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HANDBOOK OF PHYSIOLOGY 



CIRCl'LATION II 



pump into hypertensive ranges. Above ca. 200 mm Hg, 

 renal blood flow by rotameter increased with in- 

 creases in perfusion pressure to 280 mm Hg so that a 

 limit to the regulatory mechanism was reached at 

 about 200 mm. Yet GFR remained constant at the 

 higher pressures. DeWardener & Miles (73) con- 

 firmed the sigmoid nature of the pressure-flow curve 

 at high pressures and extended the observations on 

 the effect of hemorrhage. The pressure-flow curve 

 during hemorrhage fell markedly below the control 

 curve and assumed approximate linearity; the sus- 

 tained vasoconstriction had apparently impaired or 

 abolished the autoregulation. Likewise, prolonged 

 perfusion (4-5 hours) also was found to impair auto- 

 regulation. 



Mechanism of Autoregulation 



Possible mechanisms which might account for auto- 

 regulation have been explored in several reviews 

 (280, 343, 344). Mechanisms suggested were: a) 

 "metabolic theory" or reactive hyperemia theory; b) 

 intrarenal vascular reflex control; c) changes in vis- 

 cosity of blood as a factor in changes in renal 

 resistance, the ''viscosity theory," as exemplified by 

 the cell separation theory of Pappenheimer & Kinter 

 (240); d) the "tissue-pressure" theory, in which 

 changes in arterial, venous, and ureteral pressures 

 in varying degrees create changes in intrarenal pres- 

 sure, which in turn affect blood flow; and e) the 

 "myogenic theory" or vasoconstrictor theory, whereby 

 active changes in the smooth muscles of the arterioles 

 (afferent), in response to changes in intraluminal 

 pressure, regulate flow. 



the "metabolic theory." This was suggested by 

 Selkurt (280) as a possible explanation for the re- 

 duced vascular resistance manifested in the kidney 

 with moderate reduction in perfusion pressure. In- 

 creased production, or reduced removal, or both, of 

 (hyperemia-producing) metabolites resulting from 

 the impaired flow and hypoxia, might cause the ob- 

 served vascular dilatation. Typically, flow drops im- 

 mediately on decrease in pressure, but improves in 30 

 sec to 1 min (120, 258). When pressure is released, an 

 "overshoot" occurs, which restores in 30 sec to 1 min. 

 More difficult to explain is the increased resistance 

 which develops when pressure is suddenly raised. If 

 one speculates that a base-line production of 

 metabolites is the case for the kidney, then an immedi- 

 ate increase in flow as pressure is raised might rapidly 

 wash out metabolites responsible for the resting caliber 



of the resistance vessels, resulting in a net reduction in 

 caliber. A similar possibility has been considered by 

 Haddy et al. (124). 



Some support for a metabolic mechanism was 

 offered by the finding that kidneys perfused by pump 

 with hypoxic venous blood demonstrated hyperemia 

 (278), but the possibility of preformed metabolites in 

 the venous blood which might dilate the renal ar- 

 terioles must be held open. As earlier mentioned, the 

 peculiar flow-limited characteristic of the kidney may 

 make it more susceptible to hypoxic states. Perhaps 

 stronger support was the demonstration by Sarre & 

 Ansorge (262) that the dog kidney exhibited "re- 

 active hyperemia" to short bouts (1—5 min) of clamp- 

 ing of the renal arteries. The responses were usually 

 modest, but in two instances flow increased by 1 50 

 and 1 73 per cent. Flow was restored to normal in 

 these cases in about 5 min. Since a venous outflow 

 method was used, filling of the organ could not have 

 been the apparent cause of the elevated flow on resto- 

 ration of arterial pressure. It is known that the pH of 

 the cortical substance decreases by 0.3 to 0.4 pH 

 units during partial clamping of the renal artery 

 (237), indicating accumulation of metabolites. 

 Spencer (293) has more recently demonstrated reac- 

 tive hyperemia in the kidney after brief ischemia; flow, 

 measured with a square-wave electromagnetic flow- 

 meter, was increased in dogs after brief clamping of 

 the renal artery. Contrarily, Grupp & Heimpel (118) 

 more often observed small reductions in flow measured 

 in dogs both by direct arterial inflow and venous out- 

 flow following 1 to 7 min of ischemia. In 5 of 26 dogs 

 an increase averaging 16 per cent (maximum, 32%) 

 was seen. Yamada & Astrom (352) did not observe 

 reactive hyperemia in the kidneys of cats after brief 

 ischemia. Since abundant evidence exists that the 

 kidney, after more prolonged ischemia, releases 

 pressor material, the complexity of this interesting 

 problem is evident. The duration of ischemia looms 

 as an important variable. 



intrarenal reflexes. Extrinsic reflexes are not 

 necessary for the manifestation of autonomy, and no 

 afferents from renal baroreceptors or chemoreceptors 

 exist according to Page & McCubbin (239). But the 

 presence of intrarenal autonomic ganglia were ap- 

 parently confirmed pharmacologically: nicotine and 

 dimethylphenylpiperazinium iodide (DMPP) stimu- 

 lated ganglia and caused the discharge of pressor 

 amines. Page and McCubbin have suggested this as a 

 possible mechanism in autoregulation. Since ganglio- 

 plegic and sympatholytic agents have been said to 



