Biomedical subjects
W M Manger
Publications and source records attributed to W M Manger.
Pheochromocytoma.
None of the endocrine causes for hypertension is more fascinating and challenging for the clinician than pheochromocytoma. Its protean manifestations can make diagnosis difficult, yet its sinister prognostic implications demand prompt recognition and expert management. Diagnosis depends on clinical suspicion, demonstration of high levels of free catecholamines in the plasma or urine, or high localization of the tumor by appropriate imaging techniques that include CT scanning, MR imaging, and 131I-MIBG scintigraphy. Surgical extirpation is the treatment of choice unless the risk of operation is overwhelming or distant metastasis has already occurred. Successful outcome demands a team approach, taking advantage of the experience, skill, and expertise of the surgeon, anesthesiologist, and internist.
Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.
We have previously shown that renal vascular resistance is less in Dahl salt-sensitive rats than salt-resistant rats fed 1% NaCl diets; however, renal vascular resistance increases before nonrenal vascular resistance as salt-sensitive rats develop hypertension when fed 8% NaCl diets. When salt-resistant rats are given 8% NaCl diets, renal vascular resistance decreases. The current study reports effects of atrial natriuretic peptide, nitroprusside, norepinephrine, angiotensin II, and endothelin-1 on renal and nonrenal vascular resistance in prehypertensive salt-sensitive and salt-resistant rats given 1% NaCl diets; doses used did not affect blood pressure. Resistance of nonrenal vessels in salt-sensitive and salt-resistant rats responded similarly to dilators or constrictors. However, atrial natriuretic peptide and nitroprusside decreased renal vascular resistance of salt-resistant rats (by 65%, p less than 0.01) but not that of salt-sensitive rats. Norepinephrine, angiotensin II, and endothelin-1 increased renal vascular resistance in salt-sensitive rats by 126%, 135%, and 135%, respectively (p less than 0.01); norepinephrine and angiotensin II did not change renal vascular resistance of salt-resistant rats, but endothelin-1 decreased renal vascular resistance in salt-resistant rats by 30% (p less than 0.01). Reactivity of nonrenal blood vessels in prehypertensive salt-sensitive and salt-resistant rats was similar when infused with dilators or constrictors in doses used. By contrast, renal vessels of salt-sensitive rats did not dilate in response to atrial natriuretic peptide and nitroprusside but were hypersensitive to norepinephrine and angiotensin II. Endothelin-1 caused renal vasoconstriction in salt-sensitive rats and renal vasodilation in salt-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Report of the First Irvine Page symposium, September 1990, Baltimore, USA.
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Dual hemodynamic mechanisms for salt-induced hypertension in Dahl salt-sensitive rats.
Cardiac output, blood volume, total peripheral resistance, and renal blood flow were measured in awake salt-sensitive and salt-resistant Dahl rats on normal rat chow (1% NaCl) and on high salt (8% NaCl) diets. Rats were studied after 4, 8, and 46 weeks on a 1% NaCl diet and after 4 and 8 weeks on an 8% NaCl diet. Salt-sensitive rats on 8% NaCl for 4 weeks developed systolic hypertension; by 8 weeks they developed greater systolic and also diastolic hypertension. Salt-resistant rats on 8% NaCl remained normotensive throughout the studies, although renal resistance decreased (p less than 0.05). At 4 weeks, hypertension in salt-sensitive rats on 8% NaCl was caused by increased blood volume and cardiac output (p less than 0.05), with normal total peripheral resistance. At 8 weeks, hypertension was due to increased total peripheral resistance (p less than 0.05); cardiac output was below normal despite persistent elevation of blood volume (p less than 0.05). Salt-sensitive rats on 1% NaCl for 46 weeks were hypertensive, with elevated total peripheral resistance (p less than 0.05); cardiac output decreased (p less than 0.05), whereas blood volume remained unchanged. Salt-resistant rats on 1% NaCl remained normotensive with no charges in hemodynamics. Salt-sensitive rats on 8% NaCl for 4 weeks had an increase in renal vascular resistance but no significant change in nonrenal resistance or total peripheral resistance. The increased total peripheral resistance in salt-sensitive rats on 8% NaCl for 8 weeks and on 1% NaCl for 46 weeks was a reflection of increases of both renal and nonrenal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Catecholamines, cocaine toxicity, and their antidotes in the rat.
Acute lethal cocaine intoxication in the rat induces significant increases of plasma dopamine, norepinephrine, and epinephrine concentrations associated with cardiac functional and morphologic changes. Nitrendipine (a calcium channel antagonist) administered 5 min following cocaine administration lowers catecholamine concentration and restores cardiovascular function to normal, while preventing lethality, and so does enalaprilat (an enzyme-converting inhibitor) administration with diazepam. Cocaine cardiac toxicity in the rat appears to be associated with a significant stimulation of the sympathoadrenal and a sustained elevated plasma concentration of epinephrine. The renin angiotensin system also appears to be activated.
Cocaine, catecholamines and cardiac toxicity.
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Interactions of nimodipine and cocaine on endogenous catecholamines in the squirrel monkey.
The effects of nimodipine on the cocaine-induced alterations in blood pressure, heart rate, and plasma catecholamines were studied in the squirrel monkey. Cocaine in intravenously administered doses of 0.5, 1, and 2 mg/kg produced significant increases in blood pressure and significant decreases in heart rate. These cardiovascular changes were associated with transient episodes of arrhythmias and with significant increases in plasma concentrations of dopamine, epinephrine, and norepinephrine. Nimodipine, 1 micrograms/kg/min for 5 min administered intravenously 5 min after cocaine, corrects the cardiovascular and plasma catecholamine concentration changes induced by this alkaloid. The same dose of nimodipine administered 5 min before cocaine prevents elevations of blood pressure. Plasma catecholamine increments are also prevented except for the highest dose of cocaine. Cardiovascular changes induced by cocaine administration in the squirrel monkey are temporally associated with significant increments in plasma catecholamines. Administration of nimodipine prevents or minimizes these endocrine and physiologic changes.
Cocaine, catecholamines and cardiac toxicity.
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Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.
This study was performed with Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats to detect differences in cardiovascular hemodynamics and renal responses that might be involved in initiating salt-induced hypertension in DS rats. The effects of 4 weeks of 8% NaCl diet were studied in conscious, male DR and DS rats in which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANF) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase in ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes in blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation in all regions studied in DR rats; DS rats showed vasodilation in all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase in cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased in DR rats but not in DS rats. It is concluded that the primary hemodynamic disturbance in DS rats with salt-induced hypertension is an increase in cardiac output caused by blood volume expansion in the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF.
Pheochromocytoma.
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Pseudopheochromocytoma and cardiac arrest associated with phenylpropanolamine.
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Psychiatric manifestations in patients with pheochromocytomas.
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Diagnosis and management of pheochromocytoma.
Pheochromocytomas arise from chromaffin tissue, usually in the adrenal medulla, and are a cause for curable hypertension. Nearly all patients with this tumor are symptomatic, the most common symptoms being headache, palpitations and inappropriate perspiration. Diagnosis is confirmed by finding high levels of plasma catecholamines or increased excretion of catecholamine metabolites (metanephrines, vanillymandelic acid) in the urine. Localization of tumors(s) is important for the surgeon and is accomplished by CT scan, 131I-metaiodobenzylguanidine scintiscans or abdominal aortography. Treatment is surgical extirpation by an experienced team after depleted plasma volume has been replenished. Ten percent of tumors are malignant, 10% are bilateral in the adrenal medullae and 10% are extra-adrenal.
Pheochromocytoma: a clinical and experimental overview.
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Desensitization of beta-adrenergic receptors by pheochromocytoma.
Prolonged stimulation of cells by beta-adrenergic receptor agonists may lead to diminished responsiveness of the cells to subsequent activation by catecholamines. This phenomenon has been termed desensitization; the mechanism(s) for desensitization may involve an apparent loss in the number of beta-adrenergic receptors or an alteration in receptor-effector coupling. We have examined the consequences of prolonged stimulation of beta-adrenergic receptors in an interesting rat model harboring pheochromocytoma. New England Deaconess Hospital rats with transplanted pheochromocytomas developed systolic hypertension and plasma norepinephrine concentrations approximately 40-fold greater than controls. beta-Adrenergic receptors were quantitated in several tissues from controls and rats with transplanted pheochromocytoma using the beta-adrenergic receptor antagonist [125I]iodocyanopindolol. Down-regulation of beta 1-receptors was found in heart tissue (22.8 vs. 13.6 fmol/mg protein; P less than 0.001) and adipocytes (29,400 vs. 2,800 sites/cell; P less than 0.001). Also, maximal isoproterenol-stimulated cAMP accumulation in isolated adipocytes was diminished in pheochromocytomic animals (13.1 vs. 4.9 pmol cAMP/10(5) cells/min; P less than 0.05). Interestingly, there was no change in beta-receptors in lung and mesenteric artery, which predominantly contain beta 2-receptors. Furthermore, the competition curves of isoproterenol in the heart membranes from control and pheochromocytomic rats in the absence and presence of guanylylimidodiphosphate indicated uncoupling of the beta-adrenergic receptors in pheochromocytomic animals. Rats with pheochromocytoma secreting large amounts of norepinephrine provide a valuable model system for studying the in vivo development of desensitization.
Heart imaging in the diagnosis of pheochromocytoma and assessment of catecholamine uptake.
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Catecholamines in normal and abnormal cardiac function.
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