Prominent actions of autonomic drugs on metabolism include the effects on carbohydrate metabolism, on fat metabolism, on oxygen consumption, and on electrolyte metabolism. I t is well established that catecholamines produce effects in each of these areas of metabolism. In certain cases, the responses are known to occur also in response to direct electrical stimulation or in response to reflex activation of sympathetic nerves. The known effects of parasympathetic nerves or of acetylcholine on energy metabolism are relatively limited. One action of acetylcholine on cardiac glycogen metabolism was discovered by us a number of years ago (Vincent & Ellis, 1959). Since this action of acetylcholine has the overall characteristics of a new adrenergic blocking effect, it is appropriate to mention it in this symposium.Acetylcholine or carbaminoylcholine was found to inhibit epinephrineinduced glycogenolysis in isolated guinea pig hearts (Vincent & Ellis, 1963), to inhibit the activation of phosphorylase in the rat heart in situ (Hess et al. 1962), and to reduce the rate of cyclic AMP (adenosine 3',5'-monophosphate) formation in normal or epinephrine-stimulated cyclase system in subcellular particles from the heart (Murad et al., 1962). I t is of considerable interest that this effect of acetylcholine on epinephrine-induced glycogenolysis occurs in the hearts of several species (Blukoo-Allotey & Vincent, 1965), but it has not been possible t o demonstrate the effect on preparations of liver, diaphragm, or smooth muscle (unpublished observations) or on the adenyl cyclase system prepared from tissues other than the heart (Murad et al., 1962).The newer adrenergic blocking agents, which are the central theme of this symposium, are making major contributions to pharmacology. They are potential therapeutic agents by virtue of their ability to produce selective antagonisms not possible only a few years ago. Their importance to autonomic pharmacology, it appears to us, are two-fold:1. They supply long-needed tools with which to analyze aspects of sympathetic activity on responses not inhibited in a practical or selective manner by previously known adrenergic blocking agents.
The male spontaneously hypertensive rat (SHR) Duarte, Zhang, and Ellis induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated a f e r a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the infruence of gender and strain on the response to &C in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wstar-Kyoto (WKY) rats demonstrated signiJicant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors f o r RC-RD, similar to those characterized in humans for RC-RE develop spontaneously without requiring any special treatment or surgical intervention.
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