Epinephrine-induced hepatic potassium movements before and after adrenergic blockade.

The epinephrine-induced loss and subsequent uptake of K+ by the liver was studied by measuring hepatic arterio-venous K+ differences and splanchnic blood flows in anesthetized dogs with chronically implanted portal vein catheters and celiac and superior mesenteric artery flow probes. When epinephrine was administered intraportally, neither alpha- nor beta-adrenergic blockade, singly or in combination, had significant effects upon the hyperkalemic or the hypokalemic phases in either hepatic venous or systemic arterial blood. It was concluded that the movements of K+ into and out of the liver caused by epinephrine are not mediated by the classical adrenergic receptors as defined by inhibition by specific blocking agents.     

Hepatic sodium-potassium exchange induced by adrenomimetic amines.

The effects of catecholamines on hepatic K+ and Na+ movements were studied in anesthetized dogs by measuring systemic arterial and hepatic venous electrolyte composition following intraportal injections of adrenergic agonists. All catecholamines studied caused the initial loss and subsequent uptake of K+ by the liver. The loss of hepatic K+ was accompanied by an uptake of Na+ at a 1:1 ratio. This accumulation of Na+ continued, although at a slower rate, for at least 8 min. Epinephrine and norepinephrine were much more potent in these effects than either phenylephrine or isoproterenol. Neither alpha- nor beta-adrenergic blockade, singly or in combination, had an appreciable effect on the magnitude or duration of the observed ion shifts. It is concluded that the predominant effect of catecholamines is to produce a net accumulation of hepatic Na+, and that the mechanism governing hepatic ion movements is nonadrenergic as defined by stimulation by specific adrenergic agonists and inhibition by specific adrenergic antagonists.     

Structure--activity relations for the acceleration of efflux of noradrenaline from adrenergic nerves in rabbit atria by sympathomimetic amines.

Atria from reserpine-pretreated rabbits were exposed to pargyline to inhibit monoamine oxidase (amine oxidase (flavin-containing) EC 1.4.3.4) and subsequently incubated in (-)-[3H]noradrenaline to allow the cytoplasmic accumulation of amine in adrenergic nerves. The structure-activity relations for acceleration of efflux of cytoplasmic amine were examined. The most potent agents studied were (+)- and (-)-amphetamine, beta-phenethylamine, phentermine, and mephentermine. Ability to accelerate efflux was reduced by addition of phenolic hydroxyl groups, by phenolic methylation, by beta-hydroxylation, and by N-substitution. The structure-activity relations for acceleration of efflux differ notably from those for uptake, inhibition of uptake, or release of noradrenaline from adrenergic nerves, reported in previous studies. The ability and potency of a given phenethylamine derivative to accelerate the efflux of cytoplasmic noradrenaline is probably determined by such factors as the lipid solubility of the amine, the affinity of the amine for the uptake and efflux site(s) for noradrenaline, and competition for any reserpine-resistant intraneuronal binding sites.     

Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade.

Glucose utilization increases markedly in the normal dog during stress induced by the intracerebroventricular (ICV) injection of carbachol. To determine the extent to which insulin, glucagon, and selective (alpha/beta)-adrenergic activation mediate the increment in glucose metabolic clearance rate (MCR) and glucose production (R(a)), we used five groups of normal mongrel dogs: 1) pancreatic clamp (PC; n = 7) with peripheral somatostatin (0.8 microg x kg(-1) x min(-1)) and intraportal replacement of insulin (1,482 +/- 84 pmol x kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)) infusions; 2) PC plus combined alpha (phentolamine)- and beta (propranolol)-blockade (7 and 5 microg x kg(-1) x min(-1), respectively; alpha+beta; n = 5); 3) PC plus alpha-blockade (alpha; n = 6); 4) PC plus beta-blockade (beta; n = 5); and 5) a carbachol control group without PC (Con; n = 10). During ICV carbachol stress (0-120 min), catecholamines, ACTH, and cortisol increased in all groups. Baseline insulin and glucagon levels were maintained in all groups except Con, where glucagon rose 33%, and alpha, where insulin increased slightly but significantly. Stress increased (P < 0.05) plasma glucose in Con, PC, and alpha but decreased it in beta and alpha+beta. The MCR increment was greater (P < 0.05) in beta and alpha+beta than in Con, PC, and alpha. R(a) increased (P < 0.05) in all groups but was attenuated in alpha+beta. Stress-induced lipolysis was abolished in beta (P < 0.05). The marked rise in lactate in Con, PC, and alpha was abolished in alpha+beta and beta. We conclude that the stress-induced increase in MCR is largely independent of changes in insulin, markedly augmented by beta-blockade, and related, at least in part, to inhibition of lipolysis and glycogenolysis, and that R(a) is augmented by glucagon and alpha- and beta-catecholamine effects.     

Tissue blood flow and the sympathomimetic amines

In the arteries, blood flow and blood pressure are pulsatile in nature (Roston, 1962a; Roston 1962b). The patterns of blood movement and mural distension in the arteries are important because they may be associated with life-threatening degenerative changes in the arterial walls. As the vascular channels narrow, the pulsation decreases. At the level of the capillaries, almost no pulsation exists (Best and Taylor, 1961). The tissues are affected by the direct flow in the capillaries and not by the pulsation in the arteries. Thus, such quantities as pulse pressure, systolic pressure, and diastolic pressure which characterize blood movement in the arteries are not important as far as the tissues are concerned. Rather, the average pressure and flow in the capillaries are the quantities significant for tissue blood flow. The present study analyzes the local blood circulation in a typical tissue. Logical extension of this analysis results in insights into the physiological behavior of the circulation which integrate a considerable body of experimental data.     

Blockade of adrenergic responses by halogenated phenyl-2-halogenoethyl amines

The action of halogenated phenyl 2-halogenoethylamines on adrenergic α-receptor sites of the rat vas deferens was studied. The effect of halogen (Br) substituents in the phenyl nucleus resulted in the following differences in activity: para > meta - para > meta > ortho. All compounds possessed a short duration of action; recovery from adrenergic blockade was complete within 120 min. Exposure of tissues to phenoxybenzamine, after complete recovery from adrenergic blockade by the test compounds, did not alter the magnitude of initial blockade but sharply reduced the duration of action of phenoxybenzamine. These results are discussed in terms of a model which proposes at least 2 sites of action for 2-halogenoethylamines at the adrenergic α-receptors of the rat vas deferens.     

Chemically induced vasospasm: the effect of ischemia, vessel occlusion, and adrenergic blockade

Vasospasm in revascularized tissue can compromise tissue perfusion even though the microsurgical anastomoses remain patent. Circulating catecholamine stimulates peripheral vasoconstriction. Chemical vasospasm was induced by the intraarterial administration of norepinephrine to denervated rat hind limbs. Heel pad blood flow was assessed by laser-Doppler velocimetry. Mean blood flow was 463 +/- 106 in the denervated leg and 337 +/- 50 in the opposite (intact) leg (p less than 0.01). Flow in the denervated leg decreased 78 percent (463 +/- 106 to 100 +/- 23) within 5 minutes of norepinephrine administration and did not return to normal for 30 minutes. Norepinephrine administration in the presence of 1 and 3 hours of ischemia decreased flow at 5 minutes to 6.6 and 6.0 percent of normal, respectively (31 +/- 14, 28 +/- 14, control 100 +/- 23; p less than 0.001). Administration of intraarterial norepinephrine distal to a femoral artery occluded for 1 and 5 minutes reduced flow following clamp release to 11.2 and 7.1 percent of normal 5 minutes after clamp release (52 +/- 9, 33 +/- 7, control 100 +/- 23; p less than 0.001). Comparison of the 1-minute and 5-minute groups to each other showed a significant flow decrease in the 5-minute group (p less than 0.007). This indicates that the observed decrease in flow was related both to the presence of a vessel occlusion and to the length of the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)