EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



"49 



increase in both Na, and K.,. We shall deal with the 

 quantitative aspects of this type of shifi later. 



effects of K. infusions. Attempts to link the effects 

 observed in vitro to in vivo responses of vascular 

 tissue have necessarily been limited in scope. This 

 again reflects the technical problems limiting such 

 exploration. 



Mathison (149) long ago produced what is still one 

 of the best pieces of work on this subject. He injected 

 a few milliliters of M/7 (isotonic) KC1 into the arterial 

 circulation of the cat. A rise in blood pressure followed 

 at once; this was also obtained in the decerebrate, 

 spinal, or spinal-pithed animal. The effect was not 

 of cardiac origin and was only partly due to excitation 

 of vasomotor centers, since a considerable rise of 

 pressure was still obtained after ergotoxine. This 

 author paid careful attention to tonicity, anion 

 control, and pH. He pointed out also that peripheral 

 vascular relaxation rather than constriction followed 

 the injection of less concentrated solutions beginning 

 at mil Hoff et al. (115) obtained much the same 

 result. 



Hazard & Quinquaud (108) carried out an ex- 

 ceedingly nice pharmacological study of the pressor 

 effect of intra-arterially injected K.C1. They showed 

 that a large part of the effect was due to adrenal 

 medullary discharge. Then, using a series of blocking 

 agents, they came to the conclusion that a significant 

 part of the vasoconstrictive action of K was directly 

 exerted on vascular smooth muscle. 



McKeever and associates (146) perfused the left 

 coronary in the dog with blood from a donor animal, 

 interposing a constant output pump in the line 

 (cf 101). K.C1 was then added at constant rate to 

 raise plasma K from 2 to 20 meq per liter. Except at 

 the very lowest concentrations the infusions produced 

 a transient dilatation of large and small arterial 

 segments lasting for about 1 min, followed by a more 

 sustained constriction. Still higher concentrations were 

 entirely constrictive, but the degree to which an 

 adrenal discharge may have contributed was not 

 assessed. 



Emanuel et al. (58) have carried out a careful 

 analysis of the changing pattern of resistance in the 

 different segments of the dog forelimb during infusion 

 of K. salts and have correlated their findings with 

 systemic and local measurements of serum Na and K. 

 Small vessel resistance decreased at all infusion rates. 

 By contrast, arterial resistance did not change at 

 lower rates and then, as the rate increased, gradually 

 began to show an increase. The net effect of these 



changes was an over-all fall in resistance at low rates 

 and a rise at higher ones. The primary phenomenon 

 held for increases in serum K up to about 8 meq 

 per liter, at which point the secondary net constrictive 

 effect appeared. The arterial constrictive phase may 

 be in large part related to adrenal discharge. These 

 results were similar for the chloride, nitrate, lactate, 

 and acetate. They applied equally well to the renal 

 vascular bed (178). Even these moderate elevations 

 of K„ reduced the sensitivity of the peripheral vas- 

 culature to challenging doses of pressor and depressor 

 agents. 



The work of this group satisfactorily explains the 

 phase of falling peripheral vascular resistance noted 

 by all authors who have infused small amounts of 

 KC1. It also shows that K does not produce smooth 

 muscle vasoconstriction in the physiological range 

 and agrees in this with in vitro studies. It leaves 

 unexplored, and correctly so, the effect of high, 

 unphysiological amounts of K which are vasocon- 

 strictive in vitro. This latter point has great theoreti- 

 cal importance if a change in membrane potential 

 is involved in peripheral vasoconstriction. Un- 

 fortunately, the experimenter cannot explore the 

 problem in vivo, for although high K infusions do not, 

 like Na, raise problems of osmotic pressure they do 

 produce adrenal, cardiac, and nervous effects which 

 presently defy rational interpretation. 



Speaking critically, the perfusion of regional 

 vascular beds is not a totally satisfactory approach to 

 the problem. Technically, many of the procedures 

 give detailed information concerning the responses of 

 each segment of the vascular bed and for this are 

 most satisfactory. The problem resides not in this 

 facet of the approach but in the attempt to alter a 

 single variable in the medium while still perfusing 

 with whole blood. Such a situation cannot be fully 

 controlled. Using the Na and K electrodes we have 

 found many times that the solution we thought was 

 presented to the cells was not the same as the solution 

 the cells actually met. To interpret such perfusion 

 data fully requires information about the Na, K, and 

 Ca levels actually attained, together with an estimate 

 of pH. 



Evidence from Meamrement of Xa and A in 

 Relation to Blood Pressure 



measurement of Na and K in chronic hypertension 

 or hypotension. Deoxycorticosterone (DC A) hyper- 

 tension. Ledingham (137, 138) studied the relation of 

 Na and K. partition to blood pressure in a series of 



