EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



i '39 



By far the major diffusible ion concerned is K.+ and 

 so we may write as a first approximation : 



m F (K% 



where E„, is the potential at equilibrium across the 

 membrane and i, inside, o, outside. Concentrations 

 are usually written but activities, as shown, are more 

 precise. 



The movements of Na+ and Cl~ are essentially 

 quite limited; yet, to the extent that they are perme- 

 able, their distribution must also contribute to the 

 over-all transmembrane potential. Goldman (92) has 

 therefore proposed a constant field equation : 



. RT s <«*>! * l>(Na*Jj * P<Cr) 

 m ' F " (K%+ p(No% * ptcDj 



Bv convention E„, is regarded as positive. The symbol, 

 p, expresses the permeability of the ion relative to 

 A' + taken as unity, influx and efflux being considered 

 separately. This equation may or may not be entirely 

 correct but it is applicable to our purpose, since it 

 takes into account the contributions of ions other 

 than K+ and their relative mobilities. 



Special Properties of the Physiologically Important Ions 



The particular role of Na + and K+ has already been 

 described. They are the major bulk ions of the body 

 and, in fact, the maintenance of their distribution 

 may consume a major share of the body's energy. 

 Their role has been the subject of comprehensive 

 monographs (61, 202). 



Calcium and magnesium, belonging to Group 2 of 

 the periodic table, have in their outer orbital shell 

 two electrons which are given up readily in solution. 

 They may, and probably do, participate in the phe- 

 nomena described above, but they are also particu- 

 larly important in enzymatic processes. They are far 

 more readily complexed than either sodium or potas- 

 sium. 



Hydrogen and hydroxyl ions are distinguished by 

 their mobility and easy penetrability into and out of 

 cells. Their primary involvement in acid-base equilib- 

 ria needs no comment at this point. 



The physiologically important anions have also 

 been the subject of an extensive monograph (54). 



CLASSIFICATION AND CRITICAL 

 APPRAISAL OF METHODS 



It is not our purpose here to describe all the methods 

 used to study the effects of ions on vascular smooth 

 muscle directly or indirectly. The aim is rather to 

 seek the general principles underlying each approach 

 and to indicate to what extent the methods used can 

 further our understanding. On this basis we can 

 classify the methods broadly into two groups: those 

 in which the experimental variable is the cell environ- 

 ment and those in which the vascular tension is the 

 manipulated variable. 



Studies of Vascular Smooth Muscle Tension Associated 

 with Manipulation of the Milieu 



In these studies the ionic milieu or environment of 

 the cells has been manipulated in vivo by varying the 

 dietary salt intake or by loading with various salts 

 given by stomach tube, by infusion, or by injection. 

 In this group we have, too, studies of the effects of 

 hormones known to affect salt metabolism and in 

 vitro studies in which the medium has been directly 

 manipulated. Obviously, the more prolonged the 

 treatment and the more general its effects, the more 

 difficult it is to pin down any direct relation between 

 treatment and vascular smooth muscle tension. Even 

 so, all approaches must be examined if we are not to 

 lose sight of important clues 



The effects of these manipulations, of varying de- 

 grees of remoteness from the target, have been as- 

 sessed by three principal methods. 



MEASUREMENT OF DIASTOLIC BLOOD PRESSURE. Since a 



major determinant of the diastolic blood pressure is 

 the peripheral vascular resistance this approach has 

 some limited value. The results can always be attacked 

 on the grounds that a change may indicate an effect 

 on cardiac output, on blood viscosity, or on blood 

 volume, etc., rather than on peripheral resistance. 

 Such studies have value, however, if they correlate 

 well with other more direct approaches. Experiments 

 of this type in the rat suffer still more seriously from 

 the fact that most of the indirect methods do not 

 measure diastolic blood pressure at all but some 

 mixed level which approximates the mean pressure. 



MEASUREMENT OF PERIPHERAL RESISTANCE IN RE- 

 GIONAL vascular beds. This approach is necessarily 

 confined to studies of the effects of fairly rapid changes 

 in the milieu. Within this limitation, it can be highly 



