The effect of diazoxide on catecholamines

Zarday, Zoltan; Viktora, Josef K.; Wolff, Frederick W.

doi:10.1016/0026-0495(66)90023-0

Cited by 44 publications

(13 citation statements)

References 9 publications

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“…Various vasodilator antihypertensives have been shown to cause reflex increase in sympathetic tone as reflected by increases in heart rate (5,7,17) and blood (18) or urinary catecholamines (9). In the present study, all patients showed an.…”

Section: Resultssupporting

confidence: 50%

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

O’Malley¹,

Velasco²,

Wells³

et al. 1975

J. Clin. Invest.

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A B S T R A C T A study was made of the possible mechanism(s) underlyingminoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol.Minoxidil lowered mean arterial pressure 31.6±3.3 mm Hg, mean ±SEM. There was an associated increase in both PRA, 6.26+2.43 ng/ml/h, and heart rate, 21.4±2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1+±1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil.Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism (s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure.

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Section: Resultssupporting

confidence: 50%

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

O’Malley¹,

Velasco²,

Wells³

et al. 1975

J. Clin. Invest.

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“…It remains uncertain, however, whether the increased sympatho-adrenal ac tivities were mediated reflexly by the hypotensive action of dia zoxide or by other mechanisms. The latter workers [15,16,21] stated that the decrease in plasma insulin levels produced by dia zoxide is most likely due lo I lie increased catecholamine release, since NE and epinephrine have been demonstrated to be very effective in inhibiting insulin secretion [7,18]. In the present study, diazoxide induced a significant FFA release from isolated fat cells in the glucose-free medium.…”

Section: Discussionsupporting

confidence: 55%

“…It has been well estab lished that the decrease in insulin secretion per se increases not only blood glucose lnil also plasma FFA levels and vice versa [7]. In contrast, Tabachnick et al [15,16] and Zarday et al [21] showed that diazoxide increases plasma catecholamine levels, thereby increasing both blood glucose and FFA levels. It remains uncertain, however, whether the increased sympatho-adrenal ac tivities were mediated reflexly by the hypotensive action of dia zoxide or by other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, diazoxide was found lo markedly increase plasma levels of free fatty acids (FFA) in human subjects [19] and in dogs [16]. The lipolytic action of diazoxide could be mediated through (a) Ihe increased secretion of catecholamines [15,16,21] or through, (b) Ihe inhibition of insulin secretion [1,4,12]. However, presently it is not clear whether diazoxide can exert a direct lipolytic action on adipose tissue without a concomitant influence of epinephrine and/or insulin.…”

mentioning

confidence: 99%

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Effect of Diazoxide on Lipolysis in Isolated Rat Fat Cells

Nakano¹,

Ishii²,

Gin³

1968

Pharmacology

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“…It would appear that this hyperglycemic ac-tion is exerted through both pancreatic (6)(7)(8)(9) and extrapancreatic effects (10,11). The extrapancreatic effects have been attributed to diazoxide-induced increase in circulating catecholamines (12)(13)(14). This conclusion is supported by the reported inhibition of diazoxide hyperglycemia by prior adrenalectomy and by the administration of adrenergic receptor-blocking agents (11,(15)(16)(17), although other extrapancreatic effects not mediated via the catecholamine response may exist (18).…”

Section: Introductionmentioning

confidence: 97%

Diazoxide effects on biphasic insulin release: “adrenergic” suppression and enhancement in the perifused rat pancreas

Burr¹,

Marliss²,

Stauffacher³

et al. 1971

J. Clin. Invest.

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A B S T R A C T An in vitro system for perifusion of rat pancreas has been used to investigate the effects of diazoxide on glucose-induced insulin release. Administration of diazoxide with a stimulating concentration of glucose produced a dose-dependent suppression of insulin release. This effect was partly reversed by phentolamine. In the presence of nonstimulatory-concentrations of glucose, diazoxide plus phentolamine, but neither alone, stimulated a biphasic release of insulin similar to that observed with 1-isopropyl norepinephrine. A prior period of perifusion with a low concentration of diazoxide enhanced the primary component of subsequent glucose-stimulated insulin release, an effect inhibited by addition of either phentolamine or propranolol to the diazoxide during this "prestimulation" period. These effects are similar to those observed with epinephrine. By contrast with epinephrine however, increasing the concentration of diazoxide during the period before glucose stimulation enhanced both the primary and secondary components of subsequent glucoseinduced insulin release. These data suggest that at least some of the direct effects of diazoxide on the pancreas are mediated through a-and P-adrenergic receptor mechanisms.

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The effect of diazoxide on catecholamines

Cited by 44 publications

References 9 publications

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

Effect of Diazoxide on Lipolysis in Isolated Rat Fat Cells

Diazoxide effects on biphasic insulin release: “adrenergic” suppression and enhancement in the perifused rat pancreas

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