HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



DCA-treated rats using inulin to estimate water 

 distribution. Unfortunately, he analyzed only skeletal 

 and cardiac muscle and hence his report of an absence 

 of correlation must be treated cautiously. Despite his 

 own rather negative conclusion, if we assume that his 

 methods can only distinguish extremes and not 

 transitional stages, his tables show several striking 

 features. Blood pressure in the control-adrenal- 

 ectomized group averaged 86 mm Hg, while the 

 adrenalectomized saline-treated group reached 114 

 mm Hg. The two groups attaining the highest 

 pressure were likewise adrenalectomized and received 

 either DCA-saline or DCA-saline-cortisone and had 

 average blood pressures of 1 9 1 and 221 mm Hg, 

 respectively. Both Na» and Na, values were highest 

 in these groups and the Na /Na, gradients lowest. 

 Again, K„ was lowest in both these groups, while K, 

 did not fit any pattern. The value for K„ is perhaps 

 particularly important, since it has also been reported 

 as a finding in the accelerated phase of essential 

 hypertension in man (111, 151). Low levels of serum 

 Na have also been noted at this stage of the disease 

 (46). 



Woodbury & Koch (211) also noted in the rat that 

 DCA and aldosterone produce an increase in skeletal 

 muscle Na which, judging by measurements of 

 chloride space, is largely intracellular and represents 

 an increase in Na,. Potassium was little altered. 

 Unfortunately, blood pressure was not measured. 

 Ferrebee et al. (62), using more laborious techniques, 

 had long ago shown that DCA in the dog caused a 

 gain in Na, at the expense of K,. Cier and co-workers 

 (29) and Gross & Schmidt (99) also claimed that 

 DCA increases Na, in skeletal muscle. 



Insofar as blood pressure regulation is concerned 

 it is more important to attempt to estimate the effect 

 of DCA on Na and K. in a representative of vascular 

 tissue. The aorta has so far been the only tissue 

 amenable to study and here, by and large, the 

 evidence points the same way. The classic and most 

 quoted paper in this field is that of Tobian & Binion 

 (196), who reported an increase in both Na and K 

 in the aorta of rats made hypertensive with DCA. 

 From estimates of the extracellular space (based on 

 chloride measurements) they believed that most of 

 the increase represented a true intracellular gain. 

 Tobian & Redleaf (199, 200) reaffirmed these 

 findings in later studies. 



Daniel & Dawkins (40) claimed that aorta electro- 

 lyte changes demonstrable in early DCA hypertension 

 disappeared later in the disease. In early hypertension 

 they noted a tendency for a gain in Na, but, more 



significantly, for K depletion in hypertensive rats 

 under treatment compared with normotensive also 

 under treatment. Most recently, Laszt (133) also 

 reported a gain in aorta Na following DCA treat- 

 ment. 



By and large it would seem that DCA causes a gain 

 in Na in both skeletal muscle and in aorta in the rat; 

 a goodly part of this gain probably represents a true 

 intracellular increase, but with the methods so far 

 used it is difficult to assess just how much is actually 

 intracellular. The gain in Na is apparently not 

 accompanied by a parallel gain in water, so we are 

 fairly safe in inferring from all authors that intra- 

 cellular Na concentration, Na„ is elevated. All reports 

 uniformly fail to provide us, however, with simul- 

 taneous estimates of Na, of the aorta and Na„ of the 

 medium, which is a crucial piece of information. This 

 same lack of information tends to nullify Laszt's 

 claim (133) that blood pressure cannot be related to 

 the total Na content of the aorta. In our opinion, it 

 would be exceptional if blood pressure could indeed 

 be related to one such simple parameter as that. 



Other hypertensive states. We have considered DCA 

 separately because of its obvious effects on electrolvte 

 metabolism which might perhaps be considered to 

 make it a special case. We turn now to a more general 

 review of the findings for Na and K analysis in a 

 divergent series of conditions united only by the fact 

 that a sustained hypertension is a common feature. 



Ledingham (139) has recently reviewed this and 

 decided that the onlv common feature in these varied 

 states is the elevated blood pressure itself. His negative 

 view is based on his findings in hvpertension induced 

 by DCA, cortisone, renal arterv constriction, and 

 bilateral nephrectomy (136-138). As described above, 

 he may have overemphasized the negative aspects of 

 his data. It is unfortunate too that this conclusion 

 should have been arrived at without any attempt to 

 measure electrolytes and water in vascular tissue. 



In their original report Tobian & Binion (196) 

 considered renal as well as DCA hypertension in the 

 rat. Aorta Na and K were both elevated following 

 renal constriction in rats developing hypertension 

 compared to animals remaining normotensive after 

 the same operation. Tobian (192) extended this work 

 by using a low sodium diet to control the blood 

 pressure rise of animals with renal constriction and 

 found the changes directly related to the presence or 

 absence of hypertension. 



More recently Tobian & Redleaf (200) found that 

 rats with post-DCA sustained hypertension, with 

 adrenal regeneration hvpertension, and with the 



