EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



• ' 59 



pH as an invariant than with noting and interpreting 

 the effects of changes. 



Schuler (177) measured the tension of mesenteric 

 and phrenic artery rings while shifting pH to either 

 side of normal. He found that tonus increased in both 

 cases. Tobian et al. (198), using the spiral aorta strip 

 of the rat, found that the contractile response to 

 norepinephrine was maximal at relatively higher pH 

 and minimal at lower. It seems to us that nowhere is 

 the duration of immersion or exposure to the altered 

 environment more important than in studies of the 

 effect of H ions. Reference to table 2 will remind us 

 of the extremely high mobility of H + and the ease with 

 which it penetrates the membrane. 



Rogers & Fenn (166) have shown that H + added 

 to the medium exchanges rapidly with K + and Na + 

 of cells. More recently, Saunders et al. (173) have also 

 shown a partial replacement of K, + with H,+ during 

 dietary potassium depletion. At equilibrium, then, 

 an original alteration in medium pH is replaced by an 

 altered Na + and K + distribution. Duration of exposure 

 must then be a critical variable. With this in mind, 

 we can now examine the findings of workers using in 

 vivo preparations. Technically, all the procedures to 

 be quoted are beyond reproach as far as they go. 



Burget & Visscher (23) showed a nice decrease in 

 epinephrine response of the pithed cat proportionate 

 to a stepwise fall in pH. This accords with Tobian et 

 al. (198). Fleisch et al. (63) used good techniques to 

 measure flow and pressure and found that a fall in 

 pH of as little as 0.05 caused generalized vasodilata- 

 tion. 



More recent studies using the technique of con- 

 trolled perfusion of a vascular bed are conflicting. Deal 

 & Green (45), like Kester et al. (127) earlier, reported 

 that solutions on the acid or alkaline side of physio- 

 logical neutrality increased blood flow to limb mus- 

 cles, indicating peripheral vascular relaxation. Skin 

 vessels, however, showed a decrease in resistance as 

 pH fell and an increase as pH rose. Fleishman et al. 

 (64) showed that the picture is complicated by the 

 fact that small vessel segments constitute independent 

 resistances the magnitudes of which may actively 

 vary in opposite directions. The net effects were 

 dilatation of small vessels with an acute fall in pH and 

 constriction with a rise in pH. Emanuel et al. (57) 

 also reported that an acute rise in pH caused an in- 

 creased peripheral vascular resistance through the 

 renal vascular bed. 



Clearly, we are in no position yet to draw any sort 

 of general conclusions except that H ion effects are 

 interwoven with those of Na + and K + . 



10 



10 



20 



20 10 20 



TIME IN MINUTES 

 fig. 1 1 . Average effects of pH change upon total and seg- 

 mental vascular resistances in the nerve intact, nerve blocked 

 and nerve blocked phentolamine dog forelimb. [From Fleish- 

 man et al. (64).] 



ROLE OF ANIONS IN VASCULAR 

 SMOOTH MUSCLE TENSION 



There is a great need for systematic study in this 

 field. So far, although anions have been considered 

 from time to time, they have been studied only to 

 underline the effect of their associated cations. No 

 approach to this problem will really make much sense, 

 however, until an acceptable basic model for the role 

 of cations in the regulation of vascular tension is pre- 

 sented. This model need not be the final one as long 

 as it provides a good rational framework. We hope to 

 present such an integrated view in the theoretical 

 discussion to follow. 



THEORETICAL INTERPRETATIONS 



A rational theoretical interpretation of the available 

 evidence is now quite possible and has been attempted 



