Search PubMed⌕ Search

Biomedical subjects

G Tsujimoto

Publications and source records attributed to G Tsujimoto.

At least 19 recordsLinked to original sources
PubMed1992

[Molecular structure and function of renal adrenergic receptors].

The kidney is the principal organ in the body that mediates the excretion of water and minerals, and also functions as an endocrine organ in producing hormones, enzymes (e.g., renin), and vasoactive molecules (e.g., prostaglandins). Circulating catecholamines and autonomic innervation of the kidney can influence those important functional responses as well as vascular constriction via renal adrenergic receptors. The adrenergic receptors are members of a large family of G protein-coupled receptors. Recent advance of molecular cloning has revealed a growing heterogeneity of adrenergic receptor subtypes. They share a common topographical motif consisting of seven putative transmembrane regions, where. They are thought to be essential for ligand binding. Multiple subtypes of adrenergic receptors may exist in the kidney. Defining the precise role of renal adrenergic receptors in disease states, particularly hypertension, will certainly require the application of new tools of biochemistry and molecular biology.

Glomerular Filtration Rate↗
PubMed1990

Different desensitization mechanisms of two alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta.

Using alpha 1-adrenoceptor selective antagonists chlorethylclonidine (CEC) and WB4101, both functional and radioligand binding studies showed that rabbit aorta contains at least two pharmacologically distinct alpha 1-adrenoceptor subtypes of approximately 10% alpha 1a and 90% alpha 1b receptors, and that each receptor subtype has a distinct role in the alpha 1-adrenoceptor-mediated vasoconstrictive response through different biochemical mechanisms for increasing intracellular Ca2+; alpha 1a receptors cause tonic response predominantly dependent on the influx of extracellular Ca2+, while alpha 1b receptors stimulate phosphoinositides (PI) hydrolysis/intracellular Ca2+ mobilization and cause phasic response mainly independent of extracellular Ca2+. Incubation of rabbit aorta with 10 microM noradrenaline (NA) for 2 h resulted in a reduction in the phasic response and PI hydrolysis to NA with no change in the tonic response. Similar to the NA incubation, the protein kinase C stimulator PMA (1 microM) selectively attenuated alpha 1b-receptor mediated PI hydrolysis and phasic contraction but had little effect on alpha 1a-receptor-mediated tonic response. The protein kinase C inhibitor H-7 (10 microM) blocked these inhibitory effects of PMA. Treatment with H-7 (10 microM) prevented the NA-induced alpha 1b receptor desensitization in inositol monophosphate (IP) formation and phasic response. The results suggest that activation of C kinase may be involved in the development of selective desensitization of alpha 1b receptors by a short-time in vitro incubation of NA.

Adrenergic alpha-Antagonists↗
PubMed1990

Characterization of alpha 1-adrenergic receptor subtypes linked to iodide efflux in rat FRTL cells.

We have characterized alpha 1-adrenergic receptor subtypes in functional rat thyroid cells, FRTL, with relation to iodide efflux, and have also examined the effect of TSH on alpha 1 receptor subtypes. FRTL cells grown in a medium containing 5 mU TSH/ml (6H cells) had five times the number of alpha 1 receptors of those maintained in TSH-free medium (5H cells) (11.2 fmol/10(6) cells compared with 2.0 fmol/10(6) cells). Pretreatment with chlorethylclonidine (CEC; 10 mumols/l), which inactivates only alpha 1b receptors, caused 98.8% and 97.0% decreases in the density of specific [3H]prazosin-binding sites in 5H and 6H cells respectively. LIGAND computer program analysis of the displacement curves for 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4 benzodioxane (WB4101) showed that FRTL cells contained mostly low-affinity WB4101 sites. Using the phenoxybenzamine inactivation method, we found a linear relationship between alpha 1 receptor density and the cytosolic free Ca2+ concentration response in FRTL cells. Pre-exposure of intact FRTL cells to CEC caused a 98.7% decrease in noradrenaline-stimulated maximal increase in cytosolic free Ca2+. Also, CEC and 3,4,5-trimethoxy-benzoic acid 8-(diethylamino) octyl ester (TMB-8), but not nicardipine, inhibited noradrenaline-stimulated iodine efflux. The results suggest that FRTL cells contain mostly the alpha 1b-adrenergic receptor subtype; that the alpha 1b receptors mediate cytosolic free Ca2+ and iodide efflux responses, and that TSH enhances these responses by increasing the alpha 1b receptor density without affecting the post-receptor mechanism.

Animals↗
PubMed1990

Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role.

Using the alpha 1-adrenoceptor subtype-selective antagonists chlorethylclonidine (CEC), WB4101, and 5-methyl-urapidil, we have examined the possible heterogeneity in the alpha 1-adrenoceptor populations in rabbit aorta. The alpha 1-adrenoceptor alkylating agent CEC selectively inhibited the phasic component of the norepinephrine-induced contractile response, with little effect on the tonic component. The alpha 1-adrenoceptor occupancy-response relationship defined by the phenoxybenzamine inactivation method was rectangular hyperbolic for the tonic response, whereas that for the phasic response was linear, indicating the different degree of receptor reserve for the two responses. Radioligand binding studies with the nonselective alpha 1-adrenoceptor antagonist radioligand 125I-BE2254 showed that 73-87% of the binding sites in rabbit aorta are CEC sensitive and they are predominantly low affinity sites both for WB4101 (pKd = 8.1) and for 5-methylurapidil (pKd = 7.1). Moreover, alpha 1-adrenoceptor-mediated phosphatidylinositol (PI) hydrolysis was CEC sensitive, and fractional inactivation of alpha 1 receptors with CEC showed equivalent increments in the reduction of PI hydrolysis and phasic contractile response, suggesting that both responses are linearly related to the CEC-sensitive receptor sites. The Schild plots for the competitive antagonists WB4101 and 5-methyl-urapidil against alpha 1a-adrenoceptor-selective agonist methoxamine-induced contraction were linear and had slopes not significantly different from unity, with a pA2 of 9.07 +/- 0.07 (n = 5) for WB4101 and 9.09 +/- 0.05 (n = 3) for 5-methyl-urapidil. However, the Schilod plots for these antagonists against norepinephrine were curvilinear. Computer-assisted analysis of these curvilinear Schild plots in a two-receptor system indicated that alpha 1-adrenoceptor populations responsible for the constrictive response are predominantly (approximately 80-90%) low affinity sites for the two antagonists (pKd approximately 8.1 for WB4101 and pKd approximately 7.1 for 5-methyl-urapidil) and a small population (approximately 10-20%) are high affinity sites (pKd approximately 9.1 for both WB4101 and 5-methyl-urapidil), which was in good agreement with radioligand binding studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1989

Desensitization of alpha 1 adrenoceptor-stimulated glycogen phosphorylase activity in vascular smooth muscle.

Desensitization of alpha 1-adrenoceptor-mediated activation of glycogen phosphorylase was investigated in rabbit aorta. Activation of glycogen phosphorylase by epinephrine was antagonized by the alpha 1-receptor selective antagonist prazosin but not by yohimbine (alpha 2-receptor selective) or by propranolol (beta-receptor antagonist). Preincubation of rabbit aortic ring segments for 5 h with norepinephrine (NE, 10(-5) M) led to a 30-fold loss in sensitivity and a 55% decrease in maximal activation of the enzyme by alpha agonists. Preincubation of aortic ring segments with phenylephrine (10(-5) M) in the presence of propranolol (10(-6) M) also caused desensitization of glycogen phosphorylase activation. The desensitization was heterologous since maximal activation of the enzyme by histamine or KCl was also markedly diminished in segments preincubated with NE. In contrast to these results, catecholamine-induced desensitization to alpha 1-adrenoceptor-mediated smooth muscle contraction in aortic ring segments resulted in loss in sensitivity but not maximal force of contraction on subsequent stimulation by alpha 1 agonists. These results suggest that the mechanism responsible for desensitization of glycogen phosphorylase is distal to receptor activation and may involve attenuation of responses to intracellular Ca2+-dependent enzymes which have limited reserve.

Animals↗
PubMed1989

The first demonstration of CGRP-immunoreactive fibers in canine hearts: coronary vasodilator, inotropic and chronotropic effects of CGRP in canine isolated, blood-perfused heart preparations.

CGRP-immunoreactive nerve fibers were histologically stained in the endocardium and perivascular layer of coronary vessels of canine hearts. To examine the physiological role of the CGRP in the heart function, effects of exogeneous CGRP on the hearts were studied using canine isolated, blood-perfused heart preparations. CGRP exerted dose-related potent vasodilator effects with a minimal increase in the developed tension of the papillary muscle, but slightly decreased the sinoatrial rate. The vasodilator effects were unaffected by the pretreatment of either atropine or propranolol. These specific functional effects on the coronary artery are well in accordance with the anatomical localization of CGRP. Taken together, CGRP seems to play an important role in the regulation of coronary vascular tone, while it has only a small functional role in inotropism and chronotropism in canine hearts.

Animals↗
PubMed1989

Glycogen phosphorylase activation by two different alpha 1-adrenergic receptor subtypes: methoxamine selectively stimulates a putative alpha 1-adrenergic receptor subtype (alpha 1a) that couples with Ca2+ influx.

We compared the effects of methoxamine on alpha 1-adrenergic receptor-mediated phosphorylase activation in rat hepatocytes and rabbit aorta. Although methoxamine is a potent agonist in activating phosphorylase of rabbit aorta, it had little effect in rat hepatocytes. Using the phenoxybenzamine inactivation method, we found that the quantitative relationship between 125I-BE2254 (125I-BE) binding capacity and maximal norepinephrine-stimulated phosphorylase activation was nonlinear in rabbit aorta, whereas it was linear in rat hepatocytes. The potency of methoxamine in inhibiting specific 125I-BE binding is significantly (p less than 0.05) higher in rabbit aorta (Kd, 96.4 +/- 7.7 microM), compared with rat hepatocytes (Kd, 283 +/- 16 microM). However, these quantitative differences could not fully explain the blunted [Ca2+]c and phosphorylase responses to methoxamine in rat hepatocytes. Treatment with chlorethylclonidine dose dependently suppressed 125I-BE binding sites and norepinephrine-induced phosphorylase activation in rat hepatocytes, whereas in rabbit aorta it resulted in only a 31% decrease in 125I-BE binding sites, with little effect on phosphorylase activation. Furthermore, alpha 1-adrenergic receptor-mediated cellular events of phosphatidylinositol (PI) hydrolysis and phosphorylase activation were unaffected by the removal of extracellular Ca2+ in rat hepatocytes, whereas both responses were markedly attenuated in rabbit aorta. The results indicate that two different alpha 1-adrenergic receptor subtypes activate glycogen phosphorylase, through different mechanisms for increasing [Ca2+]c in the two systems. In rat hepatocytes, alpha 1 receptors are closely linked to PI hydrolysis and Ca2+ release from intracellular stores and cause phosphorylase activation. In rabbit aorta, on the other hand, activation of alpha 1 receptors increases [Ca2+]c by Ca2+ influx from the extracellular fluid as well as by Ca2+ release, and both PI hydrolysis and phosphorylase activation are caused mainly by the Ca2+ entry. Methoxamine interacts with both chlorethylclonidine-sensitive and -insensitive alpha 1 receptor subtypes but selectively stimulates the alpha 1 receptor subtype that closely couples with the Ca2+ influx.

Animals↗
PubMed1989

Pharmacokinetic and pharmacodynamic principles of drug therapy in old age. Part 2.

In this Part 2, pharmacodynamic studies which have examined the possibility of true changes in drug "sensitivity" in old age are reviewed. In a variety of organ systems, age-related physiological changes are reflected in altered drug responsiveness in the elderly. Also, a better understanding of different pathophysiological background of disease in this age group leads to a more rational pharmacotherapeutic approach, which is exemplified in the recent drug therapy of hypertension in the elderly.

Aging↗
PubMed1989

Pharmacokinetic and pharmacodynamic principles of drug therapy in old age. Part 1.

Changes in pharmacokinetics and pharmacodynamics which occur with aging are reviewed. In Part 1, age-related alterations in pharmacokinetics, which deals with absorption, distribution, metabolism and elimination of drugs, are summarized. Special emphasis is placed on "drug clearance" which conceptual importance for the evaluation of drug elimination has only been recently recognized. Age-related physiological alterations and their influence on major determinants for each organ clearance are discussed.

Aged↗
PubMed1988

Simultaneous determination of metoprolol and alpha-hydroxymetoprolol in human plasma and urine by liquid chromatography with a preliminary observation on metoprolol oxidation in Japanese subjects.

A simple, sensitive, and highly reliable liquid chromatographic method using fluorescence detection is described for the simultaneous determination of metoprolol and alpha-hydroxymetoprolol in plasma and urine. This method involves a single extraction of the compounds with the internal standard pindolol from alkalinized plasma or urine into dichloromethane. A reconstituted aliquot with a mobile phase is injected onto a reversed-phase, Zorbax ODS column, and the detection is achieved by the excitation and emission wavelengths at 230 and 300 nm, respectively. The assay is reproducible and precise for metoprolol and alpha-hydroxymetoprolol in both plasma and urine samples, as judged by a coefficient of variation of less than 9.2% at all concentrations examined. The standard curves for metoprolol and alpha-hydroxymetoprolol are linear over 10-200 ng/ml in plasma and over 0.5-10 micrograms/ml in urine. The lower detection limit is 2 ng/ml for each of the compounds in plasma using a 0.5-ml sample. Preliminary data on the oxidation polymorphism of metoprolol in Japanese subjects are reported using the current assay method. In 183 Japanese subjects no poor metabolizer of metoprolol has been identified so far.

Chromatography, Liquid↗
PubMed1988

In vivo desensitization of glycogenolysis to Ca2+-mobilizing hormones in rat liver cells.

Rat hepatocytes contain several types of Ca2+-linked receptors, all of which stimulate glycogen breakdown by increasing cytosolic free Ca2+ concentration [( Ca2+]c). In vivo desensitization of this Ca2+ messenger system was studied in hepatocytes isolated from either pheochromocytoma (PHEO)-harboring and chronically norepinephrine (NE)-infused rats. Homologous desensitization for alpha 1-adrenergic receptor-mediated phosphorylase activation developed in the early stage of PHEO rats (3-4 wk after implantation), whereas, in the later stage of tumor development or in the NE-infused rats, phosphorylase responses to all Ca2+-mobilizing stimulations were subsensitive (heterologous desensitization). In the homologous desensitization, the [Ca2+]c response to alpha 1-adrenergic stimulation was selectively reduced. We found, using the phenoxybenzamine inactivation method, that there was a linear relationship between alpha 1 receptor density and the [Ca2+]c response; consequently, the blunted [Ca2+]c response to alpha 1-adrenergic stimulation could not be explained by the 34% downregulation of alpha 1 receptors seen in these rats. These results indicated that uncoupling at a step proximal to alpha 1 receptor-stimulated [Ca2+]c increase is also of primary importance in homologous desensitization of phosphorylase activation. On the other hand, heterologous desensitization also involved alteration(s) at steps distal to the rise in [Ca2+]c. Our data demonstrate that prolonged exposure to catecholamines results in desensitization of the [Ca2+]c mobilization pathway and may involve multiple mechanisms.

Adrenal Gland Neoplasms↗
PubMed1988

Beta adrenoceptors in the canine large coronary arteries: beta-1 adrenoceptors predominate in vasodilation.

Beta adrenoceptors of the canine large coronary artery were characterized by observing the effects of the subtype selective antagonists, metoprolol (beta-1) and ICI 118,551 (beta-2), on the vasodilator responses of isolated and perfused preparations to beta adrenoceptor agonists and in the radioligand binding assay. The integrity of the endothelium was checked by acetylcholine-induced vasodilations. Without any precontraction, isoproterenol, norepinephrine, epinephrine and procaterol (selective beta-2 agonist) dilated the canine large coronary artery pretreated with phentolamine (10(-5) M). The rank order of agonist potency was isoproterenol greater than norepinephrine greater than epinephrine greater than procaterol. The pA2 values for metoprolol and ICI 118,551 were determined by the antagonisms of the vasodilator responses to isoproterenol and procaterol. The slopes of Schild plots for metoprolol and ICI 118,551 against isoproterenol and the value for ICI 118,551 against procaterol were not significantly different from unity, but the value for metoprolol against procaterol was significantly less than unity. The pA2 value for metoprolol against isoproterenol was 7.48 and those values for ICI 118,551 against isoproterenol and procaterol was 7.19 and 7.25, respectively. These pA2 values are typical for beta-1 adrenoceptors. The beta adrenoceptors of the canine large coronary artery were examined further using an antagonist [125I]iodocyanopindolol as a ligand for the binding of beta adrenoceptors. The [125I]iodocyanopindolol binding to the canine coronary artery smooth muscle membrane was saturable with a KD of 63.7 pM and a total number of radioligand binding sites of 44 fmol/mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1988

Cardiomyopathy in a rat model of pheochromocytoma. Morphological and functional alterations.

To investigate the cardiac muscle damage observed in pheochromocytoma, New England Deaconness Hospital rats were implanted subcutaneously with a transplantable pheochromocytoma. The tumor was evident 4 weeks after transplantation. Approximately 5-6 weeks after transplant, systolic blood pressure was significantly increased in tumor-bearing animals (183 +/- 13 vs 119 +/- 7 in controls). At this time a cardiomyopathy with the following features was apparent in the tumor-bearing animals: multifocal lesions of enhanced interstitial and replacement fibrosis; granularity of the cytoplasm and contraction band necrosis; and mixed inflammatory infiltrates. Using a morphological scoring system from 0 (no cardiac damage) to 3 (complete involvement of the ventricular cross section studied), the pheochromocytoma animals had a cardiomyopathy score of 1.8 +/- 0.1, which is significantly greater than that found in age- and sex-matched controls: 0.4 +/- 0.1, p less than .001. A significant increase in the wet heart weights (1.28 +/- 0.07 vs. 1.12 +/- 0.04 in controls) was also observed in these animals, indicating the possibility of cardiac hypertrophy in the pheochromocytoma rats. There was a marked decrease in sensitivity to isoproterenol in isolated, electrically driven left atrial strips from pheochromocytoma rats. Isoproterenol's EC50 increased eightfold from 1.5 +/- 0.6 x 10(-8) M in controls to 1.3 +/- 0.4 x 10(-7) M in left atrial strips from the pheochromocytoma rats. However, there was no difference in maximal contractile response to isoproterenol in either the left atrial strips or in right or left ventricular papillary muscle strips. Also, there was no change in responsiveness of either left atrial or right ventricular muscle strips from pheochromocytoma hearts to contraction induced by 3.75 mM calcium chloride. However, the contractile response to calcium was enhanced in left ventricular papillary muscle from tumor-bearing animals (808 +/- 195 vs 372 +/- 101 mg tension in controls, p less than 0.05). These results demonstrate a catecholamine-induced cardiomyopathy in hearts from pheochromocytoma-bearing rats. Furthermore, the results demonstrate a functional beta-adrenergic receptor desensitization in isolated left atrial strips from tumor-bearing rats, whereas maximal contraction of heart muscle, induced by either isoproterenol or calcium chloride, remains intact.

Animals↗
PubMed1987

Effects of thyroid hormone on beta-adrenergic responsiveness of aging cardiovascular systems.

We have compared the effects of beta-adrenergic stimulation on the heart and peripheral vasculature of young (2-mo-old) and older (12-mo-old) rats both in the presence and absence of triiodothyronine (T3)-induced hyperthyroidism. The hemodynamic consequences of T3 treatment were less prominent in the aged hyperthyroid rats compared with young hyperthyroid rats (both in intact and pithed rats). There was a decrease in sensitivity of chronotropic responsiveness to isoproterenol in older pithed rats, which was apparently reversed by T3 treatment. The number and affinity of myocardial beta-adrenergic receptor sites measured by [125I]cyanopindolol were not significantly different in young and older control rats; also, beta-receptor density increased to a similar extent in both young and older T3-treated rats. The ability of isoproterenol to relax mesenteric arterial rings, markedly blunted in older rats, was partially restored by T3 treatment without their being any change in isoproterenol-mediated relaxation in the arterial preparations from young rats. The number and affinity of the beta-adrenergic receptors measured in the mesenteric arteries was unaffected by either aging or T3 treatment. The data suggest that effects of thyroid hormone and age-related alterations of cardiovascular responsiveness to beta-adrenergic stimulation are interrelated in a complex fashion with a net result that the hyperkinetic cardiovascular manifestations in hyperthyroidism are attenuated in the older animals.

Aging↗
PubMed1987

Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma.

Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.

Angiotensins↗
PubMed1987

Effects of triiodo-L-thyronine (T3)-induced hyperthyroidism on the cardiovascular alpha-adrenoceptor system in young and older rats.

We have compared the vasopressor response of alpha-adrenoceptor agonists in young (2 month-old) and older (12 month-old) pithed rats both in the presence and absence of triiodo-L-thyronine (T3)-induced hyperthyroidism. There was no age-related changes in the pressor response to either the alpha 1-selective agonist phenylephrine or the alpha 2-selective agonists clonidine and UK-14,304. However, T3-induced hyperthyroidism caused a selective reduction in postjunctional alpha 2-adrenoceptor-mediated pressor responses but not alpha 1-adrenoceptor-mediated ones in both age groups. In contrast to vascular alpha-adrenoceptors, there was an age-related decrease in the number of myocardial alpha 1-adrenoceptor sites measured by specific binding of [3H]prazosin. With thyroid hormone treatment, the density of ventricular alpha 1 receptors was found to be further reduced even in the older rats. These results suggest that thyroid hormone and aging have different influences on the cardiovascular alpha-adrenoceptor system and that these two physiological variables are independently interrelated.

Aging↗
PubMed1987

Characterization of vasopressor response to sympathetic stimulation in the pithed rat: differential regulation of neuronally stimulated and blood-borne catecholamine-stimulated pressor responses in rats harboring pheochromocytoma.

The vasopressor response to sympathetic stimulation in the pithed rat was characterized both by analyzing the effects of chemical sympathectomy, adrenalectomy and selective antagonists on the vasopressor response and by measurement of changes in plasma concentrations of catecholamines. Stimulation of the spinal sympathetic outflow evoked a biphasic pressor response: an initial transient component was caused mainly by postganglionic sympathetic nerve stimulation (the direct response); a slowly developing secondary component was mediated predominantly by circulating catecholamines released from the adrenal medulla (the adrenal response). Parallel analysis of plasma catecholamines showed that the rise in epinephrine appeared to be closely related to this adrenal component. The pressor response in adrenalectomized rats was selectively blocked by prazosin but not by yohimbine; however, in sympathectomized rats, the pressor response was abolished by prazosin and yohimbine together but not by either drug given alone. These results suggest that the direct, neurogenic component is mediated mainly by alpha-1 adrenoceptors whereas the secondary, adrenally mediated response occurs by activation of both alpha-1 and alpha-2 adrenoceptors. Furthermore, the in vivo regulation of each component of the pressor response was studied in rats harboring pheochromocytoma (PHEO), a tumor causing marked elevations in endogenous catecholamine concentrations. In PHEO rats, the direct pressor response was found to be relatively intact but the adrenal response was blunted. Inasmuch as there was normal rise in plasma epinephrine to electrical stimulation in PHEO rats, the results suggest a differential regulation of neuronally stimulated and blood-borne catecholamine-mediated pressor responses in PHEO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗