EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



"43 



tonus known to occur in gut and urinary bladder 

 during potassium deficiency (72, 170, 210). An ade- 

 quate K intake was also shown to be essential for the 

 development of DC. A hypertension although, unlike 

 the effect of Na, an excessively high K intake does 

 not accelerate the process (68, 169). In later studies, 

 these authors concluded that the effect of varying the 

 K intake depends on its simultaneous relation to the 

 Na intake and that the development of hypertension 

 depends on a high K Na ratio (167, 169). This 

 important theme will recur in our later discussion. 

 Perera (158) confirmed the basic observation by show- 

 ing that essential hypertension in man could be re- 

 duced by a low K diet, although this was not a practi- 

 cable therapy. 



EFFECTS OF VARYING Na AND K INTAKE OR LOSS ON 



blood pressure. Sapirstein and associates first re- 

 ported in 1950 (172) that rats given various hyper- 

 tonic NaCl solutions to drink develop an arterial 

 h\ pertension after a latency of 1 to 4 weeks. This was 

 confirmed by Toussaint et al. (201) and extended by 

 Meneely and his collaborators (151, 152) who showed 

 that the rise in blood pressure in such salt fed animals 

 is proportional to their salt inake. A latter report from 

 this same laboratory (150) pointed out that the effect 

 of adding NaCl to the diet can be partly offset by a 

 simultaneous increase in K as well. From this, they 

 suggested that the blood pressure rise is dependent on 

 an increase in the Na K ratio. This is diametrically 

 opposite to the work of M. Friedman and co-workers, 

 cited above, which implicated a high K/Na ratio. 



Fregly (71) has sharply underlined the importance 

 of salt as a determinant of vascular resistance. He has 

 recently produced hypertension in the adrenalecto- 

 mized salt-fed rat and has shown the relation of the 

 blood pressure rise to the amount of salt ingested. 

 Vick et al. (203) found that vascular sensitivity, meas- 

 ured as the response of the aorta strip to epinephrine, 

 increased in rats after 10 to 15 weeks of high salt 

 feeding. 



The idea that an excessive intake of salt may itself 

 be a sufficient etiological factor in essential hyper- 

 tension has been staunchly supported. In an extensive 

 series of studies Dahl and his colleagues (36-38) have 

 attempted to relate the incidence of hypertension in 

 man to his salt-eating habits. Others have studied 

 areas of reputedly high or low salt intake in order to 

 relate the incidence of hypertension to the dietary 

 habits of the inhabitants (176, 194). So far, however, 

 the evidence that Na intake plays a primary etio- 

 logical role is still shaky. 



A serious deficiency in Na may occur naturally 

 during exposure to excessive heat; the advance of the 

 deficiency is associated with vascular collapse (100). 

 Excessive salt depletion for therapeutic purposes may 

 produce a similar picture (175). In the rat, acute Na 

 depletion may be readily induced by equilibrating an 

 intraperitoneal isosmotic mannitol or sucrose solution 

 with the extracellular compartment. Such a depletion 

 is always accompanied by hypotension (unpublished 

 observation). 



Although the prolonged intake of large amounts 

 of K does not affect the blood pressure of the normo- 

 tensive rat, K restriction is an effective hypotensive 

 procedure (66). The depressor effect depends on the 

 associated Na intake, for it does not occur in the 

 presence of a low, but only with a normal to high 

 intake (67). Such K-deficient hypotensive rats show a 

 marked decrease in pressor response to epinephrine, 

 norepinephrine, angiotensin, and renin (168). Both 

 basal blood pressure and reactivity are rapidly re- 

 stored by KC1 given subcutaneously (72). 



These highlights selected from an extensive litera- 

 ture show the limitations of this type of approach. 

 They also show, however, that sodium and potassium 

 can be implicated in the regulation of blood pressure 

 and that sodium in particular plays some kind of 

 critical role in hypertension. Unfortunately, too many 

 steps intervene in the processes to permit any kind of 

 valid interpretation. Even as far as this type of infor- 

 mation is concerned we are faced with a major omis- 

 sion, for there is no assessment of the possible role of 

 water in relation to salt intake. Sapirstein (171), in an 

 attempt to reconcile the conflicting evidence, has 

 drawn attention to the importance of water in the 

 renal handling of electrolytes. It is evident that ani- 

 mals given various salt solutions to drink are con- 

 fronted in each case with a fixed ratio of salt to water, 

 and an ensuing rise in blood pressure may reflect 

 either the increased salt ingestion or the inability of 

 the animal to make an adjustment in its water intake. 

 Similarly, in states involving salt loss, any speculation 

 must also take into account the simultaneous changes 

 in water distribution. McC.ance & Morrison (143) 

 have pointed out this unsatisfactory aspect of experi- 

 ments which do not distinguish between salt and 

 water as separate variables. 



Evidence from Studies of Tension or Reactivity 

 of Vascular or Analogous Tissue 



EFFECTS OF MANIPULATION OF Na IN THE MEDIUM. 



There is consistent evidence that the exposure of 



