HIE RENAL CIRCULATION 



1491 



eliminate the mechanism of homeostasis [Brull et al. 

 (38)], the possibility of such an intrarenal reflexogenic 

 mechanism should be weighed, although possible 

 afferent pathways resembling an axon reflex (den- 

 dritic mechanoreceptors or stretch receptors) remain 

 to be demonstrated. The results of Brull et al., who 

 argued for an intrarenal reflex mechanism, were some- 

 what sporadic and complicated by the fact that some 

 of their perfusion pressures after drug treatment were 

 high enough to exceed the normal range of autonomy. 

 Intrarenal sympatholysis with Dibenzyline (331) and 

 phentolamine (124), tested by abolishing the vasocon- 

 striction produced by DMPP, did not abolish auto- 

 regulation. 



Procaine injected directly into the renal artery will 

 abolish autoregulation, but this could be an effect 

 directly on the smooth muscle of the arterioles. How- 

 ever, Waugh & Shanks (331) claimed that with pro- 

 caine concentration of only 50 ng per 100 ml of 

 perfusate, anesthesia of intrarenal nervous elements 

 was achieved without concomitant removal or ap- 

 preciable depression of vascular smooth muscle re- 

 sponses to direct stimuli. This prevented the 

 vasoconstrictor response of DMPP, but the prepara- 

 tion remained sensitive to small doses of epinephrine 

 or barium chloride. When pressure was elevated by 50 

 per cent, flow increased only 13 per cent. Further- 

 more, yohimbine, an adrenergic blocking agent, in 

 concentrations which caused nearly complete intra- 

 renal sympatholysis (as judged by blockade of large 

 test responses to the ganglionic stimulant DMPP and 

 to epinephrine) did not depress autoregulation (331)- 



Twenty times greater perfusate concentrations of 

 procaine (0.1 g/100 ml) were shown by Waugh and 

 Shanks to abolish autoregulation. In a typical experi- 

 ment, renal flow increased 64 per cent per 50 per cent 

 increase in arterial pressure. The intense renal vaso- 

 constriction normally evoked by intra-arterial injec- 

 tions of 1 /ig epinephrine and 2.5 mg of barium 

 chloride was largely prevented by the higher concen- 

 trations of procaine. It is likely that results obtained 

 by Ochwadt (233) and Weiss et al. (333) with com- 

 parable dosage of procaine are also the result of 

 marked direct depression of smooth muscle activity. 



In summary, the intricacies of distinguishing be- 

 tween abolition of an intrarenal neurogenic com- 

 ponent and direct effects on smooth muscle by 

 pharmacological agents are apparent. It would 

 appear, nevertheless, that the evidence offered by 

 Waugh and Shanks weighs heavily against a nervous 

 component. 



the viscosity theorv. Foremost proponents of this 

 theory are Pappenheimer & Kinter (159, 160, 240) 

 with their cell separation hypothesis, championed 

 by Winton (343, 344). The details are so well known 

 that only a brief review is necessary. In this theory, the 

 interlobular arteries and afferent arterioles act as 

 vessels specially developed to promote plasma 

 skimming and stripping. Streamlining of erythrocytes 

 leaves a core of cells to supply the outer cortical 

 glomeruli. A gradient of red cell concentration would 

 develop, with low cell hematocrit in the deep 

 glomeruli, and high hematocrit in the outer cortical 

 glomeruli. They suppose that the red cells after 

 traversing the glomeruli and efferent arterioles have 

 access to special through channels communicating 

 directly to interlobular veins, leaving a plasma-rich 

 component of the blood to supply the peritubular 

 vascular bed. 



Pappenheimer and Kinter believe that the above 

 scheme offers an explanation for the low dynamic 

 hematocrit of the kidney, since the red cells move 

 through the hypothetical shunts faster than the 

 plasma, so that the instantaneous hematocrit of the 

 total renal blood content would be less than the ar- 

 terial hematocrit value. Support for this was offered 

 by the experimental demonstration in cats that low- 

 ered arterial pressure (less streamlining, hence less 

 cell separation) showed higher intrarenal hematocrit. 



Autoregulation is brought about by the change in 

 viscosity, increasing in turn resistance to blood flow 

 resulting from hemoconcentration as the blood pro- 

 ceeds to the outer cortex. Such a mechanism could 

 keep total flow constant as a function of the level of 

 arterial pressure. Added facets that are important 

 are as follows: reduction in hematocrit of the per- 

 fusing fluid caused remission of autoregulation, and 

 development of a linear P:F relationship, as the 

 theory would demand (160). Implicit in the theory is 

 that a gradient of filtration rate should occur based 

 on the hematocrit distribution, i.e., the inner 

 glomeruli receiving the higher volume of plasma 

 should have the higher filtration rate. A mechanism 

 for autonomy of glomerular filtration rate is offered, 

 for with reduced blood pressure less stripping would 

 occur, so that peripheral glomeruli would have a 

 relative increase in filtration rate, despite the increase 

 in the inner glomeruli. 



Incomplete extraction of PAH and Diodrast in dog 

 and man (0.75 to 0.9 respectively), which decreases 

 under a variety of experimental conditions, is ex- 

 plained by the fact that blood passing through shunts 

 is unavailable for extraction. The separation process, 



