adrenergic agonist, did not increase the enzyme activity. Another selective alpha-adrenergic agonist, methoxamine, as well as clonidine, an alpha 2-adrenergic agonist, were ineffective in stimulating the enzyme, while norepinephrine or terbutaline, a beta-adrenergic agonist, clearly activated it. Additional results showing a role for alpha-adrenergic receptors on pineal 5-D activity were obtained when alpha- and beta-adrenergic receptor blockers were used. Thus, propranolol, a beta-adrenergic blocker, clearly prevented pineal 5'-D activation in both 2- and 6-week-old rats when the gland was stimulated by either norepinephrine or darkness at night. However, prazosin, a selective alpha 1-adrenergic receptor blocker, also prevented the norepinephrine-induced or darkness-induced activation of the enzyme in 2-week-old rats, although it was ineffective when used in 6-week-old rats. Moreover, at night and after 3 h of exposure to darkness, phenylephrine was able to activate the enzyme. Results strongly suggest a role for alpha-adrenergic receptors, in addition to beta-adrenergic receptors, in regulating rat pineal 5'-D activity during development.

Alpha‐adrenergic blockers: Mechanism of action, blood pressure control, and effects on lipoprotein metabolism

The sympathetic nervous system plays a major role in the pathogenesis of essential hypertension and is mediated by the alpha and beta receptors. The alpha receptor is divided into two types, alpha 1 and alpha 2, based on response to epinephrine and norepinephrine. alpha 1-Adrenergic receptors have a high affinity for drugs such as prazosin, doxazosin, and terazosin, which act to reduce blood pressure by selective blockade of the receptor. These agents provide a rational approach to the treatment of hypertension by correcting elevated total peripheral resistance, the fundamental hemodynamic abnormality in essential hypertension. In contrast, early alpha-adrenergic receptor blockers nonselectively blocked both alpha 1 and alpha 2 receptors and were unsuitable as antihypertensive agents because they induced tachycardia and patients developed a tolerance to them rapidly. alpha 1-Adrenergic blockers also have beneficial effects on plasma lipoproteins, tending to decrease levels of triglycerides and cholesterol and increase levels of high-density lipoprotein (HDL) cholesterol and the HDL cholesterol/total cholesterol ratio. beta-Adrenergic blockers, such as propranolol and atenolol, have been shown to have an adverse effect on the lipid profile by tending to increase levels of triglycerides and decrease HDL cholesterol. A number of mechanisms contribute to these effects, in particular, adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate. Doxazosin has been shown to increase the activity of LDL receptors, which may be partly responsible for its beneficial effect on plasma lipids and lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vivo Stimulation of Rat Pineal Type II Thyroxine 5'-Deiodinase Activity by Either Norepinephrine or Isoproterenol

Herein we show, for the first time, a very marked increase in thyroxine 5'-deiodinase (5'-D) activity in rats injected with norepinephrine (NE) and desmethylimipramine, a drug which inhibits NE uptake by nerve terminals. The response to NE was greater in pineals collected from hypothyroid animals than in glands from euthyroid animals. NE was more effective in stimulating pineal 5'-D than was isoproterenol, suggesting that, in addition to beta-adrenergic receptors, alpha-adrenergic receptors might be involved in the 5'-D activation. However, phenylephrine, an alpha-adrenergic agonist, did not potentiate the effect of isoproterenol on pineal 5'-D activity. The nocturnal increase in pineal 5'-D activity was completely abolished by propranolol, a beta-adrenergic receptor blocker, while prazosin, an alpha-adrenergic receptor blocker, had minimal effect. These results show that the role of alpha-receptors in promoting the NE-mediated rise in rat pineal 5'-D activity is minor in contrast to the role of beta-adrenergic receptors.

Do the known specific alpha-1 adrenergic receptor blockers act as antipyretics?

Do the known specific alpha-1 adrenergic receptor blockers act as antipyretics?

Peptide-amine interactions in the hypothalamic paraventricular nucleus: analysis of galanin and neuropeptide Y in relation to feeding

The neuropeptide galanin (GAL) has been found to elicit feeding after injection into the paraventricular hypothalamic nucleus (PVN), where it coexists with norepinephrine (NE), a neurotransmitter believed to be important in the control of natural feeding behavior. Using pharmacological tools, this study investigated the possibility that PVN GAL influences food intake via its direct interaction with the noradrenergic system localized in this nucleus. Tests with alpha-adrenergic receptor blockers demonstrated that GAL-induced feeding, similar to NE-stimulated feeding, depends specifically upon functional alpha 2-receptor sites. Further, experimentation with the catecholamine synthesis inhibitors, alpha-methyl-p-tyrosine and Fla-63, suggested that GAL's action also depends upon the release of endogenous NE. This is in contrast to another hypothalamic peptide, neuropeptide Y, which is also a strong stimulant of food intake and coexists with NE in the PVN. Neuropeptide Y remains effective in eliciting feeding in the presence of alpha 2-receptor antagonists and catecholamine-synthesis inhibitors, suggesting that, unlike GAL, it can act independently of endogenous NE.

Cost-effectiveness of antihypertensive treatment. General considerations.

Cost-effectiveness analysis, a set of methods for estimating the costs and health effects of medical interventions, helps decision makers to compare alternative treatments and to decide which interventions are appropriate in which situations. This article outlines some fundamental principles of cost-effectiveness analysis and discusses the characteristics necessary if alternative therapies are to be more cost-effective than traditional drug treatment for hypertension. The discussion focuses primarily on the newer drugs like angiotensin converting enzyme inhibitors, alpha-adrenergic receptor blockers, and calcium antagonists.

Choosing initial therapy for hypertension. A personal view.

With numerous safe and effective antihypertensive drugs now available, the clinician should no longer choose only diuretic agents or beta-adrenergic receptor blockers (beta-blockers) as initial therapy. Five classes of agents, including angiotensin converting enzyme inhibitors, beta-blockers, calcium entry blockers, peripheral alpha 1-adrenergic receptor blockers, and thiazide diuretic agents, are all appropriate monotherapy in properly selected patients. The choice depends on efficacy, side effects, demography, comorbidity, dosage schedule, cost, mechanism of drug action, and the pathophysiology of the patient's hypertension. Extensive data are now available that will assist the clinician in choosing an agent that has the greatest probability of success without the need for extensive biochemical or hemodynamic evaluation.