Dopamine (3,4-dihydroxyphenylethylamine) is considered to be the immediate metabolic precursor of norepinephrine (1), from which it differs by the absence of a P-OH group. Despite this chemical similarity, previous studies of the action of dopamine (2-9) have demonstrated that many of the circulatory and metabolic effects of this catecholamine are different from those produced by norepinephrine. Horwitz, Fox, and Goldberg (6) observed that intravenous administration of dopamine to normal subjects produced consistent increases in cardiac output and either decreased or did not change peripheral resistance. Norepinephrine, on the other hand, decreases or does not change cardiac output and increases peripheral resistance in normal subjects (10). The circulatory effects of dopamine are potentiated by monoamine oxidase inhibitors to a much greater extent than are those of norepinephrine (9). Dopamine also contrasts with norepinephrine in its failure to increase circulating free fatty acids (7,8). These differences suggest that the effects of

We determined the effect of perfusion pressure on the distribution of blood flow within the renal cortex of the anesthetized dog. Total blood flow to the denervated kidney was measured by an electromagnetic flowmeter and perfusion pressure was manipulated over the autoregulatory range (136 to 81 mm Hg) by an aortic clamp. Distribution of cortical blood flow was determined by the radioactive microsphere technique. Tissue perfusion rates of four cortical zones of equal thickness differed significantly from each other at normal arterial pressure. In sequence from superficial to deep, perfusion of the cortex zones averaged 4.18, 6.80, 3.07, and 1.68 ml • g" 1 • mirr 1 . Aortic constriction significantly reduced perfusion of the outer cortical zone and augmented perfusion of the inner two cortex zones. Twelve percent of total renal blood flow was redistributed by pressure reduction. Atropine, 1 mg/kg, had no effect on cortical perfusion rates at either pressure. The influence of microsphere diameter and density on cortex perfusion rates was systematically studied and found to be minor. This observation implies that the microsphere method is valid for measuring distribution of blood flow within the renal cortex. We conclude that zones of the renal cortex are perfused at different rates and respond differently to changes in arterial pressure. ADDITIONAL KEY WORDSredistribution of flow autoregulation radioactive microspheres atropine regional blood flow renal medulla renal cortex• It has been demonstrated by a wide variety of methods that tissue perfusion rates within the kidney are heterogenous (1-6). In general, interest has centered on differences in the perfusion rates of the cortex and medulla. Although distribution of blood flow within the renal cortex has received less attention, evidence favoring homogenous cortical perfusion has been obtained by several methods which readily detect differences between cortical and outer medullary perfusion rates (3,6 Received January 30, 1970; accepted for publication August 10, 1970. addition, heterogenous cortical perfusion has been observed during hemorrhagic hypotension (7), splanchnic nerve stimulation (8), and infusion of angiotensin (9). The relevance of possible heterogeneity of cortex perfusion has been increased by recent observations of differences between the glomerular filtration rates of superficial and juxtamedullary nephrons (10).In this investigation, we have specifically analyzed distribution of blood flow within the renal cortex. We approached the problem by the use of radioactive microspheres (11-13). This technique was well suited to our objectives because microsphere emboli of appropriate size are arrested within or adjacent to the first capillary bed they encounter. Since in the kidney, glomerular capillaries are the first to be perfused, the location of microspheres is necessarily cortical. We studied the renal circulation under conditions of normal and reduced perfusion pressure. Pressure reduction within the 572McNAY, ABE autoregulatory ran...

• We have recently demonstrated that intravenous administration of the naturally occurring catecholamine, dopamine, increases effective renal plasma flow, glomerular filtration rate, and sodium excretion in normal human subjects.1 Since renal plasma flow increased in the absence of an alteration in mean arterial pressure, it was concluded that renal vascular resistance was decreased by dopamine. Comparable effects were observed in the dog. The present study was undertaken to characterize these findings more fully. The effects of intravenous dopamine infusion on directly measured renal blood flow and blood pressure were compared with those of isoproterenol and norepinephrine, chosen as catecholamines with strong vasodilator and vasoconstrictor effects, respectively. In addition, renal blood flow responses to direct renal arterial injections of these three agents were studied. To determine whether the renal vascular responses to dopamine were typical of other vascular beds, comparable experiments studying femoral blood flow responses to intraarterial injections of dopamine, isoproterenol, From the Department of Pharmacology and the Department of Medicine (Section of Clinical Pharmacology), Emory University School of Medicine, Atlanta, Georgia.Supported by Grants H-649I and HE-5582 from the U. S. Public Health Service and grants from the American Heart Association, Georgia Heart Associations, the Heart Associations of Palm Beach and Martin Counties, Florida.A portion of the material in this paper has previously appeared in abstract form in Clinical Research 11: 248, 1963 and The Pharmacologist 5: 269, 1963.Accepted for publication November 19, 1964. and norepinephrine were also performed. We found that dopamine is unique among vasoactive agents, since it produces renal vasodilatation and femoral vasoconstriction.Methods Mongrel dogs ranging in weight from 11 to 20 kg were anesthetized by the intravenous injection of either pentobarbital, 25 mg/kg, or a combination of pentobarbital, 15 mg/kg, and barbital, 220 mg/kg. Supplemental maintenance doses were administered as needed.Blood flow in the left femoral or left renal artery was measured continuously by means of an electromagnetic flowmeter.* The kidney itself was not manipulated, and adjacent structures were disturbed minimally. Renal nerves were left intact except in four experiments in which all visible nerve structures entering the kidney were divided prior to drug administration. In experiments in which femoral artery blood flow was studied, the hind limb was acutely denervated by the division of the femoral and sciatic nerves, and circulation through the paw was occluded using a crushing device applied at the level of the lower tibia. The zero-flow base line and phase adjustments of the flowmeter were performed immediately after application of the flow probe and at intervals throughout each experiment by mechanical occlusion of the artery distal to the flow probe. Two or three separate calibrations of each flow probe were performed during the series of ex...

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The pharmacokinetic-pharmacodynamic model for 24-hour ABPM can be used to estimate the concentration-effect relationship of antihypertensive drugs.